|
1
|
Pavan Sai Kumar Rao D, Patro S, Sharma V, Choudhary A, Desale S, Nath P. Diagnostic Accuracy of Red Cell Distribution Width to Platelet Ratio for the Prediction of Liver Fibrosis in Patients With Chronic Liver Disease From Eastern India. Cureus 2025; 17:e82014. [PMID: 40352011 PMCID: PMC12065511 DOI: 10.7759/cureus.82014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Accepted: 04/10/2025] [Indexed: 05/14/2025] Open
Abstract
Background Early diagnosis of liver cirrhosis in patients with chronic liver disease (CLD) can help delay/prevent complications and thereby improve survival. The currently available diagnostic modalities for the non-invasive assessment of hepatic fibrosis, especially FibroScan, are costly and not widely available, whereas various non-invasive scores for the assessment of fibrosis are cumbersome. Hence, we aimed to develop an easy and simple score for predicting cirrhosis in patients from Eastern India suffering from CLD with a better diagnostic accuracy. Methodology This cross-sectional, observational study was conducted between September 2019 and September 2021 in East India. Our study participants were patients who had CLD of etiologies such as alcohol-related liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis B, chronic viral hepatitis C, primary biliary cholangitis, and autoimmune hepatitis, who had undergone FibroScan of the liver. All demographic details were noted, and the patients were subjected to physical examination, followed by hematological as well as biochemical investigations, including liver function tests. Non-invasive scores (such as aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 score (FIB-4) and red cell distribution width (RDW) to platelet ratio (RPR)) were computed, and their diagnostic accuracy for prediction of advanced fibrosis and cirrhosis were evaluated by receiver operating characteristic curve (ROC curve) analysis with comparison of area under the ROC curves. Pearson correlation and logistic regression analysis were also performed to study the association of these scores with advanced fibrosis and cirrhosis. Results The area under the ROC (AUROC) curve of the APRI score, FIB-4 score, RPR, and RPR × AST for prediction of advanced liver fibrosis was 0.817, 0.799, 0.706, and 0.811, respectively. Similarly, the AUROC of the above scores for the prediction of cirrhosis was 0.889, 0.858, 0.797, and 0.898. However, the product of RPR and AST was superior than APRI and FIB-4 for predicting cirrhosis. An RPR × AST value above the cut-off of 4.818 can help predict liver cirrhosis with 85.7% sensitivity and 85.5% specificity. Pearson correlation and logistic regression analysis also proved the association of these scores with liver fibrosis. Conclusions RPR is a simple, inexpensive, and easily available marker for predicting liver cirrhosis. Nevertheless, the variable RPR × AST can predict liver cirrhosis in patients with CLD with even greater diagnostic accuracy.
Collapse
Affiliation(s)
- D Pavan Sai Kumar Rao
- Department of Medical Gastroenterology, Gleneagles BGS Global Hospitals, Bengaluru, IND
| | - Shubhransu Patro
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Vibha Sharma
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Arushi Choudhary
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Shubham Desale
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Preetam Nath
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| |
Collapse
|
|
2
|
Yu H, Yu H, Sun Y, Wang FS, Lu Y. Chinese expert consensus on clinical management of hepatopathy-related thrombocytopenia (2023 edition). Hepatol Int 2025; 19:70-86. [PMID: 39907913 DOI: 10.1007/s12072-024-10755-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 11/09/2024] [Indexed: 02/06/2025]
Abstract
Hepatopathy-related thrombocytopenia refers to a reduction in platelet count caused by liver disease or its treatment. The incidence of this condition is correlated with the duration and severity of liver disease. The direct impact of thrombocytopenia on the clinical outcome of patients with liver disease is an increased risk of bleeding. In addition, the indirect effect involves delays or discontinuation of treatment due to the potential risk of bleeding. The pathophysiological mechanisms of hepatopathy-related thrombocytopenia include reduced platelet production, abnormal distribution, increased destruction or consumption, and so on. Current treatment strategies targeting different mechanisms include thrombopoietic agents, surgery, immunosuppressants, and platelet transfusion. However, their clinical application lacks standardization. The National Clinical Research Center for Infectious Diseases organized experts to discuss and develop this consensus to enhance the clinical management level of hepatopathy-related thrombocytopenia in China. The experts focused on aspects of diagnosis, classification, and choosing the best treatment plans based on the most recent research in the field.
Collapse
Affiliation(s)
- Hang Yu
- Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hongli Yu
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yao Sun
- Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fu-Sheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China.
| | - Yinying Lu
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China.
| |
Collapse
|
|
3
|
Ang SP, Chia JE, Iglesias J, Usman MH, Krittanawong C. Coronary Intervention Outcomes in Patients with Liver Cirrhosis. Curr Cardiol Rep 2025; 27:2. [PMID: 39754700 PMCID: PMC11700054 DOI: 10.1007/s11886-024-02163-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/20/2024] [Indexed: 01/06/2025]
Abstract
PURPOSE OF REVIEW This review assesses the outcomes of coronary interventions in patients with liver cirrhosis and coronary artery disease (CAD), focusing on the clinical challenges posed by cirrhosis-related hemodynamic and coagulopathic changes. It highlights essential considerations for managing these patients, who have an increased risk of adverse events during coronary procedures. RECENT FINDINGS Recent studies have shown that patients with liver cirrhosis undergoing PCI experience significantly higher mortality rates compared to non-cirrhotic patients, particularly in the context of STEMI and NSTEMI. Coagulopathy and thrombocytopenia increase the risk of bleeding and vascular complications during interventions. Radial access has been suggested as a safer alternative to femoral access in these patients due to reduced bleeding complications. Additionally, contrast-induced nephropathy (CIN) is a prevalent risk, with cirrhotic patients demonstrating higher rates of acute kidney injury post-PCI. Preventive strategies such as minimizing contrast exposure and utilizing intravascular ultrasound (IVUS) are recommended. Managing CAD in cirrhotic patients requires careful consideration of their unique pathophysiological state. Higher in-hospital mortality, bleeding risks, and vascular complications necessitate tailored procedural strategies, such as radial access and contrast minimization. The balance between thrombotic and bleeding risks is critical in decision-making, with IVUS and hydration strategies being promising approaches. Further research is required to optimize treatment protocols and improve long-term outcomes for this high-risk population.
Collapse
Affiliation(s)
- Song Peng Ang
- Department of Medicine, Rutgers Health/Community Medical Center, Toms River, NJ, USA.
| | - Jia Ee Chia
- Department of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Jose Iglesias
- Department of Medicine, Rutgers Health/Community Medical Center, Toms River, NJ, USA
- Department of Medicine, Hackensack Meridian School of Medicine, Nutley, NJ, USA
| | | | | |
Collapse
|
|
4
|
Su M, He M, Liu JL, Yang WC, Wang JJ, Guo C, Fu YM, Wang CY, Li S, Ji D, Chen HY. The therapeutic effect of leucogen in treating alcoholic liver cirrhosis with thrombocytopenia or leukopenia. Ann Saudi Med 2025; 45:9-17. [PMID: 39929792 PMCID: PMC11810874 DOI: 10.5144/0256-4947.2025.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 12/07/2024] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Thrombocytopenia and leukopenia are common complications of alcoholic liver cirrhosis (ALC) and are associated with an increased risk of bleeding, infection and mortality. OBJECTIVES Evaluate the effectiveness and safety of leucogen, a cysteine derivative that increases platelet (PLT) and white blood cell (WBC) counts in ALC patients. DESIGN Retrospective. SETTING Department of hepatology, general hospital. PATIENTS AND METHODS Patients with ALC who had thrombocytopenia and/or leukopenia were enrolled between 2022 and 2023 and were divided into two groups based on their treatment: the leucogen group (20 mg, three times per day) and the non-leucogen group. MAIN OUTCOME MEASURES The primary endpoint was an increase in PLT or WBC of ≥5% from baseline. SAMPLE SIZE 413 patients (320 patients in the final analysis). RESULTS In this retrospective study, 320 patients were analyzed post-propensity score matching: 160 patients each in the leucogen and non-leucogen groups. Following 3 months of treatment, the leucogen group experienced a median increase in PLT levels of 1.0×109/L versus a decrease of 3.0×109/L in the non-leucogen group (P=.003), and a median increase in WBC counts of 0.1×109/L compared to a decrease of 0.1×109/L (P=.006). The changes in ALT, AST, and TBIL levels were not significantly different between groups. A higher proportion of patients in the leucogen group experienced increases in both PLT (46.9% vs. 32.5%, P=.012) and WBC counts (50.0% vs. 36.2%, P=.018), and 28.1% of patients in the leucogen group had increases in both parameters, compared to 15.6% in the non-leucogen group (P=.01). The leucogen group also demonstrated greater increases in PLT (OR 1.833; P=.009) and WBC counts (OR 1.759; P=.013) compared to the non-leucogen group. The safety profile of leucogen was favorable, with no significant adverse events reported. Leucogen was particularly beneficial for patients younger than 60 years and those with lower baseline ALT and AST levels, showing significant improvements in both PLT and WBC counts in these subgroups. CONCLUSIONS Leucogen effectively increased PLT and WBC counts in patients with ALC, showing a favorable safety profile. LIMITATIONS Retrospective study.
Collapse
Affiliation(s)
- Min Su
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Mengwen He
- From Peking University 302 Clinical Medical School, Beijing, China
| | - Jia-Liang Liu
- From Hospital of North China Electric Power University, Beijing, China
| | - Wu-Cai Yang
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Jian-Jun Wang
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Chang Guo
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yi-Ming Fu
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Chun-Yan Wang
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Shuyao Li
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
- From Peking University 302 Clinical Medical School, Beijing, China
| | - Dong Ji
- From Senior Department of Hepatology, The Fifth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China
- From Peking University 302 Clinical Medical School, Beijing, China
| | - Hong-Yan Chen
- From Hospital of North China Electric Power University, Beijing, China
| |
Collapse
|
|
5
|
Onișor D, Roiban AL, Cernea S. Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Patients-The Relationship with Platelets Indicators. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2091. [PMID: 39768970 PMCID: PMC11676065 DOI: 10.3390/medicina60122091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025]
Abstract
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important chronic liver disease with major health risks, especially in the presence of T2DM, but the pathophysiology of this condition is not fully understood. This study aimed to investigate the platelet hematometric indices in patients with T2DM and MASLD. Materials and Methods: Demographic and medical (including anthropometric) data were collected from 271 participants, from whom blood samples were also drawn in fasting conditions for complete blood count, liver and metabolic panel, ferritin, haptoglobin, creatinine, and fibrosis markers. The correlations of main platelet parameters with clinical and laboratory data were investigated by bivariate and multiple regression analyses. Results: The median platelets number was 235·103/μL, and thus, the study population was divided into two subgroups: with higher and lower numbers (group 1 (mean): 286.38 ± 43.29·103/μL and group 2 (mean): 188.12 ± 39.77·103/μL). Despite similar BMIs, group 2 had higher fatty liver index (FLI) (84.44 ± 18.04 vs. 79.85 ± 17.98; p = 0.0088) and insulin resistance (HOMA-IR: 3.16 ± 1.50 vs. 2.63 ± 1.31; 0.0008), higher direct bilirubin, transaminases, uric acid, and ferritin concentrations. Higher percentages of males and subjects with HOMA-IR values >2.5 were accounted for in this group. In the multiple regression analyses, the platelet count and plateletcrit (PTC) correlated independently with sex, leucocyte count, HOMA-IR, and bilirubin concentrations (p < 0.0001). The platelet distribution width (PDW) was positively correlated with insulin resistance in two separate analyses (β = 0.060; p = 0.0004, and β = 0.052; p = 0.0025), and with GGT, while the mean platelet volume presented a weak but significant positive association with FLI. Patients with higher HOMA-IR had higher PDW and a lower platelet count and PTC. Conclusions: Male patients with T2DM and MASLD had lower platelet count and PTC and larger PDW. Higher insulin resistance was associated with lower platelet count and PTC and higher PDW.
Collapse
Affiliation(s)
- Danusia Onișor
- Department ME2, Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureş, 540142 Târgu Mureş, Romania;
- Gastroenterology Clinic, Mureș County Clinical Hospital, 540103 Târgu Mureş, Romania
| | - Andrada Larisa Roiban
- Diabetes Compartment, Mediaș Municipal Hospital, 551030 Mediaș, Romania;
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu Mureş, Romania
| | - Simona Cernea
- Department M3, Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu Mureş, Romania
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, 540136 Târgu Mureş, Romania
| |
Collapse
|
|
6
|
Gaspar R, Macedo G. Non-Invasive versus Invasive Assessment of Portal Hypertension in Chronic Liver Disease. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:377-387. [PMID: 39633911 PMCID: PMC11614439 DOI: 10.1159/000538484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 03/05/2024] [Indexed: 12/07/2024]
Abstract
Background Cirrhosis is one of the major causes of morbidity and mortality worldwide and the second leading cause of digestive disease mortality. Portal hypertension is the main driver of cirrhosis-related complications such as ascites and variceal bleeding. Portal hypertension is defined as a hepatic venous pressure gradient >5 mm Hg, although it is clinically significant and associated with clinical complications when >10 mm Hg. Summary Therefore, detection of clinically significant portal hypertension (CSPH) in chronic advanced liver disease or compensated cirrhosis is of paramount importance to guide the management of these patients. Key Messages This study aimed at revising the non-invasive and invasive tools for assessment of portal hypertension and risk stratification for CSPH in patients with chronic liver disease.
