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Roy A, Kumar Y, Verma N. Coagulopathy in acute liver failure. Best Pract Res Clin Gastroenterol 2024; 73:101956. [PMID: 39709211 DOI: 10.1016/j.bpg.2024.101956] [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: 09/24/2024] [Accepted: 10/22/2024] [Indexed: 12/23/2024]
Abstract
Acute liver failure (ALF) is a rare but rapidly progressing syndrome, marked by severe liver dysfunction and altered mental status. While definitions of ALF vary across different guidelines, with timelines ranging from 4 to 26 weeks between jaundice onset and encephalopathy, the key defining features remain encephalopathy and coagulopathy. Elevated coagulation markers, particularly prothrombin time and international normalized ratio, have traditionally been associated with bleeding risks. However, emerging evidence suggests a rebalanced state of coagulation in ALF, similar to cirrhosis, where bleeding risks-both spontaneous and procedural-are surprisingly low. Viscoelastic hemostatic assays and thrombin generation assays further confirm this rebalanced hemostatic state. Current guidelines for correcting coagulopathy in ALF remain limited, typically reserved for active bleeding or prior to high-risk invasive procedures.
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Affiliation(s)
- Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multi-speciality Hospitals, Kolkatta, India
| | - Yogendra Kumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Sokou R, Parastatidou S, Konstantinidi A, Tsantes AG, Iacovidou N, Piovani D, Bonovas S, Tsantes AE. Bleeding Scoring Systems in Neonates: A Systematic Review. Semin Thromb Hemost 2024; 50:620-637. [PMID: 38016650 DOI: 10.1055/s-0043-1777070] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2023]
Abstract
We conducted a systematic review aiming to summarize the data on the current hemorrhage prediction models and evaluate their potential for generalized application in the neonatal population. The electronic databases PubMed and Scopus were searched, up to September 20, 2023, for studies that focused on development and/or validation of a prediction model for bleeding risk in neonates, and described the process of model building. Nineteen studies fulfilled the inclusion criteria for the present review. Eighteen bleeding risk prediction models in the neonatal population were identified, four of which were internally validated, one temporally and one externally validated. The existing prediction models for neonatal hemorrhage are mostly based on clinical variables and do not take into account the clinical course and hemostatic profile of the neonates. Most studies aimed at predicting the risk of intraventricular hemorrhage (IVH) reflecting the fact that IVH is the most frequent and serious bleeding complication in preterm neonates. A justification for the study sample size for developing the prediction model was given only by one study. Prediction and stratification of risk of hemorrhage in neonates is yet to be optimized. To this end, qualitative standards for model development need to be further improved. The assessment of the risk of bleeding incorporating platelet count, coagulation parameters, and a set of relevant clinical variables is crucial. Large, rigorous, collaborative cohort studies are warranted to develop a robust prediction model to inform the need for transfusion, which is a fundamental step towards personalized transfusion therapy in neonates.
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Affiliation(s)
- Rozeta Sokou
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikea, Piraeus, Greece
| | | | | | - Andreas G Tsantes
- Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Nicoletta Iacovidou
- Neonatal Department, Aretaeio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Milan, Italy
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Milan, Italy
| | - Argirios E Tsantes
- Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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Boldt D, Busse L, Chawla LS, Flannery AH, Khanna A, Neyra JA, Palmer P, Wilson J, Yessayan L. Anticoagulation practices for continuous renal replacement therapy: a survey of physicians from the United States. Ren Fail 2023; 45:2290932. [PMID: 38073554 PMCID: PMC11001369 DOI: 10.1080/0886022x.2023.2290932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 11/29/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND During continuous renal replacement therapy (CRRT), anticoagulants are recommended for patients at low risk of bleeding and not already receiving systemic anticoagulants. Current anticoagulants used in CRRT in the US are systemic heparins or regional citrate. To better understand use of anticoagulants for CRRT in the US, we surveyed nephrologists and critical care medicine (CCM) specialists. METHODS The survey contained 30 questions. Respondents were board certified and worked in intensive care units of academic medical centers or community hospitals. RESULTS 150 physicians (70 nephrologists and 80 CCM) completed the survey. Mean number of CRRT machines in use increased ∼30% from the pre-pandemic era to 2022. Unfractionated heparin was the most used anticoagulant (43% of estimated patients) followed by citrate (28%). Respondents reported 29% of patients received no anticoagulant. Risk of hypocalcemia (52%) and citrate safety (42%) were the predominant reasons given for using no anticoagulant instead of citrate in heparin-intolerant patients. 84% said filter clogging was a problem when no anticoagulant was used, and almost 25% said increased transfusions were necessary. Respondents using heparin (n = 131) considered it inexpensive and easily obtainable, although of moderate safety, citing concerns of heparin-induced thrombocytopenia and bleeding. Anticoagulant citrate dextrose solution was the most used citrate. Respondents estimated that 37% of patients receiving citrate develop hypocalcemia and 17% citrate lock. CONCLUSIONS Given the increased use of CRRT and the lack of approved, safe, and effective anticoagulant choices for CRRT in the US, effective use of current and other anticoagulant options needs to be evaluated.
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Affiliation(s)
- David Boldt
- Department of Anesthesiology and Perioperative Medicine, UCLA Healthcare System and David Geffen School of Medicine, Los Angeles, CA, USA
| | - Laurence Busse
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA
| | | | - Alexander H. Flannery
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY, USA
| | - Ashish Khanna
- Department of Anesthesiology, Section on Critical Care Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA
- Perioperative Outcomes and Informatics Collaborative, Winston-Salem, NC, USA
- Outcomes Research Consortium, Cleveland, OH, USA
| | - Javier A. Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - James Wilson
- Department of Nephrology, UCLA Healthcare System and David Geffen School of Medicine, Los Angeles, CA, USA
| | - Lenar Yessayan
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
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Sohail MA, Vachharajani TJ, Lane JE, Huang S, Wang X, Mucha S, Kapoor A, Dugar S, Hanane T. Thromboelastography-Guided Correction of Coagulopathy Before Tunneled Central Venous Access in Critically Ill Patients With Liver Disease: A Propensity Score-Matched Study. Crit Care Explor 2023; 5:e1023. [PMID: 38115819 PMCID: PMC10730036 DOI: 10.1097/cce.0000000000001023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2023] Open
Abstract
Importance Optimal blood product transfusion strategies before tunneled central venous catheter (CVC) placement are required in critically ill coagulopathic patients with liver disease to reduce exposure to allogeneic blood products and mitigate bleeding and thrombotic complications. Objectives This study evaluated the safety and efficacy of a thromboelastography-guided transfusion strategy for the correction of coagulopathy in patients with liver disease compared with a conventional transfusion strategy (using international normalized ratio, platelet count, and fibrinogen) before tunneled CVC insertion. Design Setting and Participants A retrospective propensity score-matched single-center cohort study was conducted at a quaternary care academic medical center involving 364 patients with liver disease (cirrhosis and acute liver failure) who underwent tunneled CVC insertion in the ICU. Patients were stratified into two groups based on whether they received blood product transfusions based on a thromboelastography-guided or conventional transfusion strategy. Main Outcomes and Measures Primary outcomes that were evaluated included the volume, units and cost of blood products (fresh frozen plasma, cryoprecipitate, and platelets) when using a thromboelastography-guided or conventional approach to blood transfusions. Secondary outcomes included the frequency of procedure-related bleeding and thrombotic complications. Results The total number of units/volume/cost of fresh frozen plasma (12 U/3,000 mL/$684 vs. 32 U/7,500 mL/$1,824 [p = 0.019]), cryoprecipitate (60 U/1,500 mL/$3,240 vs. 250 U/6,250 mL/$13,500 [p < 0.001]), and platelets (5 U/1,500 mL/$2,610 vs. 13 units/3,900 mL/$6,786 [p = 0.046]) transfused were significantly lower in the thromboelastography-guided transfusion group than in the conventional transfusion group. No differences in the frequency of bleeding/thrombotic events were observed between the two groups. Conclusions and Relevance A thromboelastography-guided transfusion strategy for correction of coagulopathy in critically ill patients with liver disease before tunneled CVC insertion, compared with a conventional transfusion strategy, reduces unnecessary exposure to allogeneic blood products and associated costs without increasing the risk for peri-procedural bleeding and thrombotic complications.
