Cirrhosis is associated with a procoagulant state that may worsen disease evolution. Anticoagulation could be of particular interest in these patients. However, evidence on the use of direct oral anticoagulants (DOAC) in patients with cirrhosis is limited.

Our aim was to explore the in vitro effect of DOAC on thrombin generation (TG) in plasma from patients with cirrhosis compared to plasma from healthy controls.

Platelet-poor-plasma was obtained from patients with cirrhosis (n = 87; Child-Turcotte-Pugh class: A, n = 68; B, n = 14; C, n = 5) and controls (n = 17). TG was assessed with ST-Genesia analyzer. Plasma from patients with cirrhosis and thrombomodulin-mediated inhibition of endogenous thrombin potential <20% (ThromboScreen) were defined as "highly procoagulant" (n = 36), ≥20% to 50% as "procoagulant" (n = 31), and >50% as "nonprocoagulant" (n = 20). Plasma samples were spiked with apixaban, edoxaban, rivaroxaban, or dabigatran at final concentrations of 50 and 150 ng/mL. TG was measured (DrugScreen) in plasma samples without and with DOAC.

Apixaban, edoxaban, and rivaroxaban demonstrated significantly reduced inhibition of in vitro TG parameters in highly procoagulant plasma from patients with cirrhosis compared to plasma from controls, whereas possibly artifactual results were observed with dabigatran.

The anticoagulant potency of DOAC differs according to the individual procoagulant potential. Highly procoagulant plasma from patients with cirrhosis is less sensitive to the anticoagulant action of apixaban, edoxaban, and rivaroxaban than control plasma. These results, if confirmed in vivo, would support the concept of personalizing anticoagulant treatment in patients with a highly procoagulant state.

This research focused on exploring the association between coagulopathy scores and the survival outcomes, both short-term and long-term, in individuals diagnosed with liver cirrhosis complicated by sepsis.

This study retrospectively analyzed data from individuals with liver cirrhosis and sepsis who were admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center between 2008 and 2022. The main outcome of interest was all-cause mortality within 28 days post-admission, while the secondary outcome assessed mortality within 90 days. We used the Kaplan-Meier analysis to compare the mortality risk among the different groups. To evaluate the relationship between coagulopathy score and mortality risk in patients with liver cirrhosis and sepsis, a multivariate Cox proportional hazards regression analysis was performed. The predictive performance of the coagulopathy score for short- and long-term all-cause mortality was assessed using receiver operating characteristic (ROC) curve analysis, which included evaluation of its sensitivity, specificity, and area under the curve. Subgroup analyses were performed to evaluate the relationship between coagulopathy score and survival across different groups.

The study included a total of 2,278 patients. Kaplan-Meier survival analysis demonstrated that individuals with elevated coagulopathy scores exhibited markedly higher rates of ICU mortality, in-hospital mortality, as well as 28-day and 90-day mortality, with all log-rank tests yielding P-values of less than 0.001. The results of the multivariate Cox regression analysis showed that an elevated coagulopathy score was independently linked to higher 28-day and 90-day all-cause mortality, both before and after controlling for potential confounders. ROC curve analysis showed that although the coagulopathy score was slightly less predictive of prognosis than the Model for End-stage Liver Disease score, it significantly outperformed the Sequential Organ Failure Assessment score and the Sepsis-induced Coagulopathy score. Subgroup analysis revealed no significant interaction between the coagulopathy score and survival across the different subgroups.

Higher coagulopathy scores in critically ill patients with liver cirrhosis and sepsis were independently associated with poor prognosis. Due to its simplicity and potential predictive value, the coagulopathy score can serve as an effective complement to existing clinical tools for managing critically ill patients with liver cirrhosis and sepsis.

Liver cirrhosis and portal hypertension (PHT) can lead to lymphatic abnormalities and coagulation dysfunction. Because lymphangiogenesis may relieve liver cirrhosis and PHT, the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.

To investigate the role of lymphangiogenesis in preclinical PHT models.

Immunohistochemistry and transcriptome sequencing of bile duct ligation (BDL) and control lymphatic samples were conducted to reveal the indicated signaling pathways. Functional enrichment analyses were performed on the differentially expressed genes and hub genes. Adenoviral infection of vascular endothelial growth factor C (VEGF-C), platelet-rich plasma (PRP), and VEGF3 receptor (VEGFR) inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models. Histology, hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.

Lymphangiogenesis was increased in the BDL rat model. Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence, aggregation, and activation. The role of PHT in the rat model was investigated by activating (PRP) and inhibiting (MAZ-51) the lymphatic system. PRP promoted lymphangiogenesis, which increased lymphatic drainage, alleviated portal pressure, reduced liver fibrosis, inhibited inflammation, inhibited angiogenesis, and suppressed mesenteric artery remodeling. MAZ-51 reversed the above improvements.

Via VEGF-C/VEGFR-3, platelets impede fibrosis, angiogenesis, and mesenteric artery remodeling, ultimately alleviating PHT. Thus, platelet intervention is a therapeutic approach for cirrhosis and PHT.

Critically ill patients with liver cirrhosis exhibit complex alterations in coagulation that should be considered in clinical acute management. As routine laboratory tests (e.g., INR, aPTT, platelet count) cannot always adequately reflect the coagulation status of critically ill patients with liver cirrhosis, functional hemostatic tests, such as viscoelastic tests, should also be used to assess coagulation disorders in these patients. If invasive procedures are planned, hemostatic interventions to prevent bleeding and measures to stabilize coagulation disorders should be considered depending on the risk of procedure-associated bleeding, while a prophylactic routine correction of abnormal laboratory coagulation parameters should be avoided. If an acute bleeding complication manifests in critically ill patients with liver cirrhosis, an individualized correction of hemostatic changes is indicated in addition to prompt identification of the source of bleeding. This review article describes the pathophysiological changes underlying the altered hemostatic system in critically ill patients with liver cirrhosis and provides an overview of diagnostic and therapeutic options for hemostatic complications.