Collapse
Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology, Centro Hospitalar e Universitário de São João, Porto, Portugal
- Faculty of Medicine of University of Porto, Porto, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology, Centro Hospitalar e Universitário de São João, Porto, Portugal
- Faculty of Medicine of University of Porto, Porto, Portugal
| |
Collapse
|
|
7
|
Crăciun R, Buliarcă A, Matei D, Grapă C, Nenu I, Ștefănescu H, Mocan T, Procopeț B, Spârchez Z. Cirrhosis Progression Is Not Associated with Clinically Significant Alterations in Global Hemostasis Assessed by Thromboelastography. J Clin Med 2024; 13:6614. [PMID: 39518754 PMCID: PMC11546942 DOI: 10.3390/jcm13216614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/26/2024] [Accepted: 11/02/2024] [Indexed: 11/16/2024] Open
Abstract
(1) Background: Cirrhosis is associated with frequent alterations in standard coagulation tests that do not adequately reflect hemostasis. Thromboelastography provides a global assessment of coagulation and evaluates the functional status of clotting factors, fibrinogen, platelets, and fibrinolysis. The study aimed to assess whether liver disease severity leads to progressive alterations in the thromboelastography-based assessment of coagulation. (2) Methods: Consecutive patients with cirrhosis and abnormal standard coagulation tests (at least one of International Normalized Ratio > 2, platelet count < 50 × 103/µL, fibrinogen < 200 mg/dL) were analyzed using native thromboelastography. (3) Results: A total of 106 patients were included, of whom 69 (65.1%) had a normal thromboelastography. While the standard coagulation tests were significantly worse in patients in the Child C group (n = 62, 58.5%) than in patients staged in Child A and B, no significant differences existed between any of the thromboelastography variables. Of the 50 patients (47.1%) with an International Normalized Ratio > 2, only two patients (4%) had features of hypocoagulation, while 26% had features of hypercoagulability on thromboelastography. Patients with a platelet count < 50 × 103/µL had significantly lower platelet function as assessed by thromboelastography, yet only eight patients (20%) met the criteria for platelet transfusion. A thromboelastography-based transfusion protocol might lead to a 94.6% reduction in blood product transfusion indications in a simulation where the included patients would require interventional procedures. (4) Conclusion: Standard coagulation tests showed a poor correlation with thromboelastography. Based on thromboelastography, patients with severe, decompensated liver disease have a preserved hemostasis balance despite abnormal standard coagulation tests. Therefore, standard coagulation tests should not be used to guide the administration of blood products in patients with cirrhosis.
Collapse
Affiliation(s)
- Rareș Crăciun
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (R.C.); (A.B.); (B.P.); (Z.S.)
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
| | - Alina Buliarcă
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (R.C.); (A.B.); (B.P.); (Z.S.)
| | - Daniela Matei
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (R.C.); (A.B.); (B.P.); (Z.S.)
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
| | - Cristiana Grapă
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (R.C.); (A.B.); (B.P.); (Z.S.)
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
| | - Iuliana Nenu
- Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Horia Ștefănescu
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
| | - Tudor Mocan
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
- UBBMed Department, Babeș-Bolyai University, 400084 Cluj-Napoca, Romania
| | - Bogdan Procopeț
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (R.C.); (A.B.); (B.P.); (Z.S.)
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
| | - Zeno Spârchez
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (R.C.); (A.B.); (B.P.); (Z.S.)
- Gastroenterology Clinic, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (H.Ș.); (T.M.)
| |
Collapse
|
|
8
|
Stockhausen S, Kilani B, Schubert I, Steinsiek AL, Chandraratne S, Wendler F, Eivers L, von Brühl ML, Massberg S, Ott I, Stark K. Differential Effects of Erythropoietin Administration and Overexpression on Venous Thrombosis in Mice. Thromb Haemost 2024; 124:1027-1039. [PMID: 37846465 PMCID: PMC11518618 DOI: 10.1055/s-0043-1775965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 08/06/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND Deep vein thrombosis (DVT) is a common condition associated with significant mortality due to pulmonary embolism. Despite advanced prevention and anticoagulation therapy, the incidence of venous thromboembolism remains unchanged. Individuals with elevated hematocrit and/or excessively high erythropoietin (EPO) serum levels are particularly susceptible to DVT formation. We investigated the influence of short-term EPO administration compared to chronic EPO overproduction on DVT development. Additionally, we examined the role of the spleen in this context and assessed its impact on thrombus composition. METHODS We induced ligation of the caudal vena cava (VCC) in EPO-overproducing Tg(EPO) mice as well as wildtype mice treated with EPO for two weeks, both with and without splenectomy. The effect on platelet circulation time was evaluated through FACS analysis, and thrombus composition was analyzed using immunohistology. RESULTS We present evidence for an elevated thrombogenic phenotype resulting from chronic EPO overproduction, achieved by combining an EPO-overexpressing mouse model with experimental DVT induction. This increased thrombotic state is largely independent of traditional contributors to DVT, such as neutrophils and platelets. Notably, the pronounced prothrombotic effect of red blood cells (RBCs) only manifests during chronic EPO overproduction and is not influenced by splenic RBC clearance, as demonstrated by splenectomy. In contrast, short-term EPO treatment does not induce thrombogenesis in mice. Consequently, our findings support the existence of a differential thrombogenic effect between chronic enhanced erythropoiesis and exogenous EPO administration. CONCLUSION Chronic EPO overproduction significantly increases the risk of DVT, while short-term EPO treatment does not. These findings underscore the importance of considering EPO-related factors in DVT risk assessment and potential therapeutic strategies.
Collapse
Affiliation(s)
- Sven Stockhausen
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Badr Kilani
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Irene Schubert
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | | | - Sue Chandraratne
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Franziska Wendler
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Luke Eivers
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Marie-Luise von Brühl
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Steffen Massberg
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| | - Ilka Ott
- Department of cardiology, German Heart Center, Munich, Germany.
| | - Konstantin Stark
- Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
- German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- Walter-Brendel Center of Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
| |
Collapse
|
|
9
|
Gananandan K, Singh R, Mehta G. Systematic review and meta-analysis of biomarkers predicting decompensation in patients with compensated cirrhosis. BMJ Open Gastroenterol 2024; 11:e001430. [PMID: 39182920 PMCID: PMC11404266 DOI: 10.1136/bmjgast-2024-001430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 08/06/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND AND AIMS The transition from compensated to decompensated cirrhosis is crucial, drastically reducing prognosis from a median survival of over 10 years to 2 years. There is currently an unmet need to accurately predict decompensation. We systematically reviewed and meta-analysed data regarding biomarker use to predict decompensation in individuals with compensated cirrhosis. METHODS PubMed and EMBASE database searches were conducted for all studies from inception until February 2024. The study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality of Prognosis Studies framework was used to assess the risk of bias. The meta-analysis was conducted with a random effects model using STATA software. RESULTS Of the 652 studies initially identified, 63 studies (n=31 438 patients) were included in the final review, examining 49 biomarkers. 25 studies (40%) were prospective with the majority of studies looking at all-cause decompensation (90%). The most well-studied biomarkers were platelets (n=17), Model for End-Stage Liver Disease (n=17) and albumin (n=16). A meta-analysis revealed elevated international normalised ratio was the strongest predictor of decompensation, followed by decreased albumin. However, high statistical heterogeneity was noted (l2 result of 96.3%). Furthermore, 21 studies were assessed as having a low risk of bias (34%), 26 (41%) moderate risk and 16 (25%) high risk. CONCLUSIONS This review highlights key biomarkers that should potentially be incorporated into future scoring systems to predict decompensation. However, future biomarker studies should be conducted with rigorous and standardised methodology to ensure robust and comparable data.
Collapse
Affiliation(s)
| | - Rabiah Singh
- UCL Institute for Liver & Digestive Health, London, UK
| | - Gautam Mehta
- UCL Institute for Liver & Digestive Health, London, UK
| |
Collapse
|
|
10
|
Wibawa IDN, Mariadi IK, Somayana G, Sindhughosa D. Efficacy and Safety of Thrombopoietin Receptor Agonist (TPO-RA) in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis. HEPATITIS MONTHLY 2024; 24. [DOI: 10.5812/hepatmon-143200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 05/23/2024] [Accepted: 06/06/2024] [Indexed: 01/03/2025]
Abstract
Context: The TPO-receptor agonist (TPO-RA) has been extensively studied for its use in thrombocytopenia. Objectives: We aimed to systematically analyze the efficacy and safety of TPO-RA in chronic liver disease patients. Methods: The study population consisted of adults with chronic liver disease. The intervention was TPO-RA. The primary outcome was the efficacy of TPO-RA (increase in thrombocyte levels and likelihood of avoiding thrombocyte transfusion pre-operatively), while the secondary outcome was the safety of TPO-RA. The demographics of the study and the usage of TPO-RA medications were used to classify the research. Results: This review consisted of 1529 chronic liver disease patients who received TPO-RA and 911 who received a comparator (placebo or thrombocyte transfusion). The TPO-RA significantly increased thrombocyte levels by 34.59 × 109/L (P < 0.00001). The use of TPO-RA pre-procedure reduced the likelihood of pre-operative platelet transfusion and up to seven days following the scheduled procedure by 88% (P < 0.00001). TPO-receptor agonist was not associated with all-cause mortality (P = 0.77) or an increase in thrombosis events, with a pooled OR of 1.36 (P = 0.43). According to a meta-regression analysis, the population may explain the heterogeneity. Subsequent leave-one-out sensitivity analysis of the thrombocyte level change after TPO-RA revealed that no single study was accountable for the heterogeneity of thrombocyte level changes. Conclusions: The use of TPO-RA increases the thrombocyte levels of chronic liver disease patients and reduces the odds of needing thrombocyte transfusion pre-operatively. TPO-receptor agonist is also safe to use, with no increase in mortality risk or thrombosis risk.
Collapse
|
|
11
|
GAROT P, Morice MC, Angiolillo DJ, Cabau JR, Park DW, Van Mieghem NM, Collet JP, Leon MB, Sengottuvelu G, Neylon A, ten Berg JM, Mylotte D, Tchétché D, Krucoff MW, Reardon MJ, Piazza N, Mack MJ, Généreux P, Makkar R, Hayashida K, Ohno Y, Mochizuki S, Shirai Y, Matsumara R, Jin Y, Webb JG, Cutlip DE, Chen M, Spitzer E, Mehran R, Capodanno D. Defining high bleeding risk in patients undergoing transcatheter aortic valve implantation: a VARC-HBR consensus document. EUROINTERVENTION 2024; 20:536-550. [PMID: 38726720 PMCID: PMC11067726 DOI: 10.4244/eij-d-23-01020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 02/12/2024] [Indexed: 05/14/2024]
Abstract
The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..
Collapse
Affiliation(s)
- Philippe GAROT
- Institut Cardiovasculaire Paris-Sud (ICPS), Hôpital privé Jacques Cartier, Ramsay-Santé, Massy, France
- Cardiovascular European Research Center (CERC), Massy, France
| | - Marie-Claude Morice
- Institut Cardiovasculaire Paris-Sud (ICPS), Hôpital privé Jacques Cartier, Ramsay-Santé, Massy, France
- Cardiovascular European Research Center (CERC), Massy, France
| | - Dominick J. Angiolillo
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Josep Rodés- Cabau
- Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada
- Clínic Barcelona, Barcelona, Spain
| | - Duk-Woo Park
- Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Nicolas M. Van Mieghem
- Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, the Netherlands
| | - Jean-Philippe Collet
- Sorbonne Université, ACTION Study Group, INSERM UMR_S 1166, Institut de Cardiologie, Pitié-Salpêtrière Hospital, Paris, France
| | - Martin B. Leon
- Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA and Cardiovascular Research Foundation, New York, NY, USA
| | - Gunasekaran Sengottuvelu
- Department of Cardiology, Apollo Hospitals, Chennai, Tamil Nadu, India
- Department of Cardiology and Center for Platelet Function Research, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Antoinette Neylon
- Institut Cardiovasculaire Paris-Sud (ICPS), Hôpital privé Jacques Cartier, Ramsay-Santé, Massy, France
- Cardiovascular European Research Center (CERC), Massy, France
| | | | - Darren Mylotte
- Galway University Hospital and University of Galway, Galway, Ireland
| | - Didier Tchétché
- Groupe CardioVasculaire Interventionnel, Clinique Pasteur, Toulouse, France
| | - Mitchell W. Krucoff
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA
| | - Michael J. Reardon
- Department of Cardiovascular Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Nicolo Piazza
- McGill University Health Centre, Montreal, QC, Canada
| | | | - Philippe Généreux
- Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ, USA
| | - Raj Makkar
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Kentaro Hayashida
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
| | - Yohei Ohno
- Department of Cardiology, Tokai University School of Medicine, Isehara, Japan
| | | | | | | | - Yu Jin
- Notified body 1639, SGS, Antwerp, Belgium
| | - John G. Webb
- Department of Cardiology, St. Paul’s Hospital and University of British Columbia, Vancouver, BC, Canada
| | - Donald E. Cutlip
- Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA and Baim Clinical Research Institute, Boston, MA, USA
| | - Mao Chen
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Ernest Spitzer
- Thoraxcenter, Erasmus University Medical Center, and Cardialysis, Clinical Trial Management and Core Laboratories, Rotterdam, the Netherlands
| | - Roxana Mehran
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Davide Capodanno
- Cardiovascular European Research Center (CERC), Massy, France
- Cardio-Thoracic-Vascular Department, Centro Alte Specialità e Trapianti, Catania, Italy
| |
Collapse
|
|
12
|
Tiucă OM, Morariu SH, Mariean CR, Tiucă RA, Nicolescu AC, Cotoi OS. Predictive Performances of Blood-Count-Derived Inflammatory Markers for Liver Fibrosis Severity in Psoriasis Vulgaris. Int J Mol Sci 2023; 24:16898. [PMID: 38069218 PMCID: PMC10707279 DOI: 10.3390/ijms242316898] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/24/2023] [Accepted: 11/26/2023] [Indexed: 12/18/2023] Open
Abstract
Psoriasis is an immune-mediated, chronic disorder that significantly alters patients' quality of life and predisposes them to a higher risk of comorbidities, including liver fibrosis. Various non-invasive tests (NITs) have been validated to assess liver fibrosis severity, while blood-count-derived inflammatory markers have been proven to be reliable in reflecting inflammatory status in psoriatic disease. The fibrosis-4 (FIB-4) index became part of the newest guideline for monitoring psoriasis patients undergoing systemic treatment. Patients with psoriasis vulgaris and fulfilling inclusion criteria were enrolled in this study, aiming to assess for the first time in the literature whether such inflammatory markers are useful in predicting liver fibrosis. Based on internationally validated FIB-4 index values, patients were divided into two study groups: a low risk of significant fibrosis (LR-SF) and a high risk of significant fibrosis (HR-SF). Patients from HR-SF were significantly older and had higher values of the monocyte-to-lymphocyte ratio (MLR) (p < 0.001), which further significantly correlated with fibrosis severity (p < 0.001). Platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), platelet-to-white blood cell ratio (PWR), and aggregate index of systemic inflammations (AISI) significantly correlated negatively with liver fibrosis (p < 0.001). PWR proved to be the most reliable inflammatory predictor of fibrosis severity (AUC = 0.657). MLR, PWR, and AISI were independent inflammatory markers in multivariate analysis (p < 0.001), while the AST to platelet ratio index (APRI) and AST to ALT ratio (AAR) can be used as additional NITs for significant liver fibrosis (p < 0.001). In limited-resources settings, blood-count-derived inflammatory markers such as MLR, PWR, and AISI, respectively, and hepatic indexes APRI and AAR prove to be of particular help in predicting significant liver fibrosis.