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Affiliation(s)
- Mohammad A Sohail
- Department of Kidney Medicine, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Tushar J Vachharajani
- Department of Medicine, John D. Dingell Department of VA Medical Center, Detroit, MI
- Department of Medicine, Wayne State University School of Medicine, Detroit, MI
| | - James E Lane
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Shuaiqi Huang
- Department of Quantitative Health Sciences at Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Xiaofeng Wang
- Department of Quantitative Health Sciences at Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Simon Mucha
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Aanchal Kapoor
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Siddharth Dugar
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Tarik Hanane
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH
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Pejchinovski I, Turkkan S, Pejchinovski M. Recent Advances of Proteomics in Management of Acute Kidney Injury. Diagnostics (Basel) 2023; 13:2648. [PMID: 37627907 PMCID: PMC10453063 DOI: 10.3390/diagnostics13162648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/31/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
Acute Kidney Injury (AKI) is currently recognized as a life-threatening disease, leading to an exponential increase in morbidity and mortality worldwide. At present, AKI is characterized by a significant increase in serum creatinine (SCr) levels, typically followed by a sudden drop in glomerulus filtration rate (GFR). Changes in urine output are usually associated with the renal inability to excrete urea and other nitrogenous waste products, causing extracellular volume and electrolyte imbalances. Several molecular mechanisms were proposed to be affiliated with AKI development and progression, ultimately involving renal epithelium tubular cell-cycle arrest, inflammation, mitochondrial dysfunction, the inability to recover and regenerate proximal tubules, and impaired endothelial function. Diagnosis and prognosis using state-of-the-art clinical markers are often late and provide poor outcomes at disease onset. Inappropriate clinical assessment is a strong disease contributor, actively driving progression towards end stage renal disease (ESRD). Proteins, as the main functional and structural unit of the cell, provide the opportunity to monitor the disease on a molecular level. Changes in the proteomic profiles are pivotal for the expression of molecular pathways and disease pathogenesis. Introduction of highly-sensitive and innovative technology enabled the discovery of novel biomarkers for improved risk stratification, better and more cost-effective medical care for the ill patients and advanced personalized medicine. In line with those strategies, this review provides and discusses the latest findings of proteomic-based biomarkers and their prospective clinical application for AKI management.
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Affiliation(s)
- Ilinka Pejchinovski
- Department of Quality Assurance, Nikkiso Europe GmbH, 30885 Langenhagen, Germany; (I.P.); (S.T.)
| | - Sibel Turkkan
- Department of Quality Assurance, Nikkiso Europe GmbH, 30885 Langenhagen, Germany; (I.P.); (S.T.)
| | - Martin Pejchinovski
- Department of Analytical Instruments Group, Thermo Fisher Scientific, 82110 Germering, Germany
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Liu J, Liu Z, Zhao T, Su T, Jin Q. Thromboelastography and Traditional Coagulation Testing in Non-ICU-Admitted Patients with Acute Kidney Injury: An Observational Cohort Study. Am J Nephrol 2023; 54:208-218. [PMID: 37364534 DOI: 10.1159/000530777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 04/05/2023] [Indexed: 06/28/2023]
Abstract
INTRODUCTION This study aimed to elucidate the coagulation disorders in non-ICU patients with acute kidney injury (AKI) and their contribution to clotting-related outcomes of intermittent kidney replacement therapy (KRT). METHODS We included non-ICU-admitted patients with AKI requiring intermittent KRT, clinically having a risk of bleeding and against systemic anticoagulant use during KRT between April and December 2018. The premature termination of treatment due to circuit clotting was considered a poor outcome. We analyzed the characteristics of thromboelastography (TEG)-derived and traditional coagulation parameters and explored the potential-affecting factors. RESULTS In total, 64 patients were enrolled. Hypocoagulability was detected in 4.7%-15.6% of patients by a combination of the traditional parameters, i.e., prothrombin time (PT)/international normalized ratio, activated partial PT, and fibrinogen. No patient had hypocoagulability observed on TEG-derived reaction time; only 2.1%, 3.1%, and 10.9% of patients had hypocoagulability on TEG-derived kinetic time (K-time), α-angle, and maximum amplitude (MA), respectively, which were also platelet-related coagulation parameters, despite 37.5% of the cohort having thrombocytopenia. In contrast, hypercoagulability was more prevalent, involving 12.5%, 43.8%, 21.9%, and 48.4% of patients on TEG K-time, α-angle, MA, and coagulation index (CI), respectively, although thrombocytosis was only in 1.5% of the cohort. Patients with thrombocytopenia showed lower fibrinogen level (2.6 vs. 4.0 g/L, p = 0.00), α-angle (63.5° vs. 73.3°, p = 0.00), MA (53.5 vs. 66.1 mm, p = 0.00), and CI (1.8 vs. 3.6, p = 0.00) but higher thrombin time (17.8 vs. 16.2 s, p = 0.00) and K-time (2.0 vs. 1.2 min, p = 0.00) than those with a platelet count over 100 × 109/L. 41 patients were treated with heparin-free protocol, and 23 were treated with regional citrate anticoagulation (RCA). The premature termination rate was 41.5% on heparin-free patients, while 8.7% of patients underwent an RCA protocol (p = 0.006). Heparin-free protocol was the strongest adverse factor to poor outcomes. A heparin-free subgroup analysis found that the circuit clotting risk was increased by 61.7% with a 10 × 109/L elevation in platelet count (odds ratio [OR] = 1.617, p = 0.049) and decreased by 67.5% following a second increase of PT (OR = 0.325, p = 0.041). No significant correlation was found between TEG parameters and premature circuit clotting. CONCLUSIONS Most non-ICU-admitted patients with AKI had normal-to-enhanced hemostasis and activated platelet function based on TEG results, as well as a high rate of premature circuit clotting when receiving heparin-free protocol despite thrombocytopenia. Further studies are needed to better determine the use of TEG in respect to management of anticoagulation and bleeding complications in AKI patients with KRT.
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Affiliation(s)
- Jiajia Liu
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
| | - Zhongyuan Liu
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
| | - Tao Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
| | - Tao Su
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
| | - Qizhuang Jin
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
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Zanetto A, Northup P, Roberts L, Senzolo M. Haemostasis in cirrhosis: Understanding destabilising factors during acute decompensation. J Hepatol 2023; 78:1037-1047. [PMID: 36708812 DOI: 10.1016/j.jhep.2023.01.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/03/2023] [Accepted: 01/17/2023] [Indexed: 01/27/2023]
Abstract
Hospitalised patients with decompensated cirrhosis are in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic pathways. However, this rebalanced haemostatic state is highly susceptible to perturbations and may easily tilt towards hypocoagulability and bleeding. Acute kidney injury, bacterial infections and sepsis, and progression from acute decompensation to acute-on-chronic liver failure are associated with additional alterations of specific haemostatic pathways and a higher risk of bleeding. Unfortunately, there is no single laboratory method that can accurately stratify an individual patient's bleeding risk and guide pre-procedural prophylaxis. A better understanding of haemostatic alterations during acute illness would lead to more rational and individualised management of hospitalised patients with decompensated cirrhosis. This review will outline the latest findings on haemostatic alterations driven by acute kidney injury, bacterial infections/sepsis, and acute-on-chronic liver failure in these difficult-to-treat patients and provide evidence supporting more tailored management of bleeding risk.
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Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Patrick Northup
- Division of Gastroenterology and Hepatology, NYU Grossman School of Medicine, NYU Transplant Institute, New York, NY, USA
| | - Lara Roberts
- King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital, London, UK
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
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Chen B, Liu J, Li Y, He X, Zhou C, Chen Y, Zheng M. Elevated D-Dimer levels correlate with the development of hepatorenal syndrome and a poor outcome in patients with cirrhosis. Scand J Gastroenterol 2022; 57:1486-1493. [PMID: 35833837 DOI: 10.1080/00365521.2022.2098051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Whether hemostatic status was correlated with the diverse types of acute kidney injury in cirrhotic patients is unclear. The present study aimed to investigate the relationship between hemostatic markers and the diverse types of acute kidney injury (AKI) in liver cirrhosis. PATIENTS AND METHODS Cirrhotic patients with consecutive treatment at the First Affiliated Hospital of Medicine School, Zhejiang University, were pooled in a cohort. Their demographic and clinical data, biochemistry parameters and hemostatic markers were assessed to identify risk factors for the development and prognosis of AKI. RESULTS A total of 773 cirrhotic patients were included in this cohort. Patients with hepatorenal syndrome (HRS) had significantly higher D-Dimer than those with the other types of AKI. In univariate COX regression, APTT, TT, INR, D-Dimer and Fib were correlated with the development of AKI, HRS and acute tubular necrosis (ATN), however, only D-Dimer remained independently associated with the development of AKI and HRS in multivariate COX regression. The area under the ROC curve of D-Dimer was 0.755 (95%CI, 0.718-0.793) in predicting the development of AKI, 0.879 (95%CI, 0.791-0.967) in predicting the development of HRS, respectively. D-Dimer was used for diagnosis of HRS with a sensitivity of 87.3% and specificity of 72.9% at the cutoff of 3.7 (mg/L FEU). Survival rates differed significantly between groups by D-Dimer level. CONCLUSIONS Hemostatic markers were significantly associated with the diverse types of AKI. D-Dimer was an independent risk factor for HRS and correlated with a poor outcome in cirrhotic patients.
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Affiliation(s)
- Baode Chen
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Liu
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yongtao Li
- Department of infectious disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xuelin He
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Cheng Zhou
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yu Chen
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Min Zheng
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Jensen JLS, Hviid CVB, Hvas CL, Christensen S, Hvas AM, Larsen JB. Platelet Function in Acute Kidney Injury: A Systematic Review and a Cohort Study. Semin Thromb Hemost 2022. [PMID: 36174606 DOI: 10.1055/s-0042-1757167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Acute kidney injury (AKI) patients have increased bleeding risk, which could be partially due to acquired platelet dysfunction. We conducted a systematic review and a cohort study to investigate platelet function and count in AKI and their association with AKI-related bleeding and mortality. Through a systematic literature search in PubMed and Embase, we identified 9 studies reporting platelet function and 56 studies reporting platelet count or platelet indices in AKI patients. Overall, platelet aggregation was reduced in AKI patients in nonintensive care unit (ICU) settings but not in ICU settings, except that reduced aggregation was associated with renal replacement therapy. Thrombocytopenia in AKI was frequent and often predictive of mortality. In our cohort study, we prospectively included 54 adult ICU patients who developed AKI within 24 hours of ICU admission and 33 non-AKI ICU controls. Platelet function was measured with light transmission aggregometry and flow cytometry. AKI patients bled more frequently than non-AKI patients (p = 0.04), and bleeding was associated with increased 30-day mortality in AKI (p = 0.02). However, platelet function was not different between AKI and non-AKI patients (aggregation: all p > 0.52; flow cytometry: all p > 0.07) and platelet function was not associated with bleeding in AKI. In conclusion, a reduced platelet count is frequent in AKI, but the literature on platelet function in AKI is sparse. In a cohort study, we demonstrated that patients with AKI within 24 hours of ICU admission exhibited increased bleeding tendency but this was not associated with reduced platelet function.