Cerebral arteriovenous malformations (AVMs) have historically been considered congenital lesions with treatment options including surgery, radiation therapy, and observation. Spontaneous resolution of cerebral AVMs remains an exceedingly rare event with poorly understood pathophysiology.

Herein we report a retrospective case review of a 28-year-old man with alcoholic cirrhosis who presented with a seizure 3 weeks after liver transplantation. Neuroimaging confirmed the presence of a Spetzler-Martin grade 2 AVM in the right frontal lobe. Due to the recent liver transplantation, treatment was deferred at the time of initial diagnosis and the patient was observed for a course of 1 year. Follow-up imaging 1 year later showed resolution of the AVM, confirmed by a catheter angiogram.

Spontaneous resolution of cerebral AVMs is a rare event. Treatment of chronic liver disease resulted in the normalization of angiogenic factors that likely led to AVM resolution. This case provides valuable insight into the vital role of angiogenesis in the natural history of AVMs.

In clinical practice, the d-dimer levels rule out venous thromboembolism and diagnose disseminated intravascular coagulation. d-dimers increase in both physiological and pathological conditions. Liver cirrhosis, especially in the final stages, is characterized by complex coagulation and fibrinolysis factor disorders. Multiple mechanisms tried to explain the increased d-dimer levels in patients with liver cirrhosis and ascites. The d-dimer cut-off level used to rule out venous thromboembolism in cirrhosis is higher than that used to confirm the diagnosis of VTE or DIC in noncirrhotic patients. The cut-off d-dimer level used for the prognosis of thrombotic events is not standardized in advanced liver cirrhosis. Thus, it is necessary to update the clinical guidelines regarding the usefulness of d-dimer testing in advanced liver cirrhosis and the cut-off d-dimer levels, which should vary based on the detection method.

Patients with malignant tumors are prone to present hypercoagulability of blood and form thrombosis, and its pathogenesis is complex involving various factors from clinical and histopathological to genetic influences. Current studies on the potential mechanism of blood hypercoagulability in patients with malignant tumors focus on the following aspects but are not limited: (1) tumor cells release coagulant-promoting substances, (2) tumor cells interact with the fibrinolytic system, (3) tumor cell-mediated platelet activation, (4) tumor-associated complement activation, and (5) genetic factors and clinical factors. Especially, the pathogenesis of blood hypercoagulability is in-depth analyzed covering tumor cells' release of procoagulant substances, the interplay of cancer cells and fibrinolytic system, platelet activation mediated by cancer cells, cancer-associated complement activation, and the action of genetic and clinical factors. We review the pathogenesis of blood hypercoagulability in patients with malignant tumors, which will assist in the research and development of new drugs and providing theoretical support for the formulation of the best treatment plan for patients, to prolong the survival of patients.

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

To date, there is an ongoing debate regarding the ability to predict PVT development using markers of FVIII or FVIII/PC ratio. This study presents evidence-based medical findings on the influence of FVIII activity levels and FVIII/PC values in the formation of PVT in cirrhosis.

The search for original studies on risk factors for portal vein thrombosis (PVT) associated with cirrhosis was conducted, which primarily focused on comparing circulating FVIII activity levels or FVIII/PC ratio in cirrhotic patients with and without PVT. The quality of evidence from each study was assessed using the Newcastle-Ottawa Scale.

The meta-analysis included a total of 10 original studies. In total, 2250 cirrhotic patients were included, with 414 having PVT and 1836 without PVT. The pooled analysis using a random-effects model showed no significant difference in standardized mean difference (SMD) for FVIII activity levels in cirrhotic patients with or without PVT (SMD = 0.12, 95% CI=-0.46 to 0.70, P = 0.68), but there was significant heterogeneity (I2 = 95.52%, P = 0.00). Meta-regression analysis indicated that differences in mean FVIII activity levels in the PVT group, the number of cases in the non-PVT group, and the study design methods partially contributed to the heterogeneity (P < 0.05). However, compared to the non-PVT group, the PVT group had higher FVIII/PC ratio with a statistically significant difference (SMD = 0.39, 95% CI: 0.15 to 0.63, P = 0.00), and there was no significant heterogeneity (I2 = 28.62%).

In conclusion, the FVIII/PC ratio not only reflects the severity of liver disease, but also can be used as one of the predictors of PVT development.

Aim: This study uses blood routine, coagulation and biochemical indicators to explore the relationship between the hematological parameters of patients with various types of liver diseases.Methods: The Kruskal-Wallis, Chi-squared and Fisher exact tests were used to compare the hematological parameters and clinical characteristics of three groups of patients with different degrees of liver disease. Spearman correlation analysis is used to analyze the correlation between two continuous variables. The logistic regression model evaluated the odds ratio between variables and disease changes. Receiver operating characteristic curve analysis was used to understand the predictive value of each index in relation to the progress of liver disease.Results: There are differences in inflammation and coagulation profiles among different types of liver diseases and there is a correlation between them. In addition to the traditional marker α-fetoprotein, the inflammatory marker c-reactive protein and the coagulation marker D-dimer also have good diagnostic value for liver injury.Conclusion: The coagulation and inflammation systems interact, are connected and play essential roles in the liver.