Collapse
Affiliation(s)
- Oana Mirela Tiucă
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Dermatology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Dermatology Clinic, Mures Clinical County Hospital, 540342 Targu Mures, Romania
| | - Silviu Horia Morariu
- Dermatology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Dermatology Clinic, Mures Clinical County Hospital, 540342 Targu Mures, Romania
| | - Claudia Raluca Mariean
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Robert Aurelian Tiucă
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Endocrinology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Endocrinology Department, Mures Clinical County Hospital, 540139 Targu Mures, Romania
| | | | - Ovidiu Simion Cotoi
- Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania
| |
Collapse
|
|
13
|
Cathomas M, Mueller F, Mertineit N, Baumgartner I, Candinas D, Berzigotti A, Maurer MH, Lachenmayer A. Comparison of transarterial bland embolization and drug-eluting beads transarterial chemoembolization for very early and early hepatocellular carcinoma not amenable for surgery or ablation: a single center retrospective data analysis. J Gastrointest Oncol 2023; 14:2167-2177. [PMID: 37969817 PMCID: PMC10643597 DOI: 10.21037/jgo-23-261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 08/14/2023] [Indexed: 11/17/2023] Open
Abstract
Background Transarterial chemoembolization (TACE) is the accepted therapy for intermediate hepatocellular carcinoma (HCC). Although recent data suggests that bland transarterial embolization (TAE) is equally effective in intermediate HCC, not much is known about the efficacy in very early and early HCC not amenable for ablation or resection. We aimed to compare the outcome of patients with very early and early HCC treated by drug-eluting beads TACE (DEB-TACE), a specific technique of TACE using DC beads, and TAE using microparticles with a size of 100 µm up to 700 µm. Methods Clinical data of totally 95 patients with very early and early HCC not amenable for surgery or ablation, treated between 2009 and 2019 at the Department of Visceral Surgery and Medicine and the Interdisciplinary Center of Vascular Interventions, University Hospital Bern, Switzerland, were retrospectively analyzed (52 patients in DEB-TACE and 42 patients in TAE group, respectively). All images were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Primary endpoint was overall survival (OS). Secondary endpoints were local response rate and time to local progression. Results Most patients presented with Child-Pugh A. Thrombocytes were significantly lower in patients treated by TAE. Minor side effects occurred equally in both groups. No differences were detected in terms of OS, local tumor recurrence and response rate. Conclusions Compared with DEB-TACE, TAE is an equally effective and save therapy for very early and early HCC not amenable for resection or ablation without differences in local tumor control and OS.
Collapse
Affiliation(s)
- Marionna Cathomas
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Flavian Mueller
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Nando Mertineit
- Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Radiology, Cantonal Hospital Solothurn, Solothurn, Switzerland
| | - Iris Baumgartner
- Department of Angiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Daniel Candinas
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Martin H. Maurer
- Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Radiology, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Anja Lachenmayer
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| |
Collapse
|
|
14
|
Meroni M, Dongiovanni P. PNPLA3 rs738409 Genetic Variant Inversely Correlates with Platelet Count, Thereby Affecting the Performance of Noninvasive Scores of Hepatic Fibrosis. Int J Mol Sci 2023; 24:15046. [PMID: 37894727 PMCID: PMC10606003 DOI: 10.3390/ijms242015046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/03/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023] Open
Abstract
Noninvasive tests (NITs) including platelets (PLTs) have been proposed to replace hepatic biopsy for the diagnosis of nonalcoholic fatty liver disease (NAFLD), or as more recently redefined, metabolic dysfunction-associated steatotic liver disease (MASLD). There has been reported an inverse correlation between PLTs and progressive MASLD, which is also affected by the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C>G mutation. However, the correlation between low PLTs and PNPLA3 genotype has been poorly investigated. We stratified 1155 biopsy-proven MASLD patients according to PNPLA3 genotype. The hepatic expression of genes involved in megakaryopoiesis was investigated in n = 167 bariatric patients by RNAseq. PLT count progressively decreased according to the number of PNPLA3 at-risk alleles, irrespective of the presence of advanced fibrosis. The hepatic expression of genes involved in PLT biogenesis was associated with the PNPLA3 GG genotype. Finally, the presence of the PNPLA3 homozygosity flattened the accuracy of fibrosis-4 (FIB-4) in discriminating histological fibrosis stages. The PNPLA3 GG genotype may underpower the accuracy of NITs which include PLT count in identifying those patients with potentially reversible stages of fibrosis.
Collapse
Affiliation(s)
| | - Paola Dongiovanni
- Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy;
| |
Collapse
|
|
15
|
Nadinskaia MY, Kodzoeva KB, Gulyaeva KA, Khen MDE, Koroleva DI, Ivashkin VT. Causes for the absence of thrombocytopenia in patients with liver cirrhosis and portal vein thrombosis: A case-control study. ALMANAC OF CLINICAL MEDICINE 2023; 51:207-217. [DOI: 10.18786/2072-0505-2023-51-025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Background: Complications of liver cirrhosis (LC), such as thrombocytopenia and portal vein thrombosis (PVT), have similar pathophysiology. However, the association between PVT and platelet count in LC patients is contradictory.
Aim: To assess factors affecting the platelet count in patients with LC and PVT.
Materials and methods: This was a retrospective case-control study. The cases were 114 patients with LC of various etiologies and newly diagnosed PVT unrelated to invasive hepatocellular carcinoma. From the database of LC patients without PVT, 228 controls were randomly selected with stratification by gender, age and etiology of cirrhosis. The patients from both groups were divided into subgroups with thrombocytopenia ( 150 × 109/L) and without thrombocytopenia (≥ 150 × 109/L). We analyzed the LC etiology, portal hypertension severity (ascites, hepatic encephalopathy, gastroesophageal varices and associated bleedings, the spleen length, and portal vein diameter), laboratory parameters (white blood cell counts, neutrophils, lymphocytes, hemoglobin levels, total protein, albumin, total bilirubin, fibrinogen, neutrophil-to-lymphocyte ratio, and prothrombin); also, the rates of newly diagnosed malignant tumors was assessed. The statistical analysis included calculation of odds ratios (OR) and 95% confidence intervals (CI), logistic regression models with assessment of the model accuracy, and the area under the ROC curve (AUC).
Results: There were no differences in the severity of thrombocytopenia between the case and control groups: thrombocytopenia was severe in 15.8% (18 patients) vs 13.6% (31 patients, p = 0.586); moderate, in 41.2% (47 patients) vs 46.1% (105 patients, p = 0.398) and mild, in 31.6% (36 patients) vs 24.5% (56 patients, p = 0.168). The proportion of the patients without thrombocytopenia was 11.4% (13 patients) in the case group and 15.8% (36 patients) in the control group, with the between-group difference being non-significant (p = 0.276). In the subgroups of patients without thrombocytopenia (both in the cases and in the controls), the proportion alcoholic etiology of LC, white blood cells counts, neutrophils, lymphocytes, and fibrinogen concentrations were significantly higher (p 0.05) than in those with thrombocytopenia. The model based on the outcome "absence of thrombocytopenia" included white blood cells counts, hemoglobin and albumin levels, the presence of newly diagnosed malignant tumors in the case group (model accuracy 90.4%, AUC 0.873), and neutrophil counts and spleen length in the control group (model accuracy 86.4%, AUC 0.855). In the patients with PVT and platelet counts of ≥ 150 × 109/L, the OR for all newly diagnosed malignant tumors was 26.3 (95% CI 7.37–93.97, р 0.0001), for newly diagnosed hepatocellular carcinoma without portal vein invasion 17.42 (95% CI 4.84–62.65, р 0.0001).
Conclusion: In LC patients, the prevalence and severity of thrombocytopenia are not different depending on the PVT presence or absence. The absence of thrombocytopenia in PVT patients is associated with a higher risk of malignant tumors identification, primarily that of hepatocellular carcinoma.
Collapse
|
|
16
|
Mücke MM, Bruns T, Canbay A, Matzdorff A, Tacke F, Tiede A, Trebicka J, Wedemeyer H, Zacharowski K, Zeuzem S, Lange CM. [Use of Thrombopoetin-Receptor-Agonists (TPO-RA) in patients with liver cirrhosis before invasive procedures]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1225-1234. [PMID: 36377140 DOI: 10.1055/a-1934-1867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Advanced chronic liver disease is accompanied with relevant changes in the corpuscular and plasmatic coagulation system. Due to thrombocytopenia that is regularly observed in these patients, platelet transfusions are often performed prior invasive procedures to prevent possible bleeding complications. However, platelet transfusions are associated with clinically significant adverse events and economically relevant health care costs. Thus, avoiding unnecessary platelet transfusions remains pivotal in daily clinical practice. The first step is to carefully check if increasing platelet counts prior to a planned invasive procedure is really necessary. Nowadays, two well-tolerated thrombopoetin-receptor agonists (TPO-RAs), Avatrombopaq and Lusutrombopaq, to treat thrombocytopenia preemptively before an invasive procedure in patients with liver cirrhosis are available. This review provides a guide for clinician when to increase platelet counts prior an invasive procedure in patients with liver cirrhosis and helps to identify situations in which the use of TPO-RA may be reasonable.
Collapse
Affiliation(s)
- Marcus M Mücke
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
| | - Tony Bruns
- Medizinische Klinik III, Uniklinik RWTH Aachen, Rheinisch-Westfaelische Technische Hochschule, Aachen, Germany
| | - Ali Canbay
- Klinik für Innere Medizin, Universitätsklinikum des Knappschaftskrankenhauses Bochum, Bochum, Germany
| | - Axel Matzdorff
- Klinik für Innere Medizin II, Asklepios Klinikum Uckermark GmbH, Schwedt/Oder, Germany
| | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Tiede
- Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule, Hannover, Germany
| | - Jonel Trebicka
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
- Medizinische Klinik B, Universitätsklinikum Münster, Westfälische Wilhelms Universität Münster, Münster, Germany
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Kai Zacharowski
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
| | - Christian M Lange
- Klinik und Poliklinik für Innere Medizin II, LMU Klinikum München, München, Germany
| |
Collapse
|
|
17
|
Sohail R, Hassan IH, Rukh M, Saqib M, Iftikhar M, Mumtaz H. Assessing Thrombocytopenia and Chronic Liver Disease in Southeast Asia: A Multicentric Cross-Sectional Study. Cureus 2023; 15:e43356. [PMID: 37700968 PMCID: PMC10493634 DOI: 10.7759/cureus.43356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2023] [Indexed: 09/14/2023] Open
Abstract
Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease (CLD) across 15 Southeast Asian (India, Pakistan, and Bangladesh) tertiary care centers over a three-month period. The study focused on assessing the fibrosis index (FI) and Model for End-Stage Liver Disease (MELD)-sodium (Na) score's capacity to grade and predict the progression and outcomes of patients with already diagnosed CLD. Methods The cross-sectional study enrolled 377 CLD patients. The study utilized admission registries from 15 tertiary care hospitals in Southeast Asia, spanning from April 2023 to June 2023. Various descriptive variables were collected, including gender, tobacco use (specifically, chewed tobacco), underlying etiology, presence of anemia, leukopenia, pancytopenia, infectious state, and liver cirrhosis diagnosed via traditional ultrasonography. This study examined liver failure indicators, including alanine transaminase levels, compensation status, TCP, and liver transplant (LT) listing. The MELD-Na score was the focus of frequency and percentage analysis. MELD-Na and FI medians and standard deviations were provided. Results The study of 377 patients with CLD found that TCP was present in 4% of patients and leukopenia was present in 12% of patients. The risk of TCP was significantly higher in leukopenic patients (89.5%) than in non-leukopenic patients (52.5%) (p = 0.003). The most common CLD cause was undiagnosable (31%), followed by autoimmune (26%), hepatitis C virus (21%), hepatitis B virus (14%), and schistosomiasis (8%). The majority of patients (98%) had decompensated liver disease. Of the patients, 64% had TCP, while 36% did not. The illness severity indicators MELD score and FI had mean ± SD values of 16.89 ± 6.42 and 4.1 ± 1.06, respectively. Similarly, the prevalence of LT needs among traditional ultrasonography-diagnosed cirrhotic patients was 83.1%, compared to 59.6% among non-cirrhotic patients (p = 0.001). Conclusion Leukopenia and TCP may be linked, which may affect CLD treatment and prognosis in this population. Non-invasive indicators like the FI and MELD-Na score can detect liver fibrosis and severity without invasive procedures, enhancing patient management. These findings highlight the need to improve early diagnosis methods for CLD in Southeast Asia and raise awareness among clinicians about effective diagnostic strategies for non-infectious causes of CLD.