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Affiliation(s)
| | - Claus Vinter Bødker Hviid
- Department of Clinical Biochemistry, Thrombosis and Haemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - Christine Lodberg Hvas
- Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Steffen Christensen
- Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anne-Mette Hvas
- Department of Clinical Biochemistry, Thrombosis and Haemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Julie Brogaard Larsen
- Department of Clinical Biochemistry, Thrombosis and Haemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
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Sudusinghe D, Riddell A, Gandhi T, Chowdary P, Davenport A. Increased risk of dialysis circuit clotting in hemodialysis patients with COVID-19 is associated with elevated FVIII, fibrinogen and D-dimers. Hemodial Int 2022; 27:38-44. [PMID: 36081392 PMCID: PMC9537782 DOI: 10.1111/hdi.13046] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 08/09/2022] [Accepted: 08/23/2022] [Indexed: 01/28/2023]
Abstract
INTRODUCTION Severe COVID-19 infections increase the risk of thrombotic events and Intensive Care Units reported increased extracorporeal circuit clotting (ECC) in COVID-19 patients with acute kidney injury. We wished to determine whether hemodialysis (HD) patients with COVID-19 also have increased risk of circuit clotting. METHODS We reviewed coagulation studies and HD records, 4 weeks before and after COVID-19 polymerase chain reaction detection in HD patients between April 2020 and June 2021. FINDINGS Sixty-eight (33.5%) of 203 HD patients with COVID-19, 65% male, mean age 64.9 ± 15.3 years, experienced some circuit clotting, and no clotting recorded prior to positive test results. In those who experienced ECC, prothrombin, activated partial thromboplastin or thrombin times were not different, whereas median factor VIII (273 [168-419] vs. 166 [139-225] IU/dl, p < 0.001), D-dimers (2654 [1381-6019] vs. 1351 [786-2334] ng/ml, p < 0.05), and fibrinogen (5.6 ± 1.4 vs. 4.9 ± 1.4 g/L, p < 0.05) were greater. Antithrombin (94 [83-112] vs. 89 [84-103] IU/dl), protein C (102 [80-130] vs. 86 [76-106] IU/dl), protein S (65 [61-75] vs. 65 [52-79] IU/dl) and platelet counts (193 [138-243] vs. 174 [138-229] × 109 /L) did not differ. On multivariable logistic analysis, circuit clotting was associated with log factor VIII (odds ratio [OR] 14.8 (95% confidence limits [95% CL] 1.12-19.6), p = 0.041), fibrinogen (OR 1.57 [95% CL 1.14-21.7], p = 0.006) and log D dimer (OR 4.8 [95% CL 1.16-12.5], p = 0.028). DISCUSSION Extracorporeal circuit clotting was increased within 4 weeks of testing positive for COVID-19. Clotting was associated with increased factor VIII, fibrinogen and D-dimer, suggesting that the risk of circuit clotting was related to the inflammatory response to COVID-19.
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Affiliation(s)
- Dinesha Sudusinghe
- Department of Physiology, Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka
| | - Anne Riddell
- Haemophilia and Thrombosis Laboratory (Health Services Laboratories)Royal Free HospitalLondonUK,Katharine Dormandy Haemophilia and Thrombosis CentreRoyal Free HospitalLondonUK
| | - Tejas Gandhi
- Haemophilia and Thrombosis Laboratory (Health Services Laboratories)Royal Free HospitalLondonUK
| | - Pratima Chowdary
- Katharine Dormandy Haemophilia and Thrombosis CentreRoyal Free HospitalLondonUK,Research Department of HaematologyCancer Institute UCLLondonUK
| | - Andrew Davenport
- Department of Renal Medicine, Royal Free Hospital, Faculty of Medical SciencesUniversity College LondonLondonUK
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Panholzer B, Pilarczyk K, Huenges K, Aldinger C, Friedrich C, Nowak-Göttl U, Cremer J, Haneya A. Severe Pulmonary Bleeding after Assist Device Implantation: Incidence, Risk Factors and Prognostic Impact. J Clin Med 2022; 11:1908. [PMID: 35407516 PMCID: PMC8999887 DOI: 10.3390/jcm11071908] [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: 01/18/2022] [Revised: 03/03/2022] [Accepted: 03/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Continuous flow left ventricular assist devices (CF-LVAD) improve survival in patients with advanced heart failure but confer risk of bleeding complications. Whereas pathophysiology and risk factors for many bleeding complications are well investigated, the literature lacks reports about pulmonary bleeding. Therefore, it was the aim of the present study to assess incidence, risk factors, and clinical relevance of pulmonary bleeding episodes after LVAD implantation. Methods: We retrospectively analyzed our institutional database of 125 consecutive patients who underwent LVAD implantation between 2008 and 2017. Demographic and clinical variables related to bleeding were collected. The primary endpoint was incidence of severe pulmonary bleeding (SPB). Results: Nine out of 125 patients suffered from SPB during the postoperative course (7.2%) 11 days after surgery in the median. None of them had a known history of lung disease or bleeding disorder. History of prior myocardial infarction (0% vWD. 42.2%, p = 0.012) and ischemic cardiomyopathy (25.0% vs. 50.0%, p = 0.046) were less frequent in the SBP group. Concomitant aortic valve replacement was more common in the group with SPB (33.3% versus 7.0%, p = 0.034). Surgical (blood loss 9950 vs. 3800 mL, p = 0.012) as well as ear-nose-throat (ENT) bleedings (33% vs. 4.6%, p = 0.015) were observed more frequently in patients with SPB. SPB was associated with a complicated postoperative course with a higher incidence of acute kidney failure (100% versus 36.7%, p = 0.001) and delirium (44.4% versus 14.8%, p = 0.045); a higher need for red blood cell (26 packs versus 7, p < 0.001), fresh frozen plasma (18 units versus 6, p = 0.002), and platelet transfusion (8 pools versus 1, p = 0.001); longer ventilation time (1206 versus 171 h, p = 0.001); longer ICU-stay (58 versus 13 days, p = 0.002); and higher hospital mortality (66.7% vs. 29%, p = 0.029). Conclusion: SPB is a rare but serious complication after LVAD implantation and is significantly associated with higher morbidity and mortality. The pathophysiology and potential risk factors are unknown but may include coagulation disorders and frequent suctioning or empiric bronchoscopy causing airway irritation.
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Affiliation(s)
- Bernd Panholzer
- Department of Cardiovascular Surgery, University of Schleswig-Holstein, 24105 Kiel, Germany; (B.P.); (K.H.); (C.A.); (C.F.); (J.C.); (A.H.)
| | - Kevin Pilarczyk
- Department of Intensive Care Medicine, Imland Klinik Rendsburg, 24768 Rendsburg, Germany
| | - Katharina Huenges
- Department of Cardiovascular Surgery, University of Schleswig-Holstein, 24105 Kiel, Germany; (B.P.); (K.H.); (C.A.); (C.F.); (J.C.); (A.H.)
| | - Charlotte Aldinger
- Department of Cardiovascular Surgery, University of Schleswig-Holstein, 24105 Kiel, Germany; (B.P.); (K.H.); (C.A.); (C.F.); (J.C.); (A.H.)
| | - Christine Friedrich
- Department of Cardiovascular Surgery, University of Schleswig-Holstein, 24105 Kiel, Germany; (B.P.); (K.H.); (C.A.); (C.F.); (J.C.); (A.H.)
| | - Ulrike Nowak-Göttl
- Institute of Clinical Chemistry, University of Schleswig-Holstein, 24105 Kiel, Germany;
| | - Jochen Cremer
- Department of Cardiovascular Surgery, University of Schleswig-Holstein, 24105 Kiel, Germany; (B.P.); (K.H.); (C.A.); (C.F.); (J.C.); (A.H.)
| | - Assad Haneya
- Department of Cardiovascular Surgery, University of Schleswig-Holstein, 24105 Kiel, Germany; (B.P.); (K.H.); (C.A.); (C.F.); (J.C.); (A.H.)