Cirrhosis is a major health concern worldwide with a complex pathophysiology affecting various biological systems, including all aspects of haemostasis. Bleeding risk is mainly driven by portal hypertension, but in end-stage liver disease it is further increased by alterations in haemostatic components, including platelet function, coagulation, and fibrinolysis. Concurrently, patients with cirrhosis are prone to venous thromboembolic events (VTE) because of the altered haemostatic balance, in particular an increase in thrombin generation. In patients with cirrhosis, vitamin K antagonists (VKA) and low molecular weight heparins (LMWH) are currently the standard of care for VTE prevention, with VKA also being standard of care for stroke prevention in those with atrial fibrillation. However, direct oral anticoagulants (DOAC) could have specific advantages in this patient population. Clinical experience suggests that DOAC are a safe and possibly more effective alternative to traditional anticoagulants for the treatment of VTE in patients with compensated cirrhosis. In addition, emerging data suggest that primary prophylactic treatment with anticoagulants may improve clinical outcomes in patients with cirrhosis by reducing the risk of hepatic decompensation. The selection of the most appropriate DOAC remains to be clarified. This review focuses on the rationale for the use of DOAC in patients with cirrhosis, the specific effects of the different DOAC (as assessed by in vitro and in vivo pharmacokinetic and pharmacodynamic studies), as well as clinical outcomes in patients with cirrhosis on DOAC.

Patients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells ex vivo.

Adults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture was assessed by transendothelial resistance measured using the ECIS ZΘ system. Confluent cells from two different endothelial cell donors were stimulated with human serum from liver transplant patients. Pooled serum from healthy men and purified inflammatory agonists served as controls. The permeability response to serum was quantified as the area under the normalized resistance curve. Responses were compared between time points and analyzed for associations with clinical characteristics of liver transplant patients and their grafts.

Liver transplant sera from all time points during surgery-induced permeability in both endothelial cell lines. The magnitude of permeability change was heterogeneous between patients, and there were differences in the effects of sera on the two endothelial cell lines. In one of the cell lines, the severity of liver disease was associated with greater permeability at the start of surgery. In the same cell line, serum collected 15 min after liver reperfusion induced significantly more permeability as compared to that collected at the start of surgery. Early postreperfusion sera from patients undergoing living donor transplants induced more permeability than sera from deceased donor transplants. Sera from two exemplary cases of patients on preoperative dialysis, and one patient with an unexpectedly long warm ischemia time of the liver graft, induced exaggerated and prolonged endothelial permeability.

Serum from patients with cirrhosis undergoing liver transplantation induces permeability of cultured human pulmonary microvascular endothelial cells. Increased endothelial permeability during liver transplantation may contribute to organ injury and present a target for future therapeutics.

Fibrosis, a common cause and serious outcome of organ failure that can affect any organ, is responsible for up to 45% of all deaths in various clinical settings. Both preclinical models and clinical trials investigating various organ systems have shown that fibrosis is a highly dynamic process. Although many studies have sought to gain understanding of the mechanism of fibrosis progression, their findings have been mixed. In recent years, increasing evidence indicates that neutrophil extracellular traps (NETs) are involved in many inflammatory and autoimmune disorders and participate in the regulation of fibrotic processes in various organs and systems. In this review, we summarize the current understanding of the role of NETs in fibrosis development and progression and their possibility as therapeutic targets.

Patients with cirrhosis have a normal to increased thrombin generation (TG) capacity in platelet-poor plasma (PPP). By reflecting the contribution of all circulating blood cells, whole blood (WB) TG may allow a more physiological assessment of coagulation.

We compared WB-TG vs PPP-TG in patients with cirrhosis.

Assessment of coagulation included routine tests, factor VIII, natural anticoagulants, PPP-TG, and WB-TG. TG assays were performed with and without thrombomodulin. Twenty-five healthy subjects were included as controls.

We included 108 patients (Child-Pugh A/B/C, 44/24/40). Compared with controls, patients had significantly lower platelet count, longer international normalized ratio, higher FVIII, and lower levels of protein C/S and antithrombin. Regarding thrombomodulin-modified TG assays, in compensated cirrhosis, both PPP-TG and WB-TG indicated an increased TG capacity, as reflected by an endogenous thrombin potential (ETP) significantly higher than controls. In contrast, in decompensated cirrhosis, PPP-TG indicated a hypercoagulable state with increased ETP, higher peak height, and shorter time-to-peak than controls, whereas WB-TG revealed a progressive impairment of TG kinetics and total capacity, ultimately resulting in a profound hypocoagulable state in patients with Child-Pugh C cirrhosis (ie, significant prolongation of lag time and time-to-peak with reduction of both ETP and peak height). In decompensated patients, bacterial infections and severity of anemia were associated with a further reduction of both ETP and peak height.

Compensated cirrhosis is associated with an increased TG capacity. In decompensated cirrhosis, contrary to PPP-TG, which indicates hypercoagulability, WB-TG shows a significant hypocoagulable state. The clinical value of these findings deserves further investigation.

Patients with cirrhosis develop complex alterations in primary hemostasis that include both hypocoagulable and hypercoagulable features. This includes thrombocytopenia, multiple alterations of platelet function, and increased plasma levels of von Willebrand factor. Contrary to the historical view that platelet dysfunction in cirrhosis might be responsible for an increased bleeding tendency, the current theory posits a rebalanced hemostasis in patients with cirrhosis. Severe thrombocytopenia is not indicative of the bleeding risk in patients undergoing invasive procedures and does not dictate per se the need for pre-procedural prophylaxis. A more comprehensive and individualized risk assessment should combine hemostatic impairment, the severity of decompensation and systemic inflammation, and the presence of additional factors that may impair platelet function, such as acute kidney injury and bacterial infections. Although there are multiple, complex alterations of platelet function in cirrhosis, their net effect is not yet fully understood. More investigations evaluating the association between alterations of platelet function and bleeding/thrombosis may improve risk stratification in patients with decompensated cirrhosis. Besides hemostasis, the assessment of von Willebrand factor Ag and ADP-induced, whole-blood platelet aggregation normalized by platelet count (VITRO score and PLT ratio) are promising biomarkers to predict the risk of hepatic decompensation and survival in both compensated and decompensated patients. Further investigations into the in vivo interplay between platelets, circulating blood elements, and endothelial cells may help advance our understanding of cirrhotic coagulopathy. Here, we review the complex changes in platelets and primary hemostasis in cirrhosis and their potential clinical implications.