Collapse
Affiliation(s)
- Ramsha Sohail
- Department of Medicine, Jackson Park Hospital, Chicago, USA
| | - Imran H Hassan
- Department of Medicine, Grantham and District Hospital, Grantham, GBR
| | - Mah Rukh
- Department of Medicine, Khyber Teaching Hospital, Peshawar, PAK
| | - Muhammad Saqib
- Department of Medicine, Khyber Teaching Hospital, Peshawar, PAK
| | | | - Hassan Mumtaz
- Department of Urology, Guy's and St. Thomas' Hospital, London, GBR
- General Practice, Surrey Docks Health Centre, London, GBR
- Department of Public Health, Health Services Academy, Islamabad, PAK
- Department of Clinical Research, Maroof International Hospital, Islamabad, PAK
| |
Collapse
|
|
18
|
Lingas EC. Hematological Abnormalities in Cirrhosis: A Narrative Review. Cureus 2023; 15:e39239. [PMID: 37337504 PMCID: PMC10277171 DOI: 10.7759/cureus.39239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 06/21/2023] Open
Abstract
Liver cirrhosis remains a major public health issue. Liver fibrosis leading to cirrhosis is the terminal stage of various chronic liver diseases. Inflammatory cytokines are involved in the pathogenesis. Patients with cirrhosis often have hematological abnormalities, such as anemia and thrombocytopenia, which have multifactorial etiologies. Anemia in cirrhosis could be related to bleeding leading to iron deficiency anemia or other nutritional anemia such as vitamin B12 and folate deficiency. The pathophysiology of thrombocytopenia in liver cirrhosis has been postulated to range from splenic sequestration to bone marrow suppression from toxic agents, such as alcohol. It often complicates management due to the risk of bleeding with severely low platelets. This review aimed to highlight pathogenesis of liver cirrhosis, hematological abnormalities in liver cirrhosis, and their clinical significance.
Collapse
|
|
19
|
Kataria S, Juneja D, Singh O. Approach to thromboelastography-based transfusion in cirrhosis: An alternative perspective on coagulation disorders. World J Gastroenterol 2023; 29:1460-1474. [PMID: 36998429 PMCID: PMC10044856 DOI: 10.3748/wjg.v29.i9.1460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 01/12/2023] [Accepted: 02/27/2023] [Indexed: 03/07/2023] Open
Abstract
Viscoelastic tests, specifically thromboelastography and rotational thromboelastometry, are increasingly being used in the management of postoperative bleeding in surgical intensive care units (ICUs). However, life-threatening bleeds may complicate the clinical course of many patients admitted to medical ICUs, especially those with underlying liver dysfunction. Patients with cirrhosis have multiple coagulation abnormalities that can lead to bleeding or thrombotic complications. Compared to conventional coagulation tests, a comprehensive depiction of the coagulation process and point-of-care availability are advantages favoring these devices, which may aid physicians in making a rapid diagnosis and instituting early interventions. These tests may help predict bleeding and rationalize the use of blood products in these patients.
Collapse
Affiliation(s)
- Sahil Kataria
- Institute of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
| | - Deven Juneja
- Institute of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
| | - Omender Singh
- Institute of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
| |
Collapse
|
|
20
|
Al-Dholae MHH, Salah MK, Al-Ashmali OY, Al Mokdad ASM, Al-Madwami MA. Thrombocytopenia (TCP), MELD Score, and Fibrosis Index (FI) Among Hospitalized Patients with Chronic Liver Disease (CLD) in Ma'abar City, Dhamar Governorate, Yemen: A Cross-Sectional Study. Hepat Med 2023; 15:43-50. [PMID: 37143507 PMCID: PMC10153436 DOI: 10.2147/hmer.s392011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 04/24/2023] [Indexed: 05/06/2023] Open
Abstract
Purpose This study sought to assess the prevalence of thrombocytopenia (TCP), underlying aetiologies of chronic liver disease, and the grading and prognostic systems for chronic liver disease (CLD) using non-invasive biomarkers: the Fibrosis index and the Model for End-Stage Liver Disease-Na (MELD-Na) Score, respectively. Patients and Methods This was a 15-month multi-centric cross-sectional study of 105 patients with chronic liver disease (CLD). The study was conducted using Sept 2019 to Nov 2020 admission records of CLD patients from Ma'abar City in Dhamar Governorate, Yemen. Results A total of 63 (60%) and 42 (40%) patients were identified as thrombocytopenic and non-thrombocytopenic, respectively. The means ± SD of the MELD score and FI were 19 ± 7.302 and 4.1 ± 1.06. TCP prevalence among leukopenic and non-leukopenic patients was 89.5% and 53.5%, respectively (P = 0.004). Likewise, the prevalence of traditional-ultrasonography-diagnosed cirrhotic patients needing liver transplantation (LT) was 82.3% versus 61.3% among corresponding non-cirrhotic patients (P = 0.000). Conclusion The prevalence of TCP among the participants of this study was similar to the global rate. However, the prevalence of decompensation was much higher among CLD patients than that found elsewhere, highlighting a need to improve methods for the early diagnosis of CLD in Yemen. This study also identified problems with the diagnostic work-up for non-infectious aetiologies of CLD. The findings suggest the need to improve clinician awareness about effective diagnostic strategies for these aetiologies.
Collapse
Affiliation(s)
| | - Mohammed Kassim Salah
- Department of Internal Medicine, Faculty of Medicine & Health Sciences, Thamar University, Dhamar, Yemen
| | - Omar Yahya Al-Ashmali
- Department of Pediatrics, Al-Wahda Teaching Hospital, Thamar University, Ma’abar City, Dhamar Governorate, Yemen
- Correspondence: Omar Yahya Al-Ashmali, Department of Paediatrics, Al-Wahda Teaching Hospital, Thamar University, Ma’abar City, Dhamar Governorate, Yemen, Tel +967777638063, Email
| | | | - Mohammed Ali Al-Madwami
- Department of Internal Medicine, Faculty of Medicine & Health Sciences, Thamar University, Dhamar, Yemen
| |
Collapse
|
|
21
|
Lim HI, Cuker A. Thrombocytopenia and liver disease: pathophysiology and periprocedural management. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2022; 2022:296-302. [PMID: 36485111 PMCID: PMC9820432 DOI: 10.1182/hematology.2022000408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Abnormal bleeding in patients with liver disease may result from elevated portal pressure and varix formation, reduced hepatic synthesis of coagulation proteins, qualitative platelet dysfunction, and/or thrombocytopenia. Major mechanisms of thrombocytopenia in liver disease include splenic sequestration and impaired platelet production due to reduced thrombopoietin production. Alcohol and certain viruses may induce marrow suppression. Immune thrombocytopenia (ITP) may co-occur in patients with liver disease, particularly those with autoimmune liver disease or chronic hepatitis C. Drugs used for the treatment of liver disease or its complications, such as interferon, immunosuppressants, and antibiotics, may cause thrombocytopenia. Periprocedural management of thrombocytopenia of liver disease depends on both individual patient characteristics and the bleeding risk of the procedure. Patients with a platelet count higher than or equal to 50 000/µL and those requiring low-risk procedures rarely require platelet-directed therapy. For those with a platelet count below 50 000/µL who require a high-risk procedure, platelet-directed therapy should be considered, especially if the patient has other risk factors for bleeding, such as abnormal bleeding with past hemostatic challenges. We often target a platelet count higher than or equal to 50 000/µL in such patients. If the procedure is elective, we prefer treatment with a thrombopoietin receptor agonist; if it is urgent, we use platelet transfusion. In high-risk patients who have an inadequate response to or are otherwise unable to receive these therapies, other strategies may be considered, such as a trial of empiric ITP therapy, spleen-directed therapy, or transjugular intrahepatic portosystemic shunt placement.
Collapse
Affiliation(s)
- Hana I Lim
- Department of Medicine, Weill Cornell Medicine, New York, NY
| | - Adam Cuker
- Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| |
Collapse
|
|
22
|
Airapetov MI, Eresko SO, Bychkov ER, Lebedev AA, Shabanov PD. Effect of Ethanol on Platelet Biology. BIOCHEMISTRY (MOSCOW), SUPPLEMENT SERIES B: BIOMEDICAL CHEMISTRY 2022. [DOI: 10.1134/s1990750822040023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
23
|
Agbozo WK, Dzudzor B, Nyarko ENY, Lartey-Abrahams K, Mensah RNA, Tachi K. Sociodemographic and medical characteristics of liver cirrhosis deaths in a Ghanaian tertiary hospital. Ghana Med J 2022; 56:259-267. [PMID: 37575631 PMCID: PMC10416286 DOI: 10.4314/gmj.v56i4.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023] Open
Abstract
Objective Cirrhosis is common in Ghana because of its high risk factors prevalence. However, information on cirrhosis in Ghana is lacking. This study aimed to study the clinical, and laboratory characteristics of cirrhotic patients in a tertiary hospital in Ghana. Design This was a retrospective study of sociodemographic characteristics, symptoms and signs, biochemical and fibrotic indices, treatments, and complications data of 247 patients with cirrhosis who died on admission. Setting This study was carried out at the Gastroenterology Unit of the Korle-Bu Teaching Hospital, Ghana. Results Two-thirds (68.0%) of the patients were within 30 to 60 years, with more than half (73.7%) being males. The most common aetiological factors among the patients were Hepatitis B virus infection (53.8%), alcohol use (31.6%) and Hepatitis C virus infection (4.9%). More than half (55.0%) of the patients reported late for admission, and 67.2% died within the first two weeks of admission. The most common clinical feature was abdominal distension (61.1% of patients), and the least was upper-abdominal mass (14.2%). The levels of most liver test parameters were elevated, fibrotic indices were high, and haemoglobin and albumin levels were reduced. More than half (53.8%) of the patients were in Child Pugh class B. The most common complication was hepatic encephalopathy; the least was hepato-renal syndrome. Definite treatment for complications of cirrhosis was lacking. Conclusion Deaths from cirrhosis at the hospital were mostly of young males with chronic hepatitis B infection. Implementation of hepatitis B prevention and treatment guidelines can help reduce cirrhosis deaths. Funding None declared.
Collapse
Affiliation(s)
- William K Agbozo
- Department of Physician Assistantship, School of Medicine, and Health Sciences, Central University, Ghana
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Ghana
| | - Bartholomew Dzudzor
- Department of Medical Biochemistry, University of Ghana Medical School, Ghana
| | - Eric NY Nyarko
- Department of Chemical Pathology, University of Ghana Medical School, Ghana
| | - Karen Lartey-Abrahams
- Department of Physician Assistantship, School of Medicine, and Health Sciences, Central University, Ghana
| | - Roberta N A Mensah
- Department of Physician Assistantship, School of Medicine, and Health Sciences, Central University, Ghana
| | - Kenneth Tachi
- Gastroenterology Unit, Korle-Bu Teaching Hospital, Ghana
- Department of Medicine & Therapeutics, University of Ghana Medical School, Ghana
| |
Collapse
|
|
24
|
Effectiveness and Safety of Avatrombopag in Liver Cancer Patients with Severe Thrombocytopenia: Real-World Data and Challenges. JOURNAL OF ONCOLOGY 2022; 2022:9138195. [PMID: 36405248 PMCID: PMC9668468 DOI: 10.1155/2022/9138195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/28/2022] [Accepted: 10/11/2022] [Indexed: 11/10/2022]
Abstract
Background Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 109/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown. Methods Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled. Avatrombopag dose, peak and absolute platelet count increase, combination treatment with other thrombopoietic agents, responder (peak count ≥50 × 109/L with absolute increase ≥20 × 109/L) rate, and anticancer treatment effect were analyzed. Thrombosis and bleeding events were assessed. Results In total, 93 patients were enrolled, with 72 and 21 in the CLD and non-CLD groups, respectively. Patients with CLD had hepatitis B or C, larger spleen volume, and a higher cirrhosis degree. Baseline platelet counts were similar between two groups (median, 37.0 × 109/L vs. 39.0 × 109/L; P=0.594), while patients without CLD had higher peak platelet (median, 134.0 × 109/L vs. 74.0 × 109/L; P=0.015) and absolute increase (median, 101.0 × 109/L vs. 41.0 × 109/L; P=0.020) after avatrombopag treatment. The responder rate was higher in patients without CLD (100% vs. 76.4%; P=0.010). Combined avatrombopag with other thrombopoietic agents significantly increased platelet count; repeated use of avatrombopag produced similar effects with that of initial treatment. Concerning anticancer treatment effect, patients who responded to avatrombopag had a higher disease control rate. No thrombosis or hemorrhagic events were observed, even in patients with portal vein tumor thrombosis. Conclusion Avatrombopag was safe and effective and ensured successful implementation of anticancer treatment in liver cancer patients with severe thrombocytopenia, accompanied with or without CLD.