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12
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Effects of Gymnema inodorum Leaf Extract on the Alteration of Blood Coagulation Parameters and Platelet Count in Plasmodium berghei-Infected Mice. J Parasitol Res 2022; 2022:4225682. [PMID: 35310010 PMCID: PMC8933115 DOI: 10.1155/2022/4225682] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 03/01/2022] [Indexed: 11/18/2022] Open
Abstract
Malaria remains highly prevalent and one of the major causes of morbidity and mortality in tropical and subtropical regions. Alteration of blood coagulation and platelets has played an important role and attributed to increased morbidity in malaria. Hence, this study was performed to investigate the efficacy of Gymnema inodorum leaf extract on Plasmodium berghei-induced alteration of blood coagulation parameters and platelet numbers in mice. Groups of ICR mice were inoculated with 1 × 107 parasitized red blood cells of P. berghei ANKA (PbANKA) and given orally by gavage with 100, 250, and 500 mg/kg of G. inodorum leaf extract (GIE). Chloroquine (10 mg/kg) was used as a positive control. Platelet count and blood coagulation parameters were measured. The results showed that PbANKA induced thrombocytopenia in mice as indicated by markedly decreased platelet count. Decreased platelet count had a negative correlation with the degree of parasitemia with R2 value of 0.6668. Moreover, significantly (p < 0.05) shortened activated partial thromboplastin time was found in PbANKA-infected group, while prothrombin time and thrombin time were still normal. GIE gave significantly (p < 0.05) good results with respect to platelet count, compared with the results obtained from positive and healthy controls. Additionally, GIE reversed the alteration of blood coagulation parameters when compared to untreated mice. The highest efficacy of GIE was observed at a dose of 500 mg/kg. It was concluded that GIE exerted a protective effect on thrombocytopenia and altered blood coagulation parameters induced by PbANKA infection in mice. This plant may be a future candidate for alternative antimalarial development.
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13
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Riddell A, Chowdary P, Davenport A. The effect of SARS-Co-V2 infection on prothrombotic and anticoagulant factors in dialysis patients. Artif Organs 2022; 46:1328-1333. [PMID: 35167146 PMCID: PMC9111238 DOI: 10.1111/aor.14206] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 01/11/2022] [Accepted: 02/01/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND Patients with COVID-19 infection are at increased risk of thrombosis. We wished to determine whether this was is due to an increase in prothrombotic or reduction in anticoagulant factors, and whether heparin would be an appropriate anticoagulant. METHODS We measured routine coagulation and prothrombtic factors in dialysis patients after a positive COVID-19 test between March 2020 -April 2021. RESULTS Routine coagulation tests were measured in 227 dialysis patients, 148 males (65.2%), median age 67.5 (53.8-77.0) years. The international normalised ratio was prolonged in 11.5%, activated partial thromboplastin time in 48.5%, thrombin time in 57%. Factor VIII was increased in 59.1%, fibrinogen in 73.8%, and D-dimer 95.5%. Protein C was reduced in 15.3%, protein S in 28%, and antithrombin (AT) in 12.1%. Two patients were Lupus anticoagulant positive , and two Factor VLeiden positive. Factor VIII levels increased with clinical disease; outpatients 159 (136-179) IU/dL, hospitalised but not ventilated 228 (167-311) IU, ventilated 432 (368-488) IU/dL (p<0.01). Overall 75% had an AT level ≥ 88 IU/dL (reference range 79-106), but only 11.7% of non-hospitalised patientscompared to 45% of those who died, p<0.01, Fibrinogen,D-dimers, proteins S or C did not differ with clinical disease severity, whether patients required hospital admission or not and between survivors and those who died. CONCLUSION COVID-19 dialysis patients have increased levels of fibrinogen and D-Dimers, but only factor VIII levels in the clotting profile increased with clinical disease severity increasing systemic hypercoagulability. AT concentrations are maintained and as such should not compromise anticoagulation with heparins.
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Affiliation(s)
- Anne Riddell
- Haemophilia & Thrombosis Laboratory (Health Services Laboratories), Royal Free Hospital, London, UK
| | - Pratima Chowdary
- Katharine Dormandy Haemophilia & Thrombosis Centre, Royal Free Hospital.,Research Department of Haematology, Cancer Institute UCL
| | - Andrew Davenport
- UCL Department of Nephrology, Royal Free Hospital, Faculty of Medical Sciences, University College London, London, UK
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14
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Davenport A, Honore PM. Continuous renal replacement therapy under special conditions like sepsis, burn, cardiac failure, neurotrauma, and liver failure. Semin Dial 2021; 34:457-471. [PMID: 34448261 DOI: 10.1111/sdi.13002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/25/2021] [Accepted: 05/01/2021] [Indexed: 12/19/2022]
Abstract
Continuous renal replacement therapy (CRRT) in sepsis does have a role in removing excessive fluid, and also role in removal of mediators although not proven today, and to allow fluid space in order to feed. In these conditions, continuous renal replacement therapy can improve morbidity but never mortality so far. Regarding sepsis, timing has become a more important issue after decades and is currently more discussed than dosing. Rationale of blood purification has evolved a lot in the last years regarding sepsis with the discovery of many types of sorbent allowing ideas from science fiction to become reality in 2021. Undoubtedly, COVID-19 has reactivated the interest of blood purification in sepsis but also in COVID-19. Burn is even more dependent about removal of excessive fluid as compared to sepsis. Regarding cardiac failure, ultrafiltration can improve the quality of life and morbidity when diuretics are becoming inefficient but can never improve mortality. Regarding brain injury, CRRTs have several advantages as compared to intermittent hemodialysis. In liver failure, there have been no randomized controlled trials to examine whether single-pass albumin dialysis offers advantages over standard supportive care, and there is always the cost of albumin.
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Affiliation(s)
| | - Patrick M Honore
- ICU Department, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, ULB University, Brussels, Belgium
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15
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Dronamraju SS, Gaidhane SA, Mahalaqqa KN, Gaidhane AM, Andhale AG, Quazi ZS. Splenic Artery Embolization in Subcapsular Splenic Hematoma Secondary to Dengue Hemorrhagic Fever. J Glob Infect Dis 2021; 13:145-147. [PMID: 34703156 PMCID: PMC8491811 DOI: 10.4103/jgid.jgid_140_20] [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: 05/14/2020] [Revised: 09/09/2020] [Accepted: 02/24/2021] [Indexed: 11/04/2022] Open
Abstract
Dengue hemorrhagic fever (DHF) is a common syndrome of dengue viral infection but complications such as sub-capsular splenic hematoma leading to capsular rupture in dengue are rare. We report a case of a young male who presented with fever, breathlessness, and acute abdomen. His CT of the abdomen revealed subcapsular splenic hematoma measuring 16.7 cm × 13.0 cm × 11 cm. His laboratory parameters were suggestive of anemia, thrombocytopenia, acute kidney injury, coagulopathy, and hepatopathy because of which instead of splenectomy, splenic artery embolization with ultrasound-guided splenic hemorrhage drainage was performed for his management as his clinical condition deteriorated. This case report sensitizes newer modalities of treatment of subcapsular splenic hematoma with splenic arterial embolization.
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Affiliation(s)
- Sameera S Dronamraju
- Department of Medicine, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
| | - Shilpa Abhay Gaidhane
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
| | - Khatib Nazli Mahalaqqa
- Department of Evidence Synthesis, School of Epidemiology and Public Health, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
| | - Abhay M Gaidhane
- Department of Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
| | - Amol G Andhale
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
| | - Zahiruddin Syed Quazi
- Department of Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
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16
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Stravitz RT, Fontana RJ, Meinzer C, Durkalski V, Hanje AJ, Olson J, Koch D, Hamid B, Schilsky ML, McGuire B, Ganger D, Liou I, Karvellas CJ, Rule JA, Lisman T, Clasen K, Reuben A, Cripps MW, Lee WM, ALF Study Group. Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure. Hepatology 2021; 74:937-949. [PMID: 33636020 PMCID: PMC10668528 DOI: 10.1002/hep.31767] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 02/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. APPROACH AND RESULTS A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. CONCLUSIONS In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.
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Affiliation(s)
- RT Stravitz
- Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA
| | - RJ Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - C Meinzer
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - V Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - AJ Hanje
- Department of Medicine, The Ohio State University, Columbus, OH
| | - J Olson
- Division of Gastroenterology, University of Kansas Medical Center, Kansas City, KS
| | - D Koch
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - B Hamid
- Department of Medicine, University of California at San Francisco, San Francisco, CA
| | - ML Schilsky
- Divisions of Digestive Disease and Transplant and Immunology, Yale University, New Haven, CT
| | - B McGuire
- Division of Gastroenterology, University of Alabama, Birmingham, AL
| | - D Ganger
- Division of Gastroenterology, Northwestern University, Chicago, IL
| | - I Liou
- Department of Medicine, University of Washington, Seattle, WA
| | - CJ Karvellas
- Division of Gastroenterology (Liver Unit) and Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada
| | - JA Rule
- Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX
| | - T Lisman
- Department of Surgery, University of Groningen, Groningen, The Netherlands
| | - K Clasen
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - A Reuben
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - MW Cripps
- Department of Surgery, University of Texas, Southwestern Medical Center, Dallas, TX
| | - WM Lee
- Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX
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17
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Campello E, Zanetto A, Radu CM, Bulato C, Truma A, Spiezia L, Senzolo M, Garcia-Tsao G, Simioni P. Acute kidney injury is associated with increased levels of circulating microvesicles in patients with decompensated cirrhosis. Dig Liver Dis 2021; 53:879-888. [PMID: 33431230 PMCID: PMC11090178 DOI: 10.1016/j.dld.2020.12.118] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. AIM To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). METHODS We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. RESULTS Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8-10.7]), MELD (OR 1.13 [95%CI 1.02-1.27]), any bleeding (OR 9.07 [95%CI 2.02-40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02-1.07]) were independently associated with 30-day mortality. CONCLUSION AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.