 Cirrhotic patients display an increased risk for both bleeding and thrombosis. We investigated platelet activation across Child-Pugh stages (CPSs) and portal hypertension (PH) severity.

 A total of 110 cirrhotic patients were prospectively included. CPS and hepatic venous pressure gradient (HVPG) were determined. Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa were measured by flow cytometry before/after stimulation with protease-activated receptor (PAR)-1 (thrombin receptor activating peptide, TRAP) and PAR-4 (AYPGKF) agonists, epinephrine, and lipopolysaccharide (LPS).

 Platelet count was similar across CPS but lower with increasing PH severity. Expression of P-selectin and activated GPIIb/IIIa in response to TRAP and AYPGKF was significantly reduced in platelets of CPS-B/C versus CPS-A patients (all p < 0.05). Platelet P-selectin expression upon epinephrine and LPS stimulation was reduced in CPS-C patients, while activated GPIIb/IIIa in response to these agonists was lower in CPS-B/C (all p < 0.05). Regarding PH severity, P-selectin and activated GPIIb/IIIa in response to AYPGKF were lower in HVPG ≥20 mmHg patients (both p < 0.001 vs. HVPG < 10 mmHg). Similarly, activated GPIIb/IIIa was lower in HVPG ≥20 mmHg patients after TRAP stimulation (p < 0.01 vs. HVPG < 10 mmHg). The lower platelet surface expression of P-selectin and activated GPIIb/IIIa upon stimulation of thrombin receptors (PAR-1/PAR-4) in CPS-B/C and HVPG ≥20 mmHg patients was paralleled by reduced antithrombin-III levels in those patients (all p < 0.05). Overall, PAR-1- and PAR-4-mediated platelet activation correlated with antithrombin-III levels (p < 0.001).

 Platelet responsiveness decreases with increasing severity of liver cirrhosis and PH but is potentially counterbalanced by lower antithrombin-III levels.

Endothelial dysfunction and portal hypertension (PH) are reflected by increased von Willebrand factor antigen (VWF-Ag) levels in advanced chronic liver disease (ACLD). This study investigated VWF release and cleavage and their association with PH and clinical outcomes.

Levels of VWF-Ag, VWF-N (VWF-propeptide), and VWF-A (VWF processed by the main VWF-cleaving protease ADAMTS13) were assessed in 229 patients with clinically stable ACLD (hepatic venous pressure gradient [HVPG] ≥ 6 mmHg; absence of bacterial infections or acute decompensation) undergoing HVPG-measurement. Liver-healthy individuals served as controls (n = 24).

VWF-Ag and VWF-N were similarly accurate for the identification of clinically significant PH (CSPH; HVPG ≥ 10 mmHg) in compensated ACLD (AUROC: VWF-Ag 0.748; VWF-N 0.728). ADAMTS13 activity was similar between patients with ACLD and controls and did not correlate with PH and disease severity, whereas VWF cleavage decreased in patients with CSPH (i.e., VWF-Ag/-A-ratio increased). In vitro VWF activity strongly reflected VWF-Ag levels (Spearman's r = 0.874, p < 0.001), but decreased (vs. controls) in patients with CSPH when normalized to VWF-Ag levels (VWF-activity/-Ag-ratio). VWF-Act/-Ag ratio correlated negatively with ADAMTS13 activity (r =- 0.256, p < 0.001). ADAMTS13 activity was independently predictive for (i) portal vein thrombosis (PVT) and (ii) hepatic decompensation or liver-related death.

VWF-Ag levels and its propeptide are similarly suitable surrogates of PH in patients with compensated ACLD. ADAMTS13-Act was not linked to disease and PH severity, however, when normalized to VWF-Ag, both VWF cleavage and VWF activity were decreased in patients with CSPH, as compared to liver-healthy individuals. Low ADAMTS13-Act was associated with presumably more procoagulant VWF and adverse outcomes.

NCT03267615.

To investigate the relationship between thrombin-antithrombin complex (TAT), plasmin-α 2-plasmininhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC) and postoperative complications in the early stage after liver transplantation (LT).

We analyzed the perioperative clinical data, including plasma TAT, PIC, sTM, and tPAIC, of 130 post-LT patients admitted to the intensive care unit (ICU), West China Hospital, Sichuan University between December 2021 and November 2022. Patients were divided into two groups, a complication group and a non-complication group, according to whether they experienced complications of Clavien-Dindo (CD) grade Ⅲb and above within 30 days after the surgery. Univariate analysis and binary multivariate logistic regression models were used to determine the risk factors for complications within 30 days post-LT.

The incidence of complications of CD grade Ⅲb and above within 30 days post-LT was 33.1% (43/130). Patients in the complication group had significantly higher scores for the Model for End-Stage Liver Disease (MELD), operative time, intraoperative red blood cell transfusion volume, intraoperative plasma transfusion volume, and plasma TAT, PIC, sTM and tPAIC measured at the time of admission to ICU after the operation than those in the non-complication group did (all P<0.05). Logistic regression showed that for every single U of red blood cells transfused during the transplant surgery, the probabilities of complications within 30 days post-LT increased by 15.1% (95% confidence interval [ C I]: 1.070-1.239, P<0.001) and for the increase of every single TU/mL of plasma sTM measured upon post-LT admission to ICU, the probabilities of complications increased by 13.7% (95% CI: 1.060-1.220, P<0.001).

Plasma sTM measured upon admission to ICU after LT is an independent risk factor for complications within 30 days post-LT, and additional assessment of sTM may help predict complications in the early stage post-LT.