Collapse
|
|
25
|
Brigida M, Di Caro S, Petruzziello C, Saviano A, Riccioni ME, Franceschi F, Ojetti V. Vitamin-K Antagonists vs. Direct Oral Anticoagulants on Severity of Upper Gastrointestinal Bleeding: A Retrospective Analysis of Italian and UK Data. J Clin Med 2022; 11:6382. [PMID: 36362611 PMCID: PMC9656833 DOI: 10.3390/jcm11216382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/22/2022] [Accepted: 10/25/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Gastrointestinal bleeding (GIB) is one of most frequent and significant challenges for emergency physicians and gastroenterologists. Mortality for upper (U) GIB is high, especially in the elderly and comorbid patients. However, there is scant evidence in the literature concerning an assessment of warfarin (VKA) and direct oral anticoagulants (DOACs) in terms of upper gastrointestinal bleeding (UGIB) severity. Aims: Using data from two different settings (Italy and the UK), we aimed to compare the impact of VKA and DOACs on the severity of UGIB. Methods: Retrospective bicentric study on adult patients under VKA or DOACs admitted either to the emergency department at the Gemelli Hospital in Rome, Italy or University College Hospital in London, UK, with suspected UGIB from 01/01/2017 to 31/12/2018. Univariate analysis with Fisher’s exact test, and analysis of variance (ANOVA) were used. Results: 106 patients (62 M/44 F; mean age 71.2 ± 16.9 yrs) were enrolled and divided into the VKA group (N = 57; M: 56%, mean age: 64.9 ± 21.3 yrs) and the DOAC group (N = 49; M: 61%; mean age: 77.6 ± 12.5 yrs). At univariate analysis, the VKA group presented two endoscopic diagnoses more frequently than the DOAC group (26% vs. 8%, p < 0.05), were more frequently endoscopically treated (44% vs. 22%, p < 0.05), rescoped (12% vs. 2%, p = 0.048) and hospitalized (79% vs. 53%, p = 0.01) with a longer length of stay, LOS (VKA: 58% > 5 days vs. DOAC: 68% < 5 days, p = 0.01). There was no difference in terms of hemoglobin level on admission, however the requirement of blood transfusions was higher in the VKA group (60% vs. 41%, p = 0.041). One third of the VKA group showed a lower platelet count than the DOAC group (33% vs. 8%, p = 0.01). No statistically significant differences for in-hospital mortality were observed. For the ANOVA, the type of anticoagulant used was the only significant predictor of need to rescope (p = 0.041) and a significant co-predictor for a LOS > 5 days (p = 0.009; as well as cirrhosis, p = 0.013 and age, p = 0.005). Conclusions: Our outcomes revealed a more severe UGIB in patients on VKA, but the impact of comorbidities (i.e., more cirrhotic patients in the VKA group) cannot be disregarded. DOAC subgroup descriptive analysis, even though on a little cohort, showed higher bleeding severity for rivaroxaban.
Collapse
Affiliation(s)
| | - Simona Di Caro
- University College London Hospital (UCLH) NHS Foundation Trust, London NW1 2BU, UK
- University College London, London NW1 2BU, UK
| | | | | | - Maria Elena Riccioni
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Franceschi
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Veronica Ojetti
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| |
Collapse
|
|
26
|
Wang YS, Wang W, Zhang S, Zhang SY, Shen AZ, Wang W, Song HC, Yao HZ, Song RP, Meng FZ, Li L, Nashan B, Wang JZ, Liu LX. Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study. Front Pharmacol 2022; 13:1009612. [PMID: 36267268 PMCID: PMC9577549 DOI: 10.3389/fphar.2022.1009612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/13/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD).Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias.Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ2 = 1.659, p = 0.198; Waldχ2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ2 = 0.540, p = 0.910; Waldχ2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05).Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.
Collapse
Affiliation(s)
- Yong-Shuai Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Wei Wang
- Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Sai Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Shen-Yu Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Ai-Zong Shen
- Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Wei Wang
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Hua-Chuan Song
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Huan-Zhang Yao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Rui-Peng Song
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Fan-Zheng Meng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Lei Li
- Department of Infectious Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Bjoern Nashan
- Department of Organ transplant center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Ji-Zhou Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui, China
- *Correspondence: Ji-Zhou Wang, ; Lian-Xin Liu,
| | - Lian-Xin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui, China
- *Correspondence: Ji-Zhou Wang, ; Lian-Xin Liu,
| |
Collapse
|
|
27
|
Orme ME, Bentley R, Marcella S, Peck-Radosavljevic M, Perard R, Wedemeyer H, Yoshiji H, Agarwal K, Dusheiko G. Systematic Review with Meta-Analysis: Efficacy and Safety of Lusutrombopag for Severe Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Invasive Procedures. Adv Ther 2022; 39:4169-4188. [PMID: 35836089 PMCID: PMC9402754 DOI: 10.1007/s12325-022-02235-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/17/2022] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Lusutrombopag is an oral thrombopoietin receptor agonist (TPO-RA). Clinical trials have shown lusutrombopag's efficacy in reducing need for preoperative platelet transfusion in patients with chronic liver disease (CLD) and severe thrombocytopenia. This analysis assessed efficacy and safety of lusutrombopag in patients with severe thrombocytopenia and CLD undergoing planned invasive procedures. METHODS An electronic database search (through 1 December 2020) identified three randomised, placebo-controlled, double-blind clinical trials comparing lusutrombopag with placebo in patients with CLD and platelet count below 50 × 109/L scheduled to undergo a procedure with a perioperative bleeding risk. A random-effects meta-analysis examined treatment effect, with Cochrane Collaboration's tool assessing risk of bias. RESULTS The meta-analysis included 343 (lusutrombopag 3 mg, n = 173; placebo, n = 170) patients. More patients met the criteria for treatment response (platelet count at least 50 × 109/L and increase of at least 20 × 109/L from baseline anytime during the study) with lusutrombopag versus placebo (risk ratio [RR] 6.39; 95% confidence interval [CI] 3.69, 11.07; p < 0.0001). The primary efficacy outcome, proportion of patients requiring no platelet transfusion and no rescue therapy for bleeding for at least 7 days post procedure, was achieved by more patients treated with lusutrombopag versus placebo (RR 3.42; 95% CI 1.86, 6.26; p = 0.0001). The risk of any bleeding event was significantly lower with lusutrombopag compared to placebo (RR 0.55; 95% CI 0.32, 0.95; p = 0.03); conversely, thrombosis event rates were similar between lusutrombopag and placebo (RR 0.79; 95% CI 0.19, 3.24; p = 0.74). CONCLUSION This meta-analysis showed that treatment of severe thrombocytopenia with lusutrombopag in patients with CLD prior to a planned invasive procedure was efficacious and safe in increasing platelet counts, avoiding the need for platelet transfusions, and reducing risk of bleeding, thereby enhancing the certainty of evidence supporting the efficacy and safety of lusutrombopag.
Collapse
Affiliation(s)
- Michelle E Orme
- ICERA Consulting Ltd., 17 Redbridge Close, Swindon, Wiltshire, UK.
| | | | | | - Markus Peck-Radosavljevic
- Abteilung Innere Medizin und Gastroenterologie (IMuG), mit Zentrale Aufnahme und Erstversorgung (ZAE), Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara Prefecture, Japan
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Geoffrey Dusheiko
- University College London Medical School and King's College Hospital, London, UK
| |
Collapse
|
|
28
|
Birnbaum JA, Herman HS, Gao Q, Koenigsberg M, Sigal SH. The Prognostic Significance of the Platelet Count in Alcoholic Hepatitis. GASTRO HEP ADVANCES 2022; 2:8-15. [PMID: 39130158 PMCID: PMC11308416 DOI: 10.1016/j.gastha.2022.07.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 07/29/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Thrombocytopenia is present in up to 76% of patients with chronic liver disease, and lower platelet counts (PCs) are associated with greater severity of portal hypertension. In this study, we assess the relationship of PC in patients with a clinical diagnosis of severe alcoholic hepatitis (SAH) with clinical severity and response to corticosteroid (CS) therapy. Methods Clinical characteristics, treatment, and hospital outcomes for patients admitted with SAH were analyzed from an electronic health record system. Patients were categorized based on admission PC (k/uL) into 5 categories: <50, 50-99, 100-149, 150-199, and ≥200. Frequency of complications (acute kidney injury, ascites, and hepatic encephalopathy), length of stay, and admission to an intensive care unit were analyzed across PC categories. Characteristics of patients who did and did not receive at least 4 days of CS therapy were compared. Results Among 159 patients, 15 (9.4%) were in the PC < 50 category, 42 (26.4%) in PC 50-99, 51 (32%) in PC 100-149, 23 (14.5%) in PC 150-199, and 28 (17.6%) in PC ≥ 200. A higher admission PC was associated with greater white blood cell count, absolute neutrophil count, and total bilirubin (P < .05). Patients with higher PC on admission were more likely to receive steroids. PC was inversely associated with Lille score at treatment day 4 (P < .05). Conclusion A higher PC in SAH was associated with a greater inflammatory response and total bilirubin. Patients with a higher PC were more likely to receive CS and have a favorable treatment response.
Collapse
Affiliation(s)
| | | | - Qi Gao
- Albert Einstein College of Medicine, Bronx, New York
| | - Mordecai Koenigsberg
- Albert Einstein College of Medicine, Bronx, New York
- Department of Radiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
| | - Samuel H. Sigal
- Albert Einstein College of Medicine, Bronx, New York
- Division of Hepatology, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
| |
Collapse
|
|
29
|
Gallo P, Terracciani F, Di Pasquale G, Esposito M, Picardi A, Vespasiani-Gentilucci U. Thrombocytopenia in chronic liver disease: Physiopathology and new therapeutic strategies before invasive procedures. World J Gastroenterol 2022; 28:4061-4074. [PMID: 36157107 PMCID: PMC9403422 DOI: 10.3748/wjg.v28.i30.4061] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/21/2022] [Accepted: 07/18/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment. Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin (TPO) in its physiopathology. Severe thrombocytopenia (platelet count < 50000/μL) complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures, which may be therefore delayed or canceled even if lifesaving. In the very last years, the development of new drugs which exceed the limits of the current standard of care (platelet transfusions, either immediately before or during the procedure) paves the way to a new scenario in the management of this population of patients. Novel agents, such as the TPO-receptor agonists avatrombopag and lusutrombopag, have been developed in order to increase platelet production as an alternative to platelet transfusions. These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion, without any delay in scheduled interventions. Altogether, it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.
Collapse
Affiliation(s)
- Paolo Gallo
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Francesca Terracciani
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Giulia Di Pasquale
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Matteo Esposito
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Antonio Picardi
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | | |
Collapse
|
|
30
|
Kulkarni AV, Rabiee A, Mohanty A. Management of Portal Hypertension. J Clin Exp Hepatol 2022; 12:1184-1199. [PMID: 35814519 PMCID: PMC9257868 DOI: 10.1016/j.jceh.2022.03.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Portal hypertension is the cause of the clinical complications associated with cirrhosis. The primary complications of portal hypertension are ascites, acute variceal bleed, and hepatic encephalopathy. Hepatic venous pressure gradient measurement remains the gold standard test for diagnosing cirrhosis-related portal hypertension. Hepatic venous pressure gradient more than 10 mmHg is associated with an increased risk of complications and is termed clinically significant portal hypertension (CSPH). Clinical, laboratory, and imaging methods can also aid in diagnosing CSPH non-invasively. Recently, deep learning methods have been demonstrated to diagnose CSPH effectively. The management of portal hypertension is always individualized and is dependent on the etiology, the availability of therapies, and the degree of portal hypertension complications. In this review, we discuss the diagnosis and management of cirrhosis-related portal hypertension in detail. Also, we highlight the history of portal hypertension and future research areas in portal hypertension.
Collapse
Key Words
- ACLF, acute-on-chronic liver failure
- AKI, acute kidney injury
- APRI, AST to platelet ratio
- AST, aspartate transaminase
- BB, Beta blocker
- BRTO, balloon occluded retrograde transvenous obliteration
- CKD, chronic kidney disease
- CSPH, clinically significant portal hypertension
- CT, computed tomography
- GFR, glomerular filtration rate
- GOV, gastrpoesopahegal varices
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- ICG, indocyanine green
- LOLA, l-ornithine l-aspartate
- NAFLD, Non-alcoholic fatty liver disease
- SBP, spontaneous bacterial peritonitis
- SGLT2I, sodium glucose co-transporter 2 inhibitors
- SSM, splenic stiffness measurement
- TE, transient elastography
- TIPS, transjugular intrahepatic portosystemic shunt
- VITRO, von Willebrand factor to platelet counts
- acute kidney injury
- ascites
- hemodynamics
- history
- vasoconstrictors
Collapse
Affiliation(s)
| | | | - Arpan Mohanty
- Boston University School of Medicine, Boston, MA, USA
| |
Collapse
|
|
31
|
Lu J, Jamieson BD, Hui AM. Avatrombopag ethnic sensitivity analysis in chronic liver disease and thrombocytopenia patients: individual-level pooled analysis. Therap Adv Gastroenterol 2022; 15:17562848221105976. [PMID: 35795378 PMCID: PMC9252017 DOI: 10.1177/17562848221105976] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/19/2022] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Few data have been published on the ethnic sensitivity of effectiveness, pharmacokinetics (PK), and pharmacodynamics (PD) of avatrombopag for the management of thrombocytopenia in patients with chronic liver disease (CLD). METHODS An ethnic sensitivity analysis was performed based on the results from two phase III studies (ADAPT-1 and ADAPT-2), with a primary endpoint of the proportion of patients without the requirement of platelet transfusion or rescue treatment for bleeding after randomization to 7 days following a scheduled procedure, and three phase I studies in healthy subjects. Cochran-Mantel-Haenszel and Fisher's exact tests were used to compare the differences in effectiveness in different ethnicities and overall population. RESULTS In total, 435 patients (placebo, n = 158; avatrombopag, n = 277) were stratified into various ethnic groups: 121 East Asians, including the subgroup of 27 Chinese, and 259 Caucasians. The proportion of patients who did not receive a platelet transfusion and those with a platelet count ⩾50 × 109/L in the avatrombopag 40 and 60 mg groups were higher than that of placebo for all ethnicities and in the overall population. Statistical significance was obtained in the overall population and for all ethnicities other than Chinese patients, a group with a very small sample size. No significant difference was observed in the proportion of responders in each ethnic group compared to overall population (p > 0.05). The incidence of adverse events in East Asians was similar to that in both Caucasians and the overall population. CONCLUSION Avatrombopag was effective and safe in the management of thrombocytopenia in Chinese patients with CLD. Ethnicity does not appear to influence the efficacy, safety, PK, or PD of avatrombopag.