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Affiliation(s)
- Elena Campello
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Alberto Zanetto
- Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, CT, USA; VA-Connecticut Healthcare System, West Haven, CT, USA; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Claudia M Radu
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Cristiana Bulato
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Addolorata Truma
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Luca Spiezia
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Guadalupe Garcia-Tsao
- Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, CT, USA; VA-Connecticut Healthcare System, West Haven, CT, USA
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy.
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18
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Groeneveld DJ, Poole LG, Luyendyk JP. Targeting von Willebrand factor in liver diseases: A novel therapeutic strategy? J Thromb Haemost 2021; 19:1390-1408. [PMID: 33774926 PMCID: PMC8582603 DOI: 10.1111/jth.15312] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/08/2021] [Accepted: 03/22/2021] [Indexed: 12/11/2022]
Abstract
Acute and chronic liver disease are associated with substantial alterations in the hemostatic system. Evidence from both experimental and clinical studies suggests that anticoagulants slow the progression of liver disease. Efficacy of those anticoagulant drugs is, in part, attributed to a reduction of microthrombi formation within the liver. Although anticoagulant drugs show promising results, bleeding risk associated with these drugs is an obvious drawback, particularly in patients with a complex coagulopathy driven by decreased liver function. Identifying therapies that reduce intrahepatic thrombosis with minimal bleeding risk would significantly advance the field. Among the hemostatic alterations observed in patients are substantially increased levels of the platelet-adhesive protein von Willebrand factor (VWF). In contrast, levels of A Disintegrin and Metalloproteinase with Thrombospondin motifs, the enzyme that regulates VWF activity, are significantly reduced in patients with liver disease. Highly elevated VWF levels are proposed to accelerate intrahepatic thrombus formation and thus be a driver of disease progression. Strong clinical evidence suggesting a link between liver disease and changes in VWF is now being matched by emerging mechanistic data showing a detrimental role for VWF in the progression of liver disease. This review focuses on clinical and experimental evidence supporting a connection between VWF function and the progression of acute and chronic liver diseases. Furthermore, with the recent anticipated approval of several novel therapies targeting VWF, we discuss potential strategies and benefits of targeting VWF as an innovative therapy for patients with liver disease.
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Affiliation(s)
- Dafna J Groeneveld
- Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USA
| | - Lauren G Poole
- Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USA
| | - James P Luyendyk
- Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USA
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA
- Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, USA
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19
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Zanetto A, Rinder HM, Campello E, Saggiorato G, Deng Y, Ciarleglio M, Wilson FP, Senzolo M, Gavasso S, Bulato C, Simioni P, Garcia-Tsao G. Acute Kidney Injury in Decompensated Cirrhosis Is Associated With Both Hypo-coagulable and Hyper-coagulable Features. Hepatology 2020; 72:1327-1340. [PMID: 32614088 PMCID: PMC8672302 DOI: 10.1002/hep.31443] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 05/29/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Recent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI. APPROACH AND RESULTS Primary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8 mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n = 23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated. CONCLUSIONS In patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis.
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Affiliation(s)
- Alberto Zanetto
- Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, CT,VA-Connecticut Healthcare System, West Haven, CT,Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Henry M. Rinder
- Laboratory Medicine, Yale School of Medicine, New Haven, CT,Hematology, Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Elena Campello
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Graziella Saggiorato
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Yanhong Deng
- Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT
| | - Maria Ciarleglio
- Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT
| | - Francis P. Wilson
- Program of Applied Translational Research, Yale School of Medicine, New Haven, CT
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Sabrina Gavasso
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Cristiana Bulato
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy
| | - Guadalupe Garcia-Tsao
- Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, CT,VA-Connecticut Healthcare System, West Haven, CT
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20
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Sokou R, Piovani D, Konstantinidi A, Tsantes AG, Parastatidou S, Lampridou M, Ioakeimidis G, Gounaris A, Iacovidou N, Kriebardis AG, Politou M, Kopterides P, Bonovas S, Tsantes AE. A Risk Score for Predicting the Incidence of Hemorrhage in Critically Ill Neonates: Development and Validation Study. Thromb Haemost 2020; 121:131-139. [PMID: 32838471 DOI: 10.1055/s-0040-1715832] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The aim of the study was to develop and validate a prediction model for hemorrhage in critically ill neonates which combines rotational thromboelastometry (ROTEM) parameters and clinical variables. This cohort study included 332 consecutive full-term and preterm critically ill neonates. We performed ROTEM and used the neonatal bleeding assessment tool (NeoBAT) to record bleeding events. We fitted double selection least absolute shrinkage and selection operator logit regression to build our prediction model. Bleeding within 24 hours of the ROTEM testing was the outcome variable, while patient characteristics, biochemical, hematological, and thromboelastometry parameters were the candidate predictors of bleeding. We used both cross-validation and bootstrap as internal validation techniques. Then, we built a prognostic index of bleeding by converting the coefficients from the final multivariable model of relevant prognostic variables into a risk score. A receiver operating characteristic analysis was used to calculate the area under curve (AUC) of our prediction index. EXTEM A10 and LI60, platelet counts, and creatinine levels were identified as the most robust predictors of bleeding and included them into a Neonatal Bleeding Risk (NeoBRis) index. The NeoBRis index demonstrated excellent model performance with an AUC of 0.908 (95% confidence interval [CI]: 0.870-0.946). Calibration plot displayed optimal calibration and discrimination of the index, while bootstrap resampling ensured internal validity by showing an AUC of 0.907 (95% CI: 0.868-0.947). We developed and internally validated an easy-to-apply prediction model of hemorrhage in critically ill neonates. After external validation, this model will enable clinicians to quantify the 24-hour bleeding risk.
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Affiliation(s)
- Rozeta Sokou
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikea, Piraeus, Greece
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | | | - Andreas G Tsantes
- Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Stavroula Parastatidou
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikea, Piraeus, Greece
| | - Maria Lampridou
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikea, Piraeus, Greece
| | - Georgios Ioakeimidis
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikea, Piraeus, Greece
| | - Antonis Gounaris
- Neonatal Intensive Care Unit, University Hospital of Larissa, Larissa, Greece
| | - Nicoletta Iacovidou
- Neonatal Department, Aretaeio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasios G Kriebardis
- Department of Biomedical Science, Laboratory of Reliability and Quality Control in Laboratory Hematology, School of Health and Caring Science, University of West Attica, Egaleo, Greece
| | - Marianna Politou
- Department of Blood Transfusion, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Petros Kopterides
- Intensive Care Unit, Excela Health Westmoreland Hospital, Greensburg, Pennsylvania, United States
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - Argirios E Tsantes
- Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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21
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Warrillow S, Fisher C, Tibballs H, Bailey M, McArthur C, Lawson-Smith P, Prasad B, Anstey M, Venkatesh B, Dashwood G, Walsham J, Holt A, Wiersema U, Gattas D, Zoeller M, Garcia Alvarez M, Bellomo R. Coagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand. J Gastroenterol Hepatol 2020; 35:846-854. [PMID: 31689724 DOI: 10.1111/jgh.14876] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 09/19/2019] [Accepted: 09/21/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). METHODS Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. RESULTS We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41-122) × 109 /L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. CONCLUSION In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies.
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Affiliation(s)
- Stephen Warrillow
- Department of Intensive Care, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine and Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Caleb Fisher
- Department of Intensive Care, Austin Health, Melbourne, Victoria, Australia
| | - Heath Tibballs
- Department of Intensive Care, Austin Health, Melbourne, Victoria, Australia
| | - Michael Bailey
- Department of Medicine and Surgery, The University of Melbourne, Melbourne, Victoria, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University School of Public Health and Preventive Medicine, Victoria, Melbourne, Australia
| | - Colin McArthur
- Medical Research Institute of New Zealand, Auckland, New Zealand
- Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand
| | - Pia Lawson-Smith
- Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand
| | | | - Matthew Anstey
- Department of Intensive Care, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Bala Venkatesh
- Department of Intensive Care, Princess Alexandra Hospital, Brisbane, Australia
| | - Gemma Dashwood
- Department of Intensive Care, Princess Alexandra Hospital, Brisbane, Australia
| | - James Walsham
- Department of Intensive Care, Princess Alexandra Hospital, Brisbane, Australia
| | - Andrew Holt
- Department of Intensive Care, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Ubbo Wiersema
- Department of Intensive Care, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - David Gattas
- Department of Intensive Care, Royal Prince Alfred Hospital, Sydney, Australia
| | - Matthew Zoeller
- Department of Intensive Care, Royal Prince Alfred Hospital, Sydney, Australia
| | - Mercedes Garcia Alvarez
- Department of Anesthesiology and Pain Medicine, Hospital Santa Creu i Sant Pau, University of Barcelona, Barcelona, Spain
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine and Surgery, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia
- Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital and University of Melbourne, Melbourne, Australia
- Centre for Integrated Critical Care, The University of Melbourne, Melbourne, Australia
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22
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de Ávila RE, José Fernandes H, Barbosa GM, Araújo AL, Gomes TCC, Barros TG, Moreira RLF, Silva GLC, de Oliveira NR. Clinical profiles and factors associated with mortality in adults with yellow fever admitted to an intensive care unit in Minas Gerais, Brazil. Int J Infect Dis 2020; 93:90-97. [PMID: 32004691 DOI: 10.1016/j.ijid.2020.01.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/17/2020] [Accepted: 01/18/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Yellow fever (YF) is a viral hemorrhagic disease caused by an arbovirus from the Flaviviridae family. Data on the clinical profile of severe YF in intensive care units (ICUs) are scarce. This study aimed to evaluate factors associated with YF mortality in patients admitted to a Brazilian ICU during the YF outbreaks of 2017 and 2018. METHODS This was a longitudinal cohort case series study that included YF patients admitted to the ICU. Demographics, clinical and laboratory data were analyzed. Cox regression identified independent predictors of death risk. RESULTS A total of 114 patients were studied. The median age was 48 years, and 92.1% were males. In univariate analysis, jaundice, leukopenia, bradycardia, prothrombin time, expressed as a ratio to the international normalized ratio-(PT-INR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, lactate, arterial pH and bicarbonate, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score 3 (SAPS 3) severity scores, transfusion of fresh frozen plasma, acute renal failure (Acute Kidney Injury Network stage III (AKIN III)), hemodialysis, cumulative fluid balance at 72 h of ICU, vasopressor use, seizures and grade IV encephalopathy were significantly associated with mortality. In multivariate analysis, factors independently associated with YF mortality were PT-INR, APACHE II, and grade IV hepatic encephalopathy. CONCLUSIONS In the large outbreak in Brazil, factors independently associated with death risk in YF were: PT-INR, APACHE II, and grade IV hepatic encephalopathy. Early identification of patients with YF mortality risk factors may be very useful. Once these patients with a poor prognosis have been identified, proper management should be promptly implemented.