Metabolic syndrome (MetS) is a multifaceted condition that increases the possibility of developing atherosclerotic cardiovascular disease. MetS includes obesity, hypertension, dyslipidemia, hyperglycemia, endothelial dysfunction, and platelet hyperactivity. There is a concerning rise in the occurrence and frequency of MetS globally. The rising incidence and severity of MetS need a proactive, multipronged strategy for identifying and treating those affected. For many MetS patients, achieving recommended goals for healthy fat intake, blood pressure control, and blood glucose management may require a combination of medicine therapy, lifestyles, nutraceuticals, and others. However, it is essential to note that lifestyle modification should be the first-line therapy for MetS. In addition, MetS requires pharmacological, nutraceutical, or other interventions. This review aimed to bring together the etiology, molecular mechanisms, and dietary strategies to combat hypertension, endothelial dysfunction, and platelet dysfunction in individuals with MetS.

Liver cirrhosis is the end-stage liver disease associated with poor prognosis and cardiovascular comorbidity could significantly impact mortality of cirrhotic patients. We conducted a large, retrospective study to investigate the survival impact of cardiovascular co-medications in patients with liver cirrhosis.

A study-specific R package was processed on the local databases of partner institutions within the Observational Health Data Sciences and Informatics consortium, namely Columbia University, New York City (NYC), USA and Ajou University School of Medicine (AUSOM), South Korea. Patients with cirrhosis diagnosed between 2000 and 2020 were included. Final analysis of the anonymous survival data was performed at Medical Faculty Mannheim, Heidelberg University.

We investigated a total of 32,366 patients with liver cirrhosis. Our data showed that administration of antiarrhythmics amiodarone or digoxin presented as a negative prognostic indicator (p = 0.000 in both cohorts). Improved survival was associated with angiotensin-converting enzyme inhibitor ramipril (p = 0.005 in NYC cohort, p = 0.075 in AUSOM cohort) and angiotensin II receptor blocker losartan (p = 0.000 in NYC cohort, p = 0.005 in AUSOM cohort). Non-selective beta blocker carvedilol was associated with a survival advantage in the NYC (p = 0.000) cohort but not in the AUSOM cohort (p = 0.142). Patients who took platelet inhibitor clopidogrel had a prolonged overall survival compared to those without (p = 0.000 in NYC cohort, p = 0.003 in AUSOM cohort).

Concomitant cardiovascular medications are associated with distinct survival difference in cirrhotic patients. Multidisciplinary management is needed for a judicious choice of proper cardiovascular co-medications in cirrhotic patients.

Patients with cirrhosis have a higher risk of severe COVID-19 and mortality and are high-priority patients for vaccination. However, cirrhotics were excluded from the phase 2/3 vaccine trials. Hence, we aimed to assess the antibody response and safety of Covishield (ChAdOx1nCoV-19) among patients with cirrhosis.

Patients who attended the tele-hepatology services at our institute from March 2020 to June 2021 and diagnosed with cirrhosis as per their medical records were telephonically interviewed in July 2021 using a pre-specified questionnaire. Patients who had completed 2 doses of ChAdOx1-nCOV (with the 2^nd dose administered at least 2 weeks back) and without history of documented COVID-19 infection (pre- or post-vaccination) were tested for antibodies against the spike protein. Seropositive patients were divided into high, moderate, and low antibody responses based on the signal/cut-off.

We interviewed 784 patients with cirrhosis. At least 1 dose of ChAdOx1-nCOV was received by 231 patients among whom 134 (58%) had received 2 doses. Documented COVID-19 was reported in 3.9% patients who received at least 1 dose of ChAdOx1-nCOV including breakthrough infections in 3.7% patients vaccinated with 2 doses. Local and systemic adverse events were reported by 42% and 22.1% patients. None developed anaphylaxis, acute decompensation, acute-on-chronic liver failure, or other serious adverse events requiring hospitalization. Seroconversion was documented in 81 (92%) out of 88 patients. No difference was observed in level of antibody response between patients with compensated and decompensated cirrhosis (p = 0.12).

Our preliminary data suggest that ChAdOx1-nCOV is safe with high seroconversion rates in patients with cirrhosis.

Liver cirrhosis is accompanied by several hemostatic alterations, which contribute to the current theory of "rebalanced hemostasis." Splanchnic vein thrombosis (SVT) is a frequent complication of liver cirrhosis (17-26% of the cirrhotic patients), and liver cirrhosis is a common risk factor for SVT (24-28% of SVT cases).

This narrative review aims to describe the current state of the art on the anticoagulant treatment of cirrhotic SVT, with a particular focus on the possible role of the direct oral anticoagulants (DOACs) and recent guidelines on this topic.

Early anticoagulant therapy is recommended in cirrhotic patients with acute SVT, to obtain vessel recanalization and decrease the rates of portal hypertension-related complications. Gastroesophageal varices do not represent a contraindication to anticoagulation, if adequate prophylaxis of variceal bleeding is established, and varices band ligation can be safely performed without the need to stop the anticoagulant treatment. The conventional treatment of cirrhotic SVT consisted of low molecular weight heparin, as initial treatment of choice, eventually followed by vitamin K antagonists, but the DOACs can be considered as a reasonable alternative in patients with compensated liver cirrhosis.

Our retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM.

This study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC).

Univariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM.

A total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all P<0.05). Compared with the control group, female patients, late-onset patients, and HBV-infective patients had lower risks of SLM (HR=0.737, 95%CI: 0.614-0.883, P<0.001; HR=0.752, 95%CI: 0.603-0.943, P=0.013; HR=0.682, 95%CI: 0.473-0.961, P=0.034).

The carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.

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.

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.

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.

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.