Collapse
Affiliation(s)
- Jun Lu
- Clinical Research Department, Shanghai Fosun Pharmaceutical Development, Co., Ltd, Shanghai, China
| | | | | |
Collapse
|
|
32
|
Rock JR, Kos CA, Lemaire A, Ikegami H, Russo MJ, Moin D, Dulnuan K, Iyer D. Single center first year experience and outcomes with Impella 5.5 left ventricular assist device. J Cardiothorac Surg 2022; 17:124. [PMID: 35606780 PMCID: PMC9128113 DOI: 10.1186/s13019-022-01871-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 04/30/2022] [Indexed: 11/10/2022] Open
Abstract
Background The Impella 5.5® was approved by the FDA for use for mechanical circulatory support up to 14 days in late 2019 at limited centers in the United States. Our single center’s experience with Impella 5.5® can expand the overall understanding for achieving successful patient outcomes as well as provide support for the expansion of its FDA-approved use. Methods This study is an IRB-approved single-center retrospective cohort analysis of hospitalized adult patient characteristics and outcomes in cases where the Impella 5.5® was utilized for mechanical circulatory support. Results A total of 26 implanted Impella 5.5® devices were identified in 24 hospitalized patients at our institution from January 2020 to January 2021. The overall survival rate during index hospitalization was 75%. Eleven Impella 5.5® devices were identified in 10 patients with an average device implantation greater than 14 days. Average device implantation for this subgroup was 27 days with a range of 15–80 days. Survival rate for Impella 5.5® use greater than 14 days was 67%. In the entire cohort and subgroup of device implantation > 14 days, evidence of end organ damage improved with Impella 5.5® use. Complications in our cohort and subgroup of device implantation > 14 days were similar to previously reported complication incidence of axillary inserted LVAD devices. Conclusions Our institution’s experience with the Impella 5.5® has been strongly positive with favorable outcomes and helps to establish the Impella 5.5® as a viable option for mechanical circulatory support beyond 14 days. Supplementary Information The online version contains supplementary material available at 10.1186/s13019-022-01871-1.
Collapse
Affiliation(s)
- Joanna R Rock
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. .,, New Brunswick, USA.
| | - Cynthia A Kos
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Anthony Lemaire
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Robert Wood Johnson University Hospital, RWJBarnabas Health, New Brunswick, NJ, USA
| | - Hirohisa Ikegami
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Robert Wood Johnson University Hospital, RWJBarnabas Health, New Brunswick, NJ, USA
| | - Mark J Russo
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Robert Wood Johnson University Hospital, RWJBarnabas Health, New Brunswick, NJ, USA
| | - Danyaal Moin
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Robert Wood Johnson University Hospital, RWJBarnabas Health, New Brunswick, NJ, USA
| | - Kenneth Dulnuan
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Robert Wood Johnson University Hospital, RWJBarnabas Health, New Brunswick, NJ, USA
| | - Deepa Iyer
- Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Robert Wood Johnson University Hospital, RWJBarnabas Health, New Brunswick, NJ, USA
| |
Collapse
|
|
33
|
Kim JH, Kim SE, Song DS, Kim HY, Yoon EL, Kim TH, Jung YK, Suk KT, Jun BG, Yim HJ, Kwon JH, Lee SW, Kang SH, Kim MY, Jeong SW, Jang JY, Yoo JJ, Kim SG, Jin YJ, Cheon GJ, Kim BS, Seo YS, Kim HS, Sinn DH, Chung WJ, Kim HY, Lee HA, Nam SW, Kim IH, Suh JI, Kim JH, Chae HB, Sohn JH, Cho JY, Kim YJ, Yang JM, Park JG, Kim W, Cho HC, Kim DJ. Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration. J Clin Med 2022; 11:2463. [PMID: 35566588 PMCID: PMC9103428 DOI: 10.3390/jcm11092463] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/23/2022] [Accepted: 04/24/2022] [Indexed: 02/05/2023] Open
Abstract
Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.
Collapse
Affiliation(s)
- Jung-Hee Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea; (J.-H.K.); (K.-T.S.); (H.-S.K.); (D.-J.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Korea
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea; (J.-H.K.); (K.-T.S.); (H.-S.K.); (D.-J.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Korea
| | - Do-Seon Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (D.-S.S.); (H.-Y.K.); (J.-H.K.); (S.-W.L.); (J.-M.Y.)
| | - Hee-Yeon Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (D.-S.S.); (H.-Y.K.); (J.-H.K.); (S.-W.L.); (J.-M.Y.)
| | - Eileen L. Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Korea; (E.L.Y.); (J.-H.S.)
| | - Tae-Hyung Kim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Korea; (T.-H.K.); (Y.-K.J.); (H.-J.Y.); (Y.-S.S.); (J.-H.K.)
| | - Young-Kul Jung
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Korea; (T.-H.K.); (Y.-K.J.); (H.-J.Y.); (Y.-S.S.); (J.-H.K.)
| | - Ki-Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea; (J.-H.K.); (K.-T.S.); (H.-S.K.); (D.-J.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Korea
| | - Baek-Gyu Jun
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Korea; (B.-G.J.); (S.-H.K.)
| | - Hyung-Joon Yim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Korea; (T.-H.K.); (Y.-K.J.); (H.-J.Y.); (Y.-S.S.); (J.-H.K.)
| | - Jung-Hyun Kwon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (D.-S.S.); (H.-Y.K.); (J.-H.K.); (S.-W.L.); (J.-M.Y.)
| | - Sung-Won Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (D.-S.S.); (H.-Y.K.); (J.-H.K.); (S.-W.L.); (J.-M.Y.)
| | - Seong-Hee Kang
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Korea; (B.-G.J.); (S.-H.K.)
| | - Moon-Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea;
| | - Soung-Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (S.-W.J.); (J.-Y.J.)
| | - Jae-Young Jang
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (S.-W.J.); (J.-Y.J.)
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Korea; (J.-J.Y.); (S.-G.K.)
| | - Sang-Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Korea; (J.-J.Y.); (S.-G.K.)
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22212, Korea;
| | - Gab-Jin Cheon
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 25440, Korea;
| | - Byung-Seok Kim
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu 42472, Korea;
| | - Yeon-Seok Seo
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Korea; (T.-H.K.); (Y.-K.J.); (H.-J.Y.); (Y.-S.S.); (J.-H.K.)
| | - Hyung-Su Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea; (J.-H.K.); (K.-T.S.); (H.-S.K.); (D.-J.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Korea
| | - Dong-Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06531, Korea;
| | - Woo-Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Korea;
| | - Hwi-Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea; (H.-Y.K.); (H.-A.L.)
| | - Han-Ah Lee
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea; (H.-Y.K.); (H.-A.L.)
| | - Seung-Woo Nam
- Department of Internal Medicine, National Medical Center, Seoul 04564, Korea;
| | - In-Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju 54896, Korea;
| | - Jung-Il Suh
- Department of Gastroenterology, Dongguk University College of Medicine, Kyongju 38067, Korea;
| | - Ji-Hoon Kim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Korea; (T.-H.K.); (Y.-K.J.); (H.-J.Y.); (Y.-S.S.); (J.-H.K.)
| | - Hee-Bok Chae
- Department of Internal Medicine, Medical Research Institute, Chungbuk National University College of Medicine, Cheongju 28644, Korea;
| | - Joo-Hyun Sohn
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Korea; (E.L.Y.); (J.-H.S.)
| | - Ju-Yeon Cho
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 61452, Korea;
| | - Yoon-Jun Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Jin-Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (D.-S.S.); (H.-Y.K.); (J.-H.K.); (S.-W.L.); (J.-M.Y.)
| | - Jung-Gil Park
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu 42415, Korea;
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Korea;
| | - Hyun-Chin Cho
- Department of Internal Medicine, Gyeongsang National University Hospital, Jinju 52727, Korea;
| | - Dong-Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea; (J.-H.K.); (K.-T.S.); (H.-S.K.); (D.-J.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Korea
| |
Collapse
|
|
34
|
Baihaqi FA, Delarosa DO. Correlation between Platelet Count and Grading of Esophageal Varices in Liver Cirrhosis Patients: A Meta-Analysis. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Esophageal varices are a major complication of liver cirrhosis. Esophageal varices bleeding is life-threatening and an urgent medical emergency. Low platelet count and esophageal varices are common findings in liver cirrhosis. Platelet count is suggested as a non-invasive screening tool to predict the grading of esophageal varices in liver cirrhosis patients. Several studies have found a correlation between platelet count and grading of esophageal varices in liver cirrhosis patients. However, the results are conflicting.
AIM: This meta-analysis aimed to evaluate the correlation between platelet count and the grading of esophageal varices in liver cirrhosis patients.
METHODS: A systematic literature search was performed through the database search from PubMed, SCOPUS, Ovid EMBASE, and EuropePMC to obtain all relevant articles with the following search terms: "correlation" and "platelet" or "thrombocytopenia" AND "esophageal varices" and "liver cirrhosis" or "chronic liver disease" that were published within the year of 2000-2021. Articles were collected by using PRISMA flow diagrams. The data were extracted from the eligible study within inclusion and exclusion criteria. The quality of each study was assessed using the Newcastle Ottawa Scale (NOS). A meta-analysis was conducted to determine the overall pooled correlation coefficient (r) and 95% confidence interval (CI).
RESULTS: There were a total of 1008 patients from eight included studies. The meta-analysis showed that the pooled correlation coefficient between platelet count and grading of esophageal varices in liver cirrhosis patients was r = -0.42 (95%CI -0.65 to -0.13; p = 0.005; I2 = 96.06%).
CONCLUSION: There was a moderate negative correlation between platelet count and grading of esophageal varices. Thus, low platelet count may indicate higher grades of esophageal varices in liver cirrhosis patients.
Collapse
|
|
35
|
Airapetov MI, Eresko SO, Bychkov ER, Lebedev AA, Shabanov PD. [Effect of ethanol on platelet biology]. BIOMEDITSINSKAIA KHIMIIA 2022; 68:81-92. [PMID: 35485482 DOI: 10.18097/pbmc20226802081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
In recent years, interest in the study of platelets, significantly increased due to recent discoveries providing convincing evidence that their functions by are not limited to their participation in the blood coagulation mechanism. Many works are devoted to the study of the functional state of platelets under conditions of acute and chronic alcohol exposure. The results of such studies can be useful for the development of new markers of the degree of alcohol intoxication of the body for the subsequent choice of the method drug correction of disorders caused by acute or chronic alcohol effects. The review summarizes results in vivo and in vitro of studies performed during more than 60 years on the effect of ethanol on the biogenesis, number, morphology and biochemistry of platelets.
Collapse
Affiliation(s)
- M I Airapetov
- Department of Neuropharmacology, Institute of Experimental Medicine, Saint Petersburg, Russia; Department of Pharmacology, St. Petersburg State Pediatric Medical University, Saint Petersburg, Russia
| | - S O Eresko
- Department of Neuropharmacology, Institute of Experimental Medicine, Saint Petersburg, Russia; Research and Training Center of Molecular and Cellular Technologies, Saint Petersburg, Russia
| | - E R Bychkov
- Department of Neuropharmacology, Institute of Experimental Medicine, Saint Petersburg, Russia
| | - A A Lebedev
- Department of Neuropharmacology, Institute of Experimental Medicine, Saint Petersburg, Russia
| | - P D Shabanov
- Department of Neuropharmacology, Institute of Experimental Medicine, Saint Petersburg, Russia; Department of Pharmacology, Kirov Military Medical Academy, Saint Petersburg, Russia
| |
Collapse
|
|
36
|
Samir D, Nour H, Maroua C. Assessment of Haematological Complications and Prognostic Value of Oxidative Stress Markers in Viral Hepatitis B Patients. JOURNAL OF MEDICAL SCIENCES 2022. [DOI: 10.3923/jms.2022.44.52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
|
|
37
|
Keshvari S, Genz B, Teakle N, Caruso M, Cestari MF, Patkar OL, Tse BWC, Sokolowski KA, Ebersbach H, Jascur J, MacDonald KPA, Miller G, Ramm GA, Pettit AR, Clouston AD, Powell EE, Hume DA, Irvine KM. Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease. Dis Model Mech 2022; 15:274391. [PMID: 35169835 PMCID: PMC9044210 DOI: 10.1242/dmm.049387] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 02/08/2022] [Indexed: 11/20/2022] Open
Abstract
Resident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, utilizing a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodeling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.