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Affiliation(s)
- Renata Eliane de Ávila
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil.
| | - Herbert José Fernandes
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil.
| | - Gerdson Magno Barbosa
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil
| | - Argus Leão Araújo
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil
| | | | - Teresa Gamarano Barros
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil
| | - Ricardo Luiz Fontes Moreira
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil
| | - Guilherme Lima Castro Silva
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil
| | - Neimy Ramos de Oliveira
- Hospital Eduardo de Menezes (HEM), Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Brazil
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23
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Griffin BR, Kohtz PD, Bronsert M, Reece TB, Cleveland JC, Fullerton DA, Faubel S, Aftab M. Postoperative Complications Are Not Elevated in Well-Compensated ESRD Patients Undergoing Cardiac Surgery: End-Stage Renal Disease Cardiac Surgery Outcomes. J Surg Res 2019; 247:136-143. [PMID: 31785887 DOI: 10.1016/j.jss.2019.10.032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 10/02/2019] [Accepted: 10/22/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Patients with end-stage renal disease (ESRD) are at high risk for cardiac disease requiring surgery, and have been shown to have increased surgical risks. There have been significant improvements in ESRD management, surgical techniques, and patient selection over the past 10 y. We evaluated rates of serious postoperative outcomes in stable, well-dialyzed patients with ESRD undergoing nonemergent cardiac surgery compared to the general cardiac surgery population. METHODS In this propensity-score matched study, we evaluated 1451 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital (UCH) between 2011 and 2016. Patients with ESRD were compared to nonESRD patients. The primary outcome was a composite endpoint, including 30-d mortality, stroke, postoperative infection, and prolonged intensive care unit (ICU) length of stay (LOS). RESULTS A total of 35 patients with ESRD met inclusion criteria. These select patients were younger with few comorbidities than the nonESRD population. There were no statistically significant differences in the composite outcome between ESRD and nonESRD patients in the propensity-matched analysis (OR 0.70, CI 0.29-1.72, P = 0.44). There were no significant differences or trends for in-hospital mortality, postoperative stroke, infection, ICU LOS, or hospital LOS between the patients with and without ESRD. CONCLUSIONS Stable ESRD patients undergoing nonemergent surgery are not at increased risk of major postoperative complications when compared to those without ESRD. Well-compensated ESRD patients should not be excluded from surgical consideration.
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Affiliation(s)
- Benjamin R Griffin
- Division of Nephrology, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Patrick D Kohtz
- Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Michael Bronsert
- Adult and Child Consortium for Health Outcomes Research and Delivery Science and Surgical Outcomes and Applied Research, University of Colorado, Aurora, Colorado
| | - T Brett Reece
- Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Joseph C Cleveland
- Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - David A Fullerton
- Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Sarah Faubel
- Division of Nephrology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Muhammad Aftab
- Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado.
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24
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Spontaneous renal hemorrhage: critical analysis of different lines of management in non-traumatic patients: a single tertiary center experience. Int Urol Nephrol 2019; 52:423-429. [PMID: 31686280 DOI: 10.1007/s11255-019-02333-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 10/30/2019] [Indexed: 10/25/2022]
Abstract
PURPOSE To assess clinical presentation and outcomes of different treatment strategies in cases of spontaneous renal hemorrhage (SRH). METHODS A retrospective analysis of patients with SRH between 2000 and 2018 was performed. Patients' demographics, clinical presentation, laboratory and radiological investigations, and different lines of treatment were retrieved. The primary outcome was to assess the predictors of the success of conservative treatment. The secondary outcome was to assess the long-term renal function outcome comparing serum creatinine, e GFF, and CT-assessed renal volume at last follow-up with baseline values. RESULTS The study included 42 (23 males and 19 women) patients with mean ± SD age was 48.1 ± 17.8 years. Conservative management was successful in 19 (46%) patients. Trans-arterial embolization (TAE) was performed in 13 patients (30%) to control active bleeding. Ten patients (25%) required surgical exploration and nephrectomy. Lower serum creatinine (P = 0.003), higher prothrombin concentration (P = 0.04), lower hematoma size (P = 0.02), and non-AML lesions (P = 0.03) were independent predictors of conservative management success. Unlike the TAE-treated group, serum creatinine increased significantly (P = 0.04) with a significant decrease in e-GFR (P = 0.02) and renal volume (P < 0.001) of affected kidneys at last follow-up after conservative treatment. CONCLUSION Although SRH is a life-threatening condition, conservative treatment is successful in a certain subset of patients. However, it is associated with significant deterioration of the affected kidney function as well as renal volume.
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25
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Acute kidney injury is associated with low factor XIII in decompensated cirrhosis. Dig Liver Dis 2019; 51:1409-1415. [PMID: 30967339 DOI: 10.1016/j.dld.2019.03.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 03/08/2019] [Accepted: 03/13/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS The coagulation system is known to be rebalanced but fragile in stable cirrhosis. Acute kidney injury (AKI) is common in these patients and associated with an increased bleeding risk. We aimed to assess coagulation parameters in this population. METHODS We prospectively enrolled 43 hospitalized patients with decompensated cirrhosis with (n = 22) or without (n = 21) AKI. Coagulation factor levels, viscoelastic coagulation assay, and thrombin generation assay were performed and compared between these groups and a healthy reference group. RESULTS Conventional markers of coagulation were not statistically different between patients with and without AKI. Factor XIII was significantly reduced in all patients with cirrhosis compared to healthy controls (p = <0.0001). In patients with AKI, factor XIII was significantly lower compared to patients without AKI (AKI 38% vs. non-AKI 60% p = 0.002). In patients with cirrhosis, factor XIII had a significantly positive correlation with EXTEM maximal clot firmness (r = 0.5440, p = 0.0002) and FIBTEM maximal clot firmness (r = 0.7397, p = <0.0001) and a negative correlation with EXTEM clot formation time (-0.413, p = 0.0065). CONCLUSIONS Factor XIII was significantly reduced in decompensated cirrhosis patients with AKI compared to decompensated patients without AKI. These findings suggest that exacerbation of factor XIII deficiency in AKI in decompensated cirrhosis may affect bleeding risk and warrants further study.
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26
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Northup P, Reutemann B. Management of Coagulation and Anticoagulation in Liver Transplantation Candidates. Liver Transpl 2018; 24:1119-1132. [PMID: 30142249 DOI: 10.1002/lt.25198] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 08/22/2016] [Accepted: 10/31/2016] [Indexed: 02/07/2023]
Abstract
Hemostasis is a complex balance of clot formation and dissolution that is largely modulated by protein synthesis and degradation in the liver. In the state of end-stage liver disease, there is a disruption of the hemostatic system due to hepatic protein synthetic dysfunction. Because historical clinical laboratory testing often only analyzes a portion of the hemostasis system, the clinician may be misled into believing that cirrhosis patients are imbalanced with a tendency toward bleeding. The modern understanding of hemostasis in cirrhosis involves a rebalance of hemostasis with a tenuous equilibrium between clotting and bleeding, but an equilibrium nonetheless. The clinician should be aware of this rebalance and not depend on limited and flawed laboratory testing in making judgments about the tendency for bleeding or clotting based on these values alone. Prophylactic protocol transfusions including large doses of fresh frozen plasma to "correct" the international normalized ratio are good examples of ineffective and potentially harmful interventions based on an outdated understanding of hemostasis in cirrhosis. Conversely, a thrombotic state is increasingly recognized in patients with cirrhosis, and conditions such as portal vein thrombosis are now becoming important therapeutic targets in many liver transplantation (LT) candidates and other patients with chronic liver disease. This article will introduce the reader to the modern understanding of hemostasis in cirrhosis, describe the common pitfalls and opportunities in treating hemostasis system abnormalities in the LT candidate particularly in regards to preprocedural prophylactic transfusions, and discuss therapeutic targets and interventions for thrombotic complications in the end-stage liver disease population.