Chronic liver disease (CLD) related thrombocytopenia increases the risk of bleeding and poor prognosis. Many liver disease patients require invasive procedures or surgeries, such as liver biopsy or endoscopic variceal ligation, and most of them have lower platelet counts, which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders. Unfortunately, there is no defined treatment modality for CLD-induced thrombocytopenia. Recombinant human thrombopoietin (rhTPO) is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy; however, there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.

To evaluate the efficacy of rhTPO in the treatment of patients with CLD-associated thrombocytopenia undergoing invasive procedures.

All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021. Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia. Adverse events related to treatment, such as bleeding, thrombosis, and disseminated intravascular coagulation, were also investigated.

Among the enrolled patients, 78 (78%) showed a platelet count increase after rhTPO use, while 22 (22%) showed no significant change in platelet count. The mean platelet count after rhTPO treatment in all patients was 101.53 ± 81.81 × 109/L, which was significantly improved compared to that at baseline (42.88 ± 16.72 × 109/L), and this difference was statistically significant (P < 0.001). In addition, patients were further divided into three subgroups according to their baseline platelet counts (< 30 × 109/L, 30-50 × 109/L, > 50 × 109/L). Subgroup analyses showed that the median platelet counts after treatment were significantly higher (P < 0.001, all). Ninety (90%) patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO. No serious adverse events related to rhTPO treatment were observed. Overall, rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.

rhTPO can improve platelet count, reduce the risk of bleeding, and decrease the platelet transfusion rate, which may promote the safety of invasive procedures and improve overall survival of patients with CLD.

Studies on platelet aggregation in cirrhosis are controversial because interpretation of platelet function is challenged by thrombocytopenia. We conducted a prospective study to investigate whole blood platelet aggregation in cirrhosis and its association with liver-related outcomes.

Platelet aggregation was assessed by whole blood aggregometry (Multiplate®). To overcome the influence of platelet count and compare cirrhosis with thrombocytopenia vs. controls with normal platelet count, we calculated a ratio between platelet aggregation and platelet count (PLT ratio). Then, we prospectively followed patients with cirrhosis and ascertained predictors of decompensation, transplantation, and death.

Two-hundred and three patients with cirrhosis were prospectively recruited (77% decompensated). PLT ratio was significantly higher in cirrhosis than in those with chronic hepatitis and healthy individuals (0.44 vs. 0.25 and 0.26, respectively; p <0.0001). In cirrhosis, the ratio increased with disease severity (Child-Pugh class C>B>A) and was particularly elevated in decompensated patients with severe thrombocytopenia. Among decompensated patients, 65 had further decompensation, underwent transplantation, or died during a 6-month follow-up. On multivariate analysis, PLT ratio (odds ratio 1.87; 95% CI 1.23-2.84; p = 0.003) and MELD score (odds ratio 1.05; 95% CI 1.01-1.08; p = 0.01) were independently associated with outcome. The relative risk of events was 7.5-fold higher in patients with PLT ratio >0.75 vs. patients with PLT ratio <0.25 (95% CI 2.5-21.9; p = 0.003). The increased PLT ratio, its discriminative ability for composite outcome, and the prognostic value of PLT ratio >0.75 were confirmed in an independent cohort of hospitalized patients with decompensated cirrhosis (n = 41).

Patients with cirrhosis, particularly when decompensated, exhibit significantly increased whole blood platelet aggregation. Decompensated patients with a PLT ratio >0.75 have a >80% probability of further decompensation, transplantation, or liver-related death within 6 months.

In patients with cirrhosis, previous studies have suggested that platelets (i.e. circulating blood cells that help form clots to stop bleeding) are dysfunctional. In particular, these studies suggested that platelet aggregation (the process by which platelets adhere to each other to form clots) is reduced. Since platelet aggregation is important for clot formation, it has been hypothesized that alterations of platelet aggregation may be responsible for the increased risk of bleeding observed in patients with cirrhosis. Our study demonstrates: i) that platelet aggregation in patients with cirrhosis is higher than in healthy individuals; ii) that platelet aggregation in patients with decompensated cirrhosis (i.e. those who have already experienced some complications of cirrhosis) is particularly elevated and associated with risk of further complications and death.

Cirrhotic patients have an increased risk of bleeding and thromboembolic events, with platelets being involved as key players in both situations. The impact of peripheral versus central blood sampling on platelet activation remains unclear. In 33 cirrhotic patients, we thus analyzed platelet function in peripheral (P) and central (C) blood samples. Platelet surface expression of P-selectin, activated glycoprotein (GP) IIb/IIIa, and leukocyte-platelet aggregate formation were measured by flow cytometry in response to different agonists: thrombin receptor-activating peptide-6, adenosine diphosphate, collagen-related peptide (CrP), epinephrine, AYPGKF, Pam3CSK4, and lipopolysaccharide. Unstimulated platelet surface expression of P-selectin (p = .850) and activated GPIIb/IIIa (p = .625) were similar in peripheral and central blood samples. Stimulation with various agonists yielded similar results of platelet surface expression of P-selectin and activated GPIIb/IIIa in peripheral and central samples, except for CrP-inducible expression of activated GPIIb/IIIa (median fluorescence intensity, MFI in P: 7.61 [0.00-24.66] vs. C: 4.12 [0.00-19.04], p < .001). The formation of leukocyte-platelet aggregate was similar in central and peripheral blood samples, both unstimulated and after stimulation with all above-mentioned agonists. In conclusion, peripheral vs. central venous blood sampling does not influence the assessment of platelet activation by flow cytometry in cirrhosis.Abbreviations: ACLD: advanced chronic liver disease; ADP: adenosine diphosphate; ALD: alcoholic liver disease; AYPGKF: PAR-4 agonist AYPGKF; CrP: collagen related protein; EPI: epinephrine; FACS: fluorescence-activated cell sorting; GP: glycoprotein; HVPG: hepatic venous pressure gradient; IQR: interquartile range; LPS: lipopolysaccharide; LSM: liver stiffness measurement; MFI: median fluorescence intensity; NAFLD: nonalcoholic fatty liver disease; PAM: lipopeptide Pam3CSK4; PAR: protease-activated receptor; PBS: phosphate-buffered saline; PH: portal hypertension; TIPS: transjugular intrahepatic portosystemic stent shunt; TLR: toll-like receptor; TRAP-6: thrombin receptor-activator peptide-6; vWF: von Willebrand factor.

Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.

Bacterial infections in cirrhosis are associated with increased bleeding risk. To assess the factors responsible for bleeding tendency in patients with bacterial infections, we conducted a prospective study comparing all 3 aspects of hemostasis (platelets, coagulation, and fibrinolysis) in hospitalized patients with decompensated cirrhosis with vs. without bacterial infections.

Primary hemostasis assessment included whole blood platelet aggregation and von Willebrand factor (VWF). Coagulation assessment included procoagulant factors (fibrinogen, factor II, V, VII, VIII, IX, X, XI, XII, XIII), natural anticoagulants (protein C, protein S, antithrombin) and thrombomodulin-modified thrombin generation test. Fibrinolysis assessment included fibrinolytic factors (plasminogen, t-PA, PAI-1, α2-AP, TAFIa/ai) and plasmin-antiplasmin complex (PAP).

Eighty patients with decompensated cirrhosis were included (40 with and 40 without bacterial infections). Severity of cirrhosis and platelet count were comparable between groups. At baseline, patients with cirrhosis and bacterial infections had significantly lower whole blood platelet aggregation, without significant differences in VWF. Regarding coagulation, bacterial infections were associated with reduced procoagulant factors VII and XII, and a significant reduction of all natural anticoagulants. However, thrombomodulin-modified thrombin generation was comparable between the study groups. Finally, although mixed potentially hypo-fibrinolytic (lower plasminogen) and hyper-fibrinolytic (higher t-PA) changes were present in bacterial infections, a comparable level of PAP was detected in both groups. Upon resolution of infection (n = 29/40), platelet aggregation further deteriorated whereas coagulation and fibrinolysis factors returned to levels observed in patients without bacterial infections.

In hospitalized patients with decompensated cirrhosis, bacterial infections are associated with reduced whole blood platelet aggregation and a significant decrease of all natural anticoagulants, which may unbalance hemostasis and potentially increase the risk of both bleeding and thrombosis.

Bacterial infections are a common issue in hospitalized patients with decompensated cirrhosis (i.e. patients hospitalized due to severe complications of advanced chronic liver disease). Patients with decompensated cirrhosis who acquire infections may be at increased risk of bleeding complications following invasive procedures (that is a procedure in which the body is penetrated or entered, for instance by a needle or a tube). As bleeding complications in decompensated cirrhosis are associated with a high risk of further decompensation and death, there is an urgent need to understand the factors responsible for such increased bleeding tendency. Herein, we investigated the alterations of hemostasis (that is the physiological process responsible for clot formation and stability) in patients with decompensated cirrhosis and bacterial infections. We found that development of bacterial infections in these patients is associated with alterations of hemostasis (particularly of platelets and clotting cascade) that may increase the risk of both bleeding and thrombotic complications.

Venous thrombosis is a frequent complication in cancer and is associated with high morbidity and mortality. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related death worldwide, and it is associated with preexisting cirrhosis in 90% of cases. Patients with cirrhosis acquire complex alterations in their haemostatic system that may predispose them to bleed or thrombotic complications. There is growing evidence that HCC may tilt the haemostatic equilibrium in cirrhosis towards hypercoagulability, thus increasing the risk of venous thrombosis. Previously described mechanisms of HCC-driven thrombophilia include thrombocytosis and increased platelet activation/function, increased fibrinogen concentration/polymerization, enhanced thrombin generation, hypofibrinolysis, and release of tissue factor-expressing microvesicles. Nevertheless, there are currently no specific guidelines on risk stratification and management of thromboprophylaxis in patients with cirrhosis and HCC. Our review endeavours to summarize the latest findings on epidemiology, risk factors and pathogenesis of non-malignant venous thrombosis in patients with cirrhosis and HCC, and provide evidence in support of tailored management of thrombotic risk in these patients.

Anticoagulation and antiplatelet therapies are increasingly used in liver transplant (LT) candidates and recipients due to cardiovascular comorbidities, portal vein thrombosis, or to manage posttransplant complications. The implementation of the new direct-acting oral anticoagulants and the recently developed antiplatelet drugs is a great challenge for transplant teams worldwide, as their activity must be monitored and their complications managed, in the absence of robust scientific evidence. In this changing and clinically heterogeneous scenario, the Spanish Society of Liver Transplantation and the Spanish Society of Thrombosis and Haemostasis aimed to achieve consensus regarding the indications, drugs, dosing, and timing of anticoagulation and antiplatelet therapies initiated from the inclusion of the patient on the waiting list to post-LT surveillance. A multidisciplinary group of experts composed by transplant hepatologists, surgeons, hematologists, transplant-specialized anesthesiologists, and intensivists performed a comprehensive review of the literature and identified 21 clinically relevant questions using the patient-intervention-comparison-outcome format. A preliminary list of recommendations was drafted and further validated using a modified Delphi approach by a panel of 24 transplant delegates, each representing a LT institution in Spain. The present consensus statement contains the key recommendations together with the core supporting scientific evidence, which will provide guidance for improved and more homogeneous clinical decision making.

Serum concentrations of 25-hydroxyvitamin D (25(OH)VD) and C-reactive protein (CRP) and von Willebrand's factor (vWF) concentration correlate with histopathologic disease grade and stage in chronic inflammatory and fibrotic hepatopathies (CH) in humans.