Collapse
Affiliation(s)
- Sahar Keshvari
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Berit Genz
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.,QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Ngari Teakle
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Melanie Caruso
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Michelle F Cestari
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Omkar L Patkar
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Brian W C Tse
- Preclinical Imaging Facility, Translational Research Institute, Brisbane, Queensland, Australia
| | - Kamil A Sokolowski
- Preclinical Imaging Facility, Translational Research Institute, Brisbane, Queensland, Australia
| | - Hilmar Ebersbach
- Novartis Institutes for Biomedical Research (NIBR), Fabrikstrasse 2, Novartis Campus, CH-4056 Basel, Switzerland
| | - Julia Jascur
- Novartis Institutes for Biomedical Research (NIBR), Fabrikstrasse 2, Novartis Campus, CH-4056 Basel, Switzerland
| | | | | | - Grant A Ramm
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Allison R Pettit
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Andrew D Clouston
- Envoi Specialist Pathologists, Brisbane, Qld, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Elizabeth E Powell
- Faculty of Medicine, The University of Queensland, Brisbane, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - David A Hume
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Katharine M Irvine
- Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| |
Collapse
|
|
38
|
Yoshida M, Tateishi R, Hiroi S, Fujiwara M, Kitanishi Y, Iwasaki K, Takeshima T, Igarashi A. Changes in Platelet Counts and Thrombocytopenia Risk in Patients with Chronic Liver Disease with Different Etiologies Using Real-World Japanese Data. Adv Ther 2022; 39:992-1003. [PMID: 34928469 PMCID: PMC8866341 DOI: 10.1007/s12325-021-02008-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/29/2021] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Thrombocytopenia, a common complication of chronic liver disease (CLD), adversely affects the treatment in patients requiring invasive procedures. Multiple pathophysiological mechanisms contribute to the development of thrombocytopenia; thus, its incidence could differ among CLD etiologies. We investigated the risk of decline in platelet counts and developing thrombocytopenia across different CLDs in a real-world Japanese setting. METHODS A Japanese claims database including 25 million patients (April 2008-August 2018) was used. Patients with at least one CLD diagnosis were classified into nine mutually exclusive categories: hepatitis B, hepatitis C, hepatitis B and C, unspecified viral hepatitis, autoimmune hepatitis, toxin/drug-induced hepatitis, alcoholic hepatitis, nonalcoholic steatohepatitis, and others. A random effects model was used to estimate the changes in platelet counts; proportional hazard analyses were used to examine factors associated with the incidence of thrombocytopenia based on the diagnosis. Patients with laboratory test data as variables were included in each analysis. RESULTS The simulation included 68,536 patients. The mean values representing changes in the platelet count were significantly negative in the hepatitis C patients and negative, though non-significant, in the hepatitis B, toxin/drug-induced hepatitis, alcoholic hepatitis, and nonalcoholic steatohepatitis patients. In the proportional hazard analysis, 708 of 22,728 patients had thrombocytopenia. The hazard ratio (HR) was significantly high for patients with hepatitis B (HR, 2.879; p < 0.001), hepatitis C (HR, 1.876; p < 0.001), and hepatitis B and C (HR, 2.992; p < 0.001). CONCLUSION A decreasing tendency in platelet counts was observed in most CLD etiologies, with hepatitis C showing a significant decrease. The incidence of thrombocytopenia was mostly associated with hepatitis B and/or C. Further research is warranted to elucidate the discrepancy between the decline in platelet counts and thrombocytopenia diagnosis, considering the factors relevant to the diagnosis, such as the frequency of outpatient visits and CLD treatment.
Collapse
Affiliation(s)
- Manami Yoshida
- Medical Affairs, Shionogi & Co., Ltd., 7F, Tekko Building, 1-8-2, Marunouchi, Chiyoda-ku, Tokyo, 100-0005, Japan.
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
| | - Ryosuke Tateishi
- Department of Gastroenterology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Shinzo Hiroi
- Medical Affairs, Shionogi & Co., Ltd., 7F, Tekko Building, 1-8-2, Marunouchi, Chiyoda-ku, Tokyo, 100-0005, Japan
| | - Masakazu Fujiwara
- Data Science Department, Shionogi & Co., Ltd., 3-1-8, Doshomachi, Chuo-ku, Osaka, 541-0045, Japan
| | - Yoshitake Kitanishi
- Data Science Department, Shionogi & Co., Ltd., 3-1-8, Doshomachi, Chuo-ku, Osaka, 541-0045, Japan
| | - Kosuke Iwasaki
- Milliman, Inc., 8F, Kojimachi 1-chome Building, 1-6-2 Kojimachi, Chiyoda-ku, Tokyo, 102-0083, Japan
| | - Tomomi Takeshima
- Milliman, Inc., 8F, Kojimachi 1-chome Building, 1-6-2 Kojimachi, Chiyoda-ku, Tokyo, 102-0083, Japan
| | - Ataru Igarashi
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
- Unit of Public Health and Preventive Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| |
Collapse
|
|
39
|
Lindquist I, Olson SR, Li A, Al-Samkari H, Jou JH, McCarty OJT, Shatzel JJ. The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis. Platelets 2022; 33:66-72. [PMID: 33459573 PMCID: PMC8286270 DOI: 10.1080/09537104.2020.1859102] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/05/2020] [Accepted: 10/07/2020] [Indexed: 01/04/2023]
Abstract
Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 109/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6-6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3-0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5-0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6-2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.
Collapse
Affiliation(s)
- Ingrid Lindquist
- Division of General Internal Medicine and Geriatrics, Oregon Health & Science University, Portland, OR, USA
| | - Sven R Olson
- Division of Hematology and Oncology, Oregon Health & Science University, Portland, OR, USA
| | - Ang Li
- Section of Hematology Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Hanny Al-Samkari
- Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Janice H Jou
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, OR, USA
| | - Owen J T McCarty
- Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
| | - Joseph J Shatzel
- Division of Hematology and Oncology, Oregon Health & Science University, Portland, OR, USA
- Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
| |
Collapse
|
|
40
|
Xu X, Li C, Chen J, Liu X, Su H, Tong J, Hu J. Relationship Between Platelet to White Blood Cell Ratio and 30-Day Prognosis of Patients with Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2021; 21. [DOI: 10.5812/hepatmon.118640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
Background: Acute-on-chronic liver failure (ACLF) is always associated with thrombocytopenia or leukocytosis. Therefor the platelet to white blood cell ratio (PWR) in ACLF patients is always reduced. Objectives: Here, we assessed the relationship between PWR and prognosis in ACLF patients. Methods: A retrospective cohort of 415 patients, including 100 patients that were diagnosed of chronic hepatitis B, 104 patients suffered of HBV-related liver cirrhosis and 211 patients suffered of HBV-related ACLF, was investigated. Univariate and multivariate COX models were used to investigate the relationship between PWR and 30-day survival in patients with ACLF. Factors affecting PWR in ACLF patients were also analysed using logistic regression analysis. Results: At baseline, the platelet count in patients with HBV-related ACLF was significantly lower than that in patients with CHB and patients suffered of HBV-related cirrhosis. The PWR value was much higher in the survivors of ACLF than in ACLF patients who died. PWR, age, total bilirubine, prothrombin activity, and aspartate transaminase were independent predictors of the 30-day survival rate of ACLF patients. We also found that ascites and infection were independent factors related to the decrease of PWR in ACLF patients. Conclusions: The PWR value was significant declined in ACLF patients. And it was independent risk factors for the survival rate of those patients.
Collapse
|
|
41
|
Flisiak R, Antonov K, Drastich P, Jarcuska P, Maevskaya M, Makara M, Puljiz Ž, Štabuc B, Trifan A. Practice Guidelines of the Central European Hepatologic Collaboration (CEHC) on the Use of Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease Undergoing Invasive Procedures. J Clin Med 2021; 10:5419. [PMID: 34830701 PMCID: PMC8625449 DOI: 10.3390/jcm10225419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/01/2021] [Accepted: 11/17/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Second-generation thrombopoietin receptor agonists (TPO-RAs) are emerging as the new standard for managing thrombocytopenia (TCP) in patients with chronic liver diseases (CLDs) undergoing scheduled procedures. However, practical guidance for their routine use in CLD patients undergoing specific invasive procedures is lacking. METHODS These practice guidelines were developed by the Initiative Group for Central European Hepatologic Collaboration (CEHC), composed of nine hepatologist/gastroenterologist experts from Central Europe. Using an adapted Delphi process, the CEHC group selected ten invasive procedures most relevant to the hepatology/gastroenterology setting in the region. Consensus recommendations for each invasive procedure are reported as a final percentage of expert panel responses. RESULTS A consensus was agreed that TPO-RAs should be considered for raising platelet count in CLD patients undergoing scheduled abdominal surgery, high-bleeding risk dentistry, endoscopic polypectomy, endoscopic variceal ligation, liver biopsy, liver surgery, liver transplantation and percutaneous ablation, but it was also agreed that they are less beneficial or not necessary for endoscopy without intervention and paracentesis. CONCLUSIONS Using a modified Delphi method, experts reached an agreement for TCP management in CLD patients undergoing ten invasive procedures. These practice guidelines may help with decision making and patient management in areas where clinical evidence is absent or limited.
Collapse
Affiliation(s)
- Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Zurawia 14, 15-540 Białystok, Poland
| | - Krasimir Antonov
- Department of Gastroenterology, University Hospital ‘St. Ivan Rilski’, 1431 Sofia, Bulgaria;
| | - Pavel Drastich
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic;
| | - Peter Jarcuska
- Second Department of Internal Medicine, Faculty of Medicine and L. Pasteur University Hospital, P.J. Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia;
| | - Marina Maevskaya
- Clinic of Propedeutics of Internal Diseases, Gastroenterology and Hepatology Named after V. Kh. Vasilenko, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of Health of the Russian Federation, 119435 Moscow, Russia;
| | - Mihály Makara
- Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary;
| | - Željko Puljiz
- Department of Gastroenterology and Hepatology University Hospital Split, Split School of Medicine, 21000 Split, Croatia;
| | - Borut Štabuc
- Division of Internal Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia;
| | - Anca Trifan
- Department of Internal Diseases, Institute of Gastroenterology and Hepatology Lasi, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Lasi, Romania;
| |
Collapse
|
|
42
|
Antifungal Activity and Acute and Repeated-Dose Toxicity Study of Geranyl Cinnamate Ester in Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:3493625. [PMID: 34659431 PMCID: PMC8514914 DOI: 10.1155/2021/3493625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/03/2021] [Accepted: 09/14/2021] [Indexed: 11/17/2022]
Abstract
In the present study, the antifungal activity and toxicity of the geranyl cinnamate ester (GCE) were investigated. The GCE showed antifungal activity at a minimum concentration of 0.16 μL/mL against Candida albicans and at concentrations greater than 2.5 μL/mL against Aspergillus niger. In acute toxicity studies, the administration of GCE (2.000 mg/kg) affected the body weight gain and food intake but did not induce the mortality of the animals studied. After the investigation of repeated-dose toxicity of GCE at 2 and 4 mg/kg, the hematological and biochemical parameters were changed. In addition, the adrenal weight of male mice treated with GCE at 4 mg/kg was affected. In conclusion, according to the Organization for Economic Cooperation and Development (OECD) acute toxicity parameters, the geranyl cinnamate ester can be classified into safety category number 5. The results of this study suggested that the geranyl cinnamate ester may be a source of natural antifungals.
Collapse
|
|
43
|
Haddad TC, Zhao S, Li M, Patel SH, Johns A, Grogan M, Lopez G, Miah A, Wei L, Tinoco G, Riesenberg B, Li Z, Meara A, Bertino EM, Kendra K, Otterson G, Presley CJ, Owen DH. Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival. Cancer Immunol Immunother 2021; 71:1157-1165. [PMID: 34618180 PMCID: PMC9015999 DOI: 10.1007/s00262-021-03068-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/24/2021] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Immune checkpoint inhibitors (ICI) are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity; little data are available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI. METHODS We conducted a retrospective review of sequential cancer patients treated with ICI between 2011 and 2017 at our institution. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. We calculated the incidence of ≥ grade 3 irTCP and overall survival (OS). Patient factors associated with irTCP were assessed. RESULTS We identified 1,038 patients that met eligibility criteria. Overall, 89 (8.6%) patients developed grade ≥ 3 thrombocytopenia; eighteen were attributed to ICI (1.73% overall). Patients who developed grade ≥ 3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (4.17 vs. 10.8 month; HR. 1.94, 95% CI 1.13, 3.33; log-rank p = 0.0164). Patients with grade ≥ 3 irTCP also had worse survival compared to those without thrombocytopenia (4.17 vs. 13.31 months; HR 2.22, 95% CI 1.36, 3.62; log-rank p = 0.001). The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy (p = 0.059) and was not associated with cancer type, smoking status, age, gender, race, or line of therapy. CONCLUSIONS Unlike other irAEs, we found that irTCP was associated with worse overall survival. The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy.
Collapse
Affiliation(s)
- Tyler C Haddad
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Songzhu Zhao
- Center for Biostatistics, The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Mingjia Li
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Sandip H Patel
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Andrew Johns
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Madison Grogan
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Gabriella Lopez
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Abdul Miah
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Lai Wei
- Center for Biostatistics, The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Gabriel Tinoco
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Brian Riesenberg
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Zihai Li
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Alexa Meara
- Division of Rheumatology and Immunology, The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Erin M Bertino
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Kari Kendra
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Gregory Otterson
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Carolyn J Presley
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA
| | - Dwight H Owen
- Division of Medical Oncology, Department of Internal Medicine , The Ohio State University - James Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1335, Columbus, OH, 43210, USA.
| |
Collapse
|
|
44
|
Mataya LA, Srinivasan V, Rand EB, Alcamo AM. Multiple organ involvement and ICU considerations for the care of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in children. Transl Pediatr 2021; 10:2749-2762. [PMID: 34765498 PMCID: PMC8578785 DOI: 10.21037/tp-20-375] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 02/23/2021] [Indexed: 12/30/2022] Open
Abstract
Liver disease results in approximately 15,000 pediatric hospitalizations per year in the United States and is a significant burden to child health. Major etiologies of liver failure and indications for transplantation in children include: biliary atresia, metabolic/genetic conditions, toxins, infections, tumors, and immune-mediated liver/biliary injury. Children requiring transplantation are placed on the United Network of Organ Sharing waitlist including those with acute liver failure (ALF) and acute on chronic liver failure (ACLF). ALF is a clinical syndrome in which a previously healthy child develops rapid-onset hepatic dysfunction, and becomes critically ill with multiple organ dysfunction within days. ACLF, by contrast, is generally described as an acute decompensation of pre-existing chronic liver disease (CLD) brought on by a precipitating event, with higher risk of mortality. Children with ALF and ACLF receive multidisciplinary care in pediatric intensive care units (ICUs) due to multiple organ system involvement and high risk of decompensation in these patients. The care of these patients requires a holistic approach that addresses the complex interplay between hepatic and extra-hepatic organ systems. This review will define and describe ALF and ACLF in the pediatric population, and outline the effects of ALF and ACLF on individual organ systems with diagnostic and management considerations in the ICU while awaiting liver transplantation.