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Affiliation(s)
- Patrick Northup
- Center for the Study of Coagulation in Liver Disease, Division of Gastroenterology and Hepatology, University of Virginia Health System, University of Virginia, Charlottesville, VA
| | - Bethany Reutemann
- Center for the Study of Coagulation in Liver Disease, Division of Gastroenterology and Hepatology, University of Virginia Health System, University of Virginia, Charlottesville, VA
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27
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Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, Lee WM, the Acute Liver Failure Study Group. Bleeding complications in acute liver failure. Hepatology 2018; 67:1931-1942. [PMID: 29194678 PMCID: PMC5906191 DOI: 10.1002/hep.29694] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 09/09/2017] [Accepted: 11/27/2017] [Indexed: 01/09/2023]
Abstract
In patients with acute liver failure (ALF), elevated prothrombin time and thrombocytopenia can fuel a perception of a bleeding tendency. However, the incidence, site, risk factors, and clinical significance of bleeding complications have not been quantified in a large cohort of patients with ALF. We studied 1,770 adult patients enrolled in the ALF Study Group Registry between 1998 and 2016. Bleeding complications and blood component transfusions were collected for 7 days after admission. The relationship of bleeding complications to 21-day mortality was assessed. Despite a median international normalized ratio of 2.7 and platelet count of 96 × 109 /L on admission, bleeding complications were observed in only 187 patients (11%), including 173 spontaneous and 22 postprocedural bleeding episodes. Eighty-four percent of spontaneous bleeding episodes were from an upper gastrointestinal source and rarely resulted in red blood cell transfusion. Twenty patients experienced an intracranial bleed; half of these occurred spontaneously and half after intracranial pressure monitor placement, and this was the proximate cause of death in 20% and 50%, respectively. Bleeders and patients who received red blood cell transfusions were more acutely ill from extrahepatic organ system failure but not from hepatocellular failure. Consistent with this observation, bleeding complications were associated with lower platelet counts but not higher international normalized ratio. Transfusion of any blood component was associated with nearly 2-fold increased death or need for liver transplantation at day 21, but bleeding complications were the proximate cause of death in only 5% of cases. CONCLUSIONS Despite a perceived bleeding diathesis, clinically significant bleeding is uncommon in patients with ALF; bleeding complications in patients with ALF are markers of severe systemic inflammation rather than of coagulopathy and so portend a poor prognosis. (Hepatology 2018;67:1931-1942).
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Affiliation(s)
- R. Todd Stravitz
- Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA
| | - Caitlyn Ellerbe
- Department of Biostatistics, Medical University of South Carolina, Charleston, SC
| | - Valerie Durkalski
- Department of Biostatistics, Medical University of South Carolina, Charleston, SC
| | - Michael Schilsky
- Division of Gastroenterology and Hepatology, Yale University, New Haven, CT
| | | | - Carolyn Peterseim
- Department of Biostatistics, Medical University of South Carolina, Charleston, SC
| | - William M. Lee
- University of Texas-Southwestern Medical Center, Dallas, TX
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28
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Stravitz RT. Hematological Issues in Liver Disease. HEPATIC CRITICAL CARE 2018:163-178. [DOI: 10.1007/978-3-319-66432-3_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Lisman T, Bernal W. Management of Hemostatic Disorders in Patients With Advanced Liver Disease Admitted to an Intensive Care Unit. Transfus Med Rev 2017; 31:245-251. [DOI: 10.1016/j.tmrv.2017.06.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 05/19/2017] [Accepted: 06/20/2017] [Indexed: 02/07/2023]
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30
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Lee KCL, Baker L, Mallett S, Riddell A, Chowdary P, Alibhai H, Chang YM, Priestnall S, Stanzani G, Davies N, Mookerjee R, Jalan R, Agarwal B. Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs. Sci Rep 2017; 7:9347. [PMID: 28839178 PMCID: PMC5571150 DOI: 10.1038/s41598-017-09508-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 07/26/2017] [Indexed: 02/06/2023] Open
Abstract
Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability.
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Affiliation(s)
- Karla Chui Luan Lee
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK. .,Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK.
| | - Luisa Baker
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Susan Mallett
- Department of Anaesthesia, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Anne Riddell
- Katherine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Pratima Chowdary
- Katherine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Hatim Alibhai
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Yu-Mei Chang
- Department of Research Support, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Simon Priestnall
- Department of Pathobiology and Population Sciences, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Giacomo Stanzani
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Nathan Davies
- Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
| | - Rajeshwar Mookerjee
- Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
| | - Rajiv Jalan
- Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
| | - Banwari Agarwal
- Department of Intensive Care Medicine, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
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31
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Tangvoraphonkchai K, Riddell A, Davenport A. Platelet activation and clotting cascade activation by dialyzers designed for high volume online hemodiafiltration. Hemodial Int 2017; 22:192-200. [DOI: 10.1111/hdi.12586] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
| | - Anne Riddell
- Haemophilia Centre & Thrombosis Unit; Royal Free Hospital; Pond Street, London NW3 2QG
| | - Andrew Davenport
- UCL Centre for Nephrology; University College London, Royal Free Hospital; London
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Wendon, J, Cordoba J, Dhawan A, Larsen FS, Manns M, Samuel D, Simpson KJ, Yaron I, Bernardi M. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017; 66:1047-1081. [PMID: 28417882 DOI: 10.1016/j.jhep.2016.12.003] [Citation(s) in RCA: 602] [Impact Index Per Article: 75.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 12/07/2016] [Indexed: 02/06/2023]
Abstract
The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention. These, as well as additional clinical procedures will be the subject of these clinical practice guidelines.
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Huang MJ, Wei RB, Su TY, Wang Y, Li QP, Yang X, Lv XM, Chen XM. Impact of acute kidney injury on coagulation in adult minimal change nephropathy. Medicine (Baltimore) 2016; 95:e5366. [PMID: 27861367 PMCID: PMC5120924 DOI: 10.1097/md.0000000000005366] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A hypercoagulable state exists in patients with nephrotic syndrome (NS), which more easily leads to venous thromboembolism (VTE). However, whether acute kidney injury (AKI), a common complication of NS, affects the hypercoagulable state and VTE has rarely been elucidated. In this study, we aimed to explore coagulation changes and analyze relevant influencing factors in NS-AKI patients.A total of 269 consecutive NS patients with minimal change disease (MCD) between 2011 and 2016 were included in this observational study. Ninety-one cases were in the AKI group and 178 cases in the non-AKI group. The 1:1 propensity score matching (PSM) method was applied to match the baseline information. The coagulation biomarkers were compared, and the thrombosis events were recorded. Linear correlation was performed to detect any relation between D-dimer and clinical data.The PSM method gave matched pairs of 88 MCD patients with AKI and non-AKI patients, resulting in no differences in baseline information. The D-dimer, fibrinogen, and thromboelastography parameters maximum amplitude (MA), G values of the MCD-AKI patients were significantly higher than the levels of the MCD patients without AKI (D-dimer: 1.8 [1.0, 3.3] vs 1.1 [0.6, 1.7] mg/L, P < 0.001; fibrinogen: 7.0±2.0 vs 6.5 ± 1.4 g/L, P = 0.036; MA: 74.6 ± 5.0 vs 70.5 ± 5.3 mm, P = 0.020; G: 15.7 ± 5.3 vs 12.5 ± 3.3, P = 0.034). For the MCD patients, the serum creatinine, white blood cell count, and interleukin-6 levels in the patients with D-dimers >1 mg/L were significantly higher than those of patients with D-dimers ≤1 mg/L. The correlation analysis showed that the D-dimer level was correlated with serum creatinine, white blood cell count, and interleukin-6 (r = 0.410, P = < 0.001; r = 0.248, P = < 0.001; r = 0.306, P = < 0.001, respectively). Five deep vein thrombosis events occurred in the AKI group and 1 pulmonary embolism event occurred in the non-AKI group after adjusting the propensity score value. AKI appeared to have an association with higher incidence of VTE, but the difference was not statistically significant (RR: 4.9, 95% CI: 0.6-42.7, P = 0.154).The MCD-NS patients complicated with AKI had a more severe hypercoagulable state, which might be associated with the active inflammation of AKI that mediated activation of the coagulation system.
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Magnusson M, Ignjatovic V, Hardikar W, Monagle P. A conceptual and practical approach to haemostasis in paediatric liver disease. Arch Dis Child 2016; 101:854-9. [PMID: 27013527 DOI: 10.1136/archdischild-2015-309535] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2015] [Accepted: 03/02/2016] [Indexed: 12/15/2022]
Abstract
UNLABELLED Children with liver disease can develop severe bleeding episodes and thrombosis. Liver failure usually results in decreased levels of procoagulant and anticoagulant factors. Additional risk factors, including changes in vascular flow and endothelial function, are of importance for the development of bleeding or thrombosis in individual vascular beds. Detailed studies of haemostatic disturbances in the setting of paediatric liver disease are sparse and extrapolation from adult studies is common. The spectrum of liver diseases and the haemostatic system differs between children and adults. Specific paediatric liver diseases are reported to have more distinctive effects on haemostasis and the risk of bleeding and/or thrombosis. CONCLUSION we propose a model regarding haemostasis in paediatric liver disease, taking into account a number of specific variables and mechanisms, as well as the type of liver disease, which will provide a framework for clinical decision-making in these complex patients.