Collapse
Affiliation(s)
- Leslie A Mataya
- Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Vijay Srinivasan
- Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Elizabeth B Rand
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA
| | - Alicia M Alcamo
- Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania, Philadelphia, PA, USA
| |
Collapse
|
|
45
|
Kanikarla Marie P, Fowlkes NW, Afshar-Kharghan V, Martch SL, Sorokin A, Shen JP, Morris VK, Dasari A, You N, Sood AK, Overman MJ, Kopetz S, Menter DG. The Provocative Roles of Platelets in Liver Disease and Cancer. Front Oncol 2021; 11:643815. [PMID: 34367949 PMCID: PMC8335590 DOI: 10.3389/fonc.2021.643815] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 06/30/2021] [Indexed: 12/12/2022] Open
Abstract
Both platelets and the liver play important roles in the processes of coagulation and innate immunity. Platelet responses at the site of an injury are rapid; their immediate activation and structural changes minimize the loss of blood. The majority of coagulation proteins are produced by the liver—a multifunctional organ that also plays a critical role in many processes: removal of toxins and metabolism of fats, proteins, carbohydrates, and drugs. Chronic inflammation, trauma, or other causes of irreversible damage to the liver can dysregulate these pathways leading to organ and systemic abnormalities. In some cases, platelet-to-lymphocyte ratios can also be a predictor of disease outcome. An example is cirrhosis, which increases the risk of bleeding and prothrombotic events followed by activation of platelets. Along with a triggered coagulation cascade, the platelets increase the risk of pro-thrombotic events and contribute to cancer progression and metastasis. This progression and the resulting tissue destruction is physiologically comparable to a persistent, chronic wound. Various cancers, including colorectal cancer, have been associated with increased thrombocytosis, platelet activation, platelet-storage granule release, and thrombosis; anti-platelet agents can reduce cancer risk and progression. However, in cancer patients with pre-existing liver disease who are undergoing chemotherapy, the risk of thrombotic events becomes challenging to manage due to their inherent risk for bleeding. Chemotherapy, also known to induce damage to the liver, further increases the frequency of thrombotic events. Depending on individual patient risks, these factors acting together can disrupt the fragile balance between pro- and anti-coagulant processes, heightening liver thrombogenesis, and possibly providing a niche for circulating tumor cells to adhere to—thus promoting both liver metastasis and cancer-cell survival following treatment (that is, with minimal residual disease in the liver).
Collapse
Affiliation(s)
- Preeti Kanikarla Marie
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Natalie W Fowlkes
- Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Vahid Afshar-Kharghan
- Division of Internal Medicine, Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Stephanie L Martch
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Alexey Sorokin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - John Paul Shen
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Van K Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Nancy You
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Anil K Sood
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - David George Menter
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| |
Collapse
|
|
46
|
Desai S, Subramanian A. Thrombocytopenia in Chronic Liver Disease: Challenges and Treatment Strategies. Cureus 2021; 13:e16342. [PMID: 34277309 PMCID: PMC8276329 DOI: 10.7759/cureus.16342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2021] [Indexed: 12/14/2022] Open
Abstract
Thrombocytopenia is a common hematologic complication seen in patients with chronic liver disease (CLD). The pathophysiology of thrombocytopenia in CLD is multifactorial, primarily stemming from platelet sequestration and decreased platelet production. This review focuses on the pathophysiology and current treatment options in the treatment of thrombocytopenia in chronic liver disease. While platelet transfusions are the gold standard of treatment, considerations ought to be given to CLD patients who can benefit from transjugular intrahepatic portosystemic shunt and splenic artery embolization. Finally, the recent approval of thrombopoietin receptor agonists for use in CLD patients paves a way for a safe and effective alternative method of improving platelet levels and reducing the need for recurrent platelet transfusions.
Collapse
Affiliation(s)
- Shreya Desai
- Internal Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, USA
| | - Anita Subramanian
- Internal Medicine, Campbell University, Lilington, USA.,Internal Medicine, Ross University School of Medicine, Barbados, BRB
| |
Collapse
|
|
47
|
Influence of transfusions, hemodialysis and extracorporeal life support on hyperferritinemia in critically ill patients. PLoS One 2021; 16:e0254345. [PMID: 34252125 PMCID: PMC8274924 DOI: 10.1371/journal.pone.0254345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/25/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Ferritin is the major iron storage protein and an acute phase reactant. Hyperferritinemia is frequently seen in the critically ill where it has been hypothesized that not only underlying conditions but also factors such as transfusions, hemodialysis and extracorporeal life support (ECLS) lead to hyperferritinemia. This study aims to investigate the influence of transfusions, hemodialysis, and ECLS on hyperferritinemia in a multidisciplinary ICU cohort. METHODS This is a post-hoc analysis of a retrospective observational study including patients aged ≥ 18 years who were admitted to at least one adult ICU between January 2006 and August 2018 with hyperferritinemia ≥ 500 μg/L and of ≥ 14 days between two ICU ferritin measurements. Patients with hemophagocytic lymphohistiocytosis (HLH) were excluded. To identify the influence of transfusions, hemodialysis, and ECLS on ferritin change, multivariable linear regression analysis with ferritin change between two measurements as dependent variable was performed. RESULTS A total of 268 patients was analyzed. Median duration between measurements was 36 days (22-57). Over all patients, ferritin significantly increased between the first and last measurement (p = 0.006). Multivariable linear regression analysis showed no effect of transfusions, hemodialysis, or ECLS on ferritin change. Changes in aspartate aminotransferase (ASAT) and sequential organ failure assessment (SOFA) score were identified as influencing factors on ferritin change [unstandardized regression coefficient (B) = 2.6; (95% confidence interval (CI) 1.9, 3.3); p < 0.001 and B = 376.5; (95% CI 113.8, 639.1); p = 0.005, respectively]. Using the same model for subgroups of SOFA score, we found SOFA platelet count to be associated with ferritin change [B = 1729.3; (95% CI 466.8, 2991.9); p = 0.007]. No association of ferritin change and in-hospital mortality was seen in multivariable analysis. CONCLUSIONS The present study demonstrates that transfusions, hemodialysis, and ECLS had no influence on ferritin increases in critically ill patients. Hyperferritinemia appears to be less the result of iatrogenic influences in the ICU thereby underscoring its unskewed diagnostic value. TRIAL REGISTRATION The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
Collapse
|
|
48
|
Reusswig F, Fazel Modares N, Brechtenkamp M, Wienands L, Krüger I, Behnke K, Lee‐Sundlov MM, Herebian D, Scheller J, Hoffmeister KM, Häussinger D, Elvers M. Efficiently Restored Thrombopoietin Production by Ashwell-Morell Receptor and IL-6R Induced Janus Kinase 2/Signal Transducer and Activator of Transcription Signaling Early After Partial Hepatectomy. Hepatology 2021; 74:411-427. [PMID: 33369745 PMCID: PMC8236498 DOI: 10.1002/hep.31698] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 11/09/2020] [Accepted: 12/11/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Thrombocytopenia has been described in most patients with acute and chronic liver failure. Decreased platelet production and decreased half-life of platelets might be a consequence of low levels of thrombopoietin (TPO) in these patients. Platelet production is tightly regulated to avoid bleeding complications after vessel injury and can be enhanced under elevated platelet destruction as observed in liver disease. Thrombopoietin (TPO) is the primary regulator of platelet biogenesis and supports proliferation and differentiation of megakaryocytes. APPROACH AND RESULTS Recent work provided evidence for the control of TPO mRNA expression in liver and bone marrow (BM) by scanning circulating platelets. The Ashwell-Morell receptor (AMR) was identified to bind desialylated platelets to regulate hepatic thrombopoietin (TPO) production by Janus kinase (JAK2)/signal transducer and activator of transcription (STAT3) activation. Two-thirds partial hepatectomy (PHx) was performed in mice. Platelet activation and clearance by AMR/JAK2/STAT3 signaling and TPO production were analyzed at different time points after PHx. Here, we demonstrate that PHx in mice led to thrombocytopenia and platelet activation defects leading to bleeding complications, but unaltered arterial thrombosis, in these mice. Platelet counts were rapidly restored by up-regulation and crosstalk of the AMR and the IL-6 receptor (IL-6R) to induce JAK2-STAT3-TPO activation in the liver, accompanied by an increased number of megakaryocytes in spleen and BM before liver was completely regenerated. CONCLUSIONS The AMR/IL-6R-STAT3-TPO signaling pathway is an acute-phase response to liver injury to reconstitute hemostasis. Bleeding complications were attributable to thrombocytopenia and platelet defects induced by elevated PGI2 , NO, and bile acid plasma levels early after PHx that might also be causative for the high mortality in patients with liver disease.
Collapse
Affiliation(s)
- Friedrich Reusswig
- Clinic of Vascular and Endovascular SurgeryMedical Faculty and University HospitalDüsseldorfGermany
| | - Nastaran Fazel Modares
- Institute of Biochemistry and Molecular Biology II, Medical FacultyHeinrich‐Heine UniversityDüsseldorfGermany
| | - Marius Brechtenkamp
- Clinic of Vascular and Endovascular SurgeryMedical Faculty and University HospitalDüsseldorfGermany
| | - Leonard Wienands
- Clinic of Vascular and Endovascular SurgeryMedical Faculty and University HospitalDüsseldorfGermany
| | - Irena Krüger
- Clinic of Vascular and Endovascular SurgeryMedical Faculty and University HospitalDüsseldorfGermany
| | - Kristina Behnke
- Institute of Biochemistry and Molecular Biology II, Medical FacultyHeinrich‐Heine UniversityDüsseldorfGermany
| | | | - Diran Herebian
- Department of General Pediatrics, Neonatology and Pediatric CardiologyMedical FacultyHeinrich‐Heine‐UniversityDüsseldorfGermany
| | - Jürgen Scheller
- Institute of Biochemistry and Molecular Biology II, Medical FacultyHeinrich‐Heine UniversityDüsseldorfGermany
| | | | - Dieter Häussinger
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesMedical FacultyHeinrich‐Heine‐UniversityDüsseldorfGermany
| | - Margitta Elvers
- Clinic of Vascular and Endovascular SurgeryMedical Faculty and University HospitalDüsseldorfGermany
| |
Collapse
|
|
49
|
Miki N, Inoue S, Shibahara H, Kurazono K, Perard R, Tateishi R. A cost-effectiveness analysis of lusutrombopag for thrombocytopenia in patients with chronic liver disease in Japan. JGH OPEN 2021; 5:879-887. [PMID: 34386595 PMCID: PMC8341178 DOI: 10.1002/jgh3.12597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 06/06/2021] [Indexed: 11/16/2022]
Abstract
Background and Aim Thrombocytopenia is a frequent hematological condition in chronic liver disease (CLD) patients increasing the risk of bleeding in patients undergoing invasive procedures. Without an alternative, clinical guidelines recommended the use of platelet transfusion (PT) prior to procedure to prevent this bleeding risk. Lusutrombopag (LUSU), an orally active, small‐molecule thrombopoietin receptor agonist, was developed as an alternative to PT. The objective of this study was to evaluate a cost‐effectiveness of LUSU as a potential alternative to PT in Japan. Methods A cost‐effectiveness analysis of LUSU relative to PT was conducted by a simulation model consisting of a decision tree combined to Markov model. Quality‐adjusted life years (QALYs) were used as an indicator of efficacy, and the analysis was conducted from the Japanese public healthcare payer's perspective. The time horizon of the analysis was 50 years (a lifetime) and the discount rate was set at 2%. Results LUSU gained 6.1803 QALYs with an expected lifetime costs of 2 380 219 JPY compared to PT with 6.1712 QALYs gained and expected lifetime costs of 2 382 908 JPY. Thus, LUSU was deemed dominant compared with PT. Based on probabilistic analyses, the chance of LUSU being dominant and the incremental cost‐effectiveness ratio being below 5 million JPY/QALY was estimated at 51.8% and 78.3%, respectively, demonstrating the robustness of the results. Conclusions LUSU was evaluated as an efficacious and cost‐saving treatment option for Japanese CLD patients with thrombocytopenia who required a planned invasive procedure compared with PT and economically should be considered as an alternative treatment.
Collapse
|
|
50
|
Giannini EG, Kano T, Ochiai T, Bentley R, Shrestha P, Afdhal N. Bleeding events in lusutrombopag-treated thrombocytopenic patients. Eur J Clin Invest 2021; 51:e13503. [PMID: 33523482 PMCID: PMC8243945 DOI: 10.1111/eci.13503] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/22/2021] [Accepted: 01/26/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy
| | - Takeshi Kano
- Global Project Management Department, Shionogi & Co., Ltd., Osaka, Japan
| | | | - Roy Bentley
- US Global Market Access, Shionogi Inc., Florham Park, NJ, USA
| | - Pomy Shrestha
- Product Safety and Pharmacovigilance, Shionogi Inc., Florham Park, NJ, USA
| | - Nezam Afdhal
- Liver Center, Beth Israel Deaconess Medical Center, Boston, MA, USA
| |
Collapse
|