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Affiliation(s)
- Maria Magnusson
- CLINTEC, Division of Pediatrics, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden MMK, Clinical Chemistry and Blood Coagulation Research, Karolinska Institutet, Stockholm, Sweden Department of Paediatrics, University of Melbourne, Melbourne, Australia Haematology Research, Murdoch Childrens Research Institute, Melbourne, Australia
| | - Vera Ignjatovic
- Department of Paediatrics, University of Melbourne, Melbourne, Australia Haematology Research, Murdoch Childrens Research Institute, Melbourne, Australia
| | - Winita Hardikar
- Department of Paediatrics, University of Melbourne, Melbourne, Australia Department of Gastroenterology, Royal Children's Hospital, Melbourne, Australia
| | - Paul Monagle
- Department of Paediatrics, University of Melbourne, Melbourne, Australia Haematology Research, Murdoch Childrens Research Institute, Melbourne, Australia Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia
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Valerio C, Theocharidou E, Davenport A, Agarwal B. Human albumin solution for patients with cirrhosis and acute on chronic liver failure: Beyond simple volume expansion. World J Hepatol 2016; 8:345-354. [PMID: 26981172 PMCID: PMC4779163 DOI: 10.4254/wjh.v8.i7.345] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 12/22/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
To provide an overview of the properties of human serum albumin (HSA), and to review the evidence for the use of human albumin solution (HAS) in critical illness, sepsis and cirrhosis. A MEDLINE search was performed using the terms “human albumin”, “critical illness”, “sepsis” and “cirrhosis”. The references of retrieved articles were reviewed manually. Studies published between 1980 and 2014 were selected based on quality criteria. Data extraction was performed by all authors. HSA is the main plasma protein contributing greatly to its oncotic pressure. HSA demonstrates important binding properties for endogenous and exogenous toxins, drugs and drug metabolites that account for its anti-oxidant and anti-inflammatory properties. In disease states, hypoalbuminaemia is secondary to decreased HSA production, increased loss or transcapillary leakage into the interstitial space. HSA function can be also altered in disease with reduced albumin binding capacity and increased production of modified isoforms. HAS has been used as volume expander in critical illness, but received criticism due to cost and concerns regarding safety. More recent studies confirmed the safety of HAS, but failed to show any survival benefit compared to the cheaper crystalloid fluids, therefore limiting its use. On the contrary, in cirrhosis there is robust data to support the efficacy of HAS for the prevention of circulatory dysfunction post-large volume paracentesis and in the context of spontaneous bacterial peritonitis, and for the treatment of hepato-renal syndrome and hypervolaemic hyponatraemia. It is likely that not only the oncotic properties of HAS are beneficial in cirrhosis, but also its functional properties, as HAS replaces the dysfunctional HSA. The role of HAS as the resuscitation fluid of choice in critically ill patients with cirrhosis, beyond the established indications for HAS use, should be addressed in future studies.
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Aron J, Agarwal B, Davenport A. Extracorporeal support for patients with acute and acute on chronic liver failure. Expert Rev Med Devices 2016; 13:367-80. [PMID: 26894968 DOI: 10.1586/17434440.2016.1154455] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds.
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Affiliation(s)
- Jonathan Aron
- a King's College Hospital , London , United Kingdom of Great Britain and Northern Ireland
| | - Banwari Agarwal
- b Intensive Care Unit , Royal Free Hospital , London , United Kingdom of Great Britain and Northern Ireland
| | - Andrew Davenport
- c UCL Centre for Nephrology , Royal free Hospital , London , United Kingdom of Great Britain and Northern Ireland
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Minimizing risks associated with renal replacement therapy in patients with Ebola virus disease. Kidney Int 2016; 87:5-7. [PMID: 25469847 DOI: 10.1038/ki.2014.375] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Davenport A. Early start renal replacement therapy for acute kidney injury-Universal panacea or another case of over medicalization? Hemodial Int 2015; 19 Suppl 3:S34-9. [DOI: 10.1111/hdi.12351] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Andrew Davenport
- UCL Center for Nephrology; Royal Free Hospital; University College London Medical School; London UK
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Davenport A. Portable and wearable dialysis devices for the treatment of patients with end-stage kidney failure: Wishful thinking or just over the horizon? Pediatr Nephrol 2015; 30:2053-60. [PMID: 25330876 PMCID: PMC4623087 DOI: 10.1007/s00467-014-2968-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 09/03/2014] [Accepted: 09/16/2014] [Indexed: 11/30/2022]
Abstract
Dialysis is a life-sustaining treatment for patients with end-stage kidney disease. In a different context, for many patients this treatment is the focal point around which their life revolves, not only due to the time spent travelling to and from treatment sessions and the time dedicated to the dialysis treatment itself, but also due to the accompanying dietary and fluid restrictions and medication burden. Wearable and portable dialysis devices could potentially improve patient quality of life by allowing patients to continue with their daily activities of life while undergoing dialysis, as well as by loosening-or removing entirely-dietary and fluid restrictions and reducing pill burden. Advances in nanotechnology manufacturing coupled with advances in electronics and miniaturisation have allowed a new generation of wearable and portable dialysis devices to be developed which are now undergoing large animal and patient clinical trials. We are therefore potentially at a new dawn in the treatment of dialysis patients with the first generation of wearable and portable dialysis devices, which may well revolutionise the treatment and quality of life for patients with end-stage kidney disease.
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Affiliation(s)
- Andrew Davenport
- UCL Centre for Nephrology, Royal Free Hospital, University College London Medical School, Rowland Hill Street, London, NW3 2PF, UK.
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Lemoinne S, Thabut D, Housset C, Moreau R, Valla D, Boulanger CM, Rautou PE. The emerging roles of microvesicles in liver diseases. Nat Rev Gastroenterol Hepatol 2014; 11:350-61. [PMID: 24492276 DOI: 10.1038/nrgastro.2014.7] [Citation(s) in RCA: 133] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Microvesicles (MVs) are extracellular vesicles released by virtually all cells, under both physiological and pathological conditions. They contain lipids, proteins, RNAs and microRNAs and act as vectors of information that regulate the function of target cells. This Review provides an overview of the studies assessing circulating MV levels in patients with liver diseases, together with an insight into the mechanisms that could account for these changes. We also present a detailed analysis of the implication of MVs in key processes of liver diseases. MVs have a dual role in fibrosis as certain types of MVs promote fibrolysis by increasing expression of matrix metalloproteinases, whereas others promote fibrosis by stimulating processes such as angiogenesis. MVs probably enhance portal hypertension by contributing to intrahepatic vasoconstriction, splanchnic vasodilation and angiogenesis. As MVs can modulate vascular permeability, vascular tone and angiogenesis, they might contribute to several complications of cirrhosis including hepatic encephalopathy, hepatopulmonary syndrome and hepatorenal syndrome. Several results also suggest that MVs have a role in hepatocellular carcinoma. Although MVs represent promising biomarkers in patients with liver disease, methods of isolation and subsequent analysis must be standardized.
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Affiliation(s)
- Sara Lemoinne
- INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Sorbonne Universités, Université Pierre et Marie Curie Paris 6, 27 Rue Chaligny, 75571 Paris, France
| | - Dominique Thabut
- INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Sorbonne Universités, Université Pierre et Marie Curie Paris 6, 27 Rue Chaligny, 75571 Paris, France
| | - Chantal Housset
- INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Sorbonne Universités, Université Pierre et Marie Curie Paris 6, 27 Rue Chaligny, 75571 Paris, France
| | - Richard Moreau
- INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Université Paris-Diderot-Paris 7, Hôpital Bichat, 46 Rue Henri Huchard, 75018 Paris, France
| | - Dominique Valla
- Service d'hépatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92100 Clichy, France
| | - Chantal M Boulanger
- INSERM, U970, Paris Cardiovascular Research Center, Paris, Université Paris Descartes, Sorbonne Paris Cité, 56 Rue Leblanc, 75015 Paris, France
| | - Pierre-Emmanuel Rautou
- INSERM, U970, Paris Cardiovascular Research Center, Paris, Université Paris Descartes, Sorbonne Paris Cité, 56 Rue Leblanc, 75015 Paris, France
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Clevenger B, Mallett SV. Transfusion and coagulation management in liver transplantation. World J Gastroenterol 2014; 20:6146-6158. [PMID: 24876736 PMCID: PMC4033453 DOI: 10.3748/wjg.v20.i20.6146] [Citation(s) in RCA: 121] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 02/10/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation.
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Girardis M, Marietta M. Hemostasis in acute liver and kidney failure: nothing is as it seems. Kidney Int 2013; 84:22-4. [PMID: 23812363 DOI: 10.1038/ki.2013.121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Very little is known about the behavior of the hemostatic system in patients with acute kidney injury (AKI) associated with acute liver failure (ALF). Agarwal and colleagues show that patients who suffer from both ALF and AKI exhibit a higher degree of hemostasis impairment than those with normal renal function. Both anticoagulant and procoagulant factors were impaired. The development of AKI appears to displace the hemostatic equilibrium toward a more prothrombotic pattern.
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Affiliation(s)
- Massimo Girardis
- Intensive Care Unit, Department of Anaesthesiology and Intensive Care, University Hospital of Modena, Modena, Italy.
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