To evaluate serum 25(OH)VD and serum CRP concentrations and plasma vWF concentration and determine if they correlate with histopathologic and biochemical variables in dog with CH.

Twenty-three client-owned dogs with a histopathologic diagnosis of CH were prospectively enrolled.

Blood samples were collected before liver biopsy. Correlations between biomarkers and clinical pathological and histopathologic variables were evaluated using Pearson's or Spearman's test.

Serum 25(OH)VD concentration (median, 213 nmol/L; range, 42-527 nmol/L) was negatively correlated with serum aspartate aminotransferase activity (AST; rho = -0.59, P < .01), polymorphonuclear neutrophil count (PMN; r = -0.46, P < .05), and positively correlated with serum albumin concentration (r = 0.69, P < .001). Serum CRP concentration (median, 7.4 μg/L; range, 1-44.9 μg/L) was positively correlated with overall histopathologic necroinflammatory activity (r = 0.78, P < .001) and fibrosis score (rho = 0.49, P < .05). Plasma vWF concentration (median, 73.3%; range, 15-141%) was positively correlated with fibrosis score (r = 0.53, P < .05) and prothrombin time (rho = 0.67, P < .01), and negatively correlated with serum albumin concentration (r = -0.73, P < .001).

In dogs with CH, serum 25(OH)VD concentration was negatively correlated with disease activity, whereas serum CRP concentration and plasma vWF concentration were positively correlated with histopathologic grade and stage. Our results provide preliminary evidence that these biomarkers may be useful to assess grade and stage of CH in dogs in the absence of liver biopsy.

Critical care is rapidly evolving with significant innovations to decrease hospital stays and costs. To our knowledge, there is limited data on factors that affect the length of stay and hospital charges in cirrhotic patients who present with ST-elevation myocardial infarction-related cardiogenic shock (SRCS).

To identify the factors that increase inpatient mortality, length of stay, and total hospital charges in patients with liver cirrhosis (LC) compared to those without LC.

This study includes all adults over 18 from the National Inpatient Sample 2017 database. The study consists of two groups of patients, including SRCS with LC and without LC. Inpatient mortality, length of stay, and total hospital charges are the primary outcomes between the two groups. We used STATA 16 to perform statistical analysis. The Pearson's chi-square test compares the categorical variables. Propensity-matched scoring with univariate and multivariate logistic regression generated the odds ratios for inpatient mortality, length of stay, and resource utilization.

This study includes a total of 35798453 weighted hospitalized patients from the 2017 National Inpatient Sample. The two groups are SRCS without LC (n = 758809) and SRCS with LC (n = 11920). The majority of patients were Caucasian in both groups (67% vs 72%). The mean number of patients insured with Medicare was lower in the LC group (60% vs 56%) compared to the other group, and those who had at least three or more comorbidities (53% vs 90%) were significantly higher in the LC group compared to the non-LC group. Inpatient mortality was also considerably higher in the LC group (28.7% vs 10.63%). Length of Stay (LOS) is longer in the LC group compared to the non-LC group (9 vs 5.6). Similarly, total hospital charges are higher in patients with LC ($147407.80 vs $113069.10, P ≤ 0.05). Inpatient mortality is lower in the early percutaneous coronary intervention (PCI) group (OR: 0.79 < 0.11), however, it is not statistically significant. Both early Impella (OR: 1.73 < 0.05) and early extracorporeal membrane oxygenation (ECMO) (OR: 3.10 P < 0.05) in the LC group were associated with increased mortality. Early PCI (-2.57 P < 0.05) and Impella (-3.25 P < 0.05) were also both associated with shorter LOS compared to those who did not. Early ECMO does not impact the LOS; however, it does increase total hospital charge (addition of $24717.85, P < 0.05).

LC is associated with a significantly increased inpatient mortality, length of stay, and total hospital charges in patients who develop SRCS. Rural and Non-teaching hospitals have significantly increased odds of extended hospital stays and higher adjusted total hospital charges. The Association of LC with worse outcomes outlines the essential need to monitor these patients closely and treat them early on with higher acuity care. Patients with early PCI had both shorter LOS and reduced inpatient mortality, while early Impella was associated with increased mortality and shorter LOS. Early ECMO is associated with increased mortality and higher total hospital charges. This finding should affect the decision to follow through with interventional management in this cohort of patients as it is associated with poor outcomes and immense resource utilization.

In recent years, the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved. Currently, it is known that in cirrhotic patients, the hemostatic system is rebalanced, which involves coagulation factors, fibrinolysis and platelets. These alterations disrupt homeostasis, skewing it toward a procoagulant state, which can lead to thromboembolic manifestations, especially when hemodynamic and endothelial factors co-occur, such as in the portal vein system in cirrhosis. Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease, prognosis of cirrhotic patients and success of liver transplantation. It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function. Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis. In chronic portal vein thrombosis, the role of anticoagulant therapy is still unclear. Traditional anticoagulants, vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis. In the last ten years, direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolic-related diseases, but evidence on their use in cirrhotic patients is very limited. The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.

Patients with liver diseases are in a rebalanced state of hemostasis, due to simultaneous decline in pro- and anticoagulant factors. This balance seems to remain even in the sickest patients, but is less stable and might destabilize when patients develop disease complications. Patients with acute decompensation of cirrhosis, acute-on-chronic liver failure, or acute liver failure often develop complications associated with changes in the hemostatic system, such as systemic inflammation. Systemic inflammation causes hemostatic alterations by adhesion and aggregation of platelets, release of von Willebrand factor (VWF), enhanced expression of tissue factor, inhibition of natural anticoagulant pathways, and inhibition of fibrinolysis. Laboratory tests of hemostasis in acutely-ill liver patients may indicate a hypocoagulable state (decreased platelet count, prolongations in prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels) due to decreased synthetic liver capacity or consumption, or a hypercoagulable state (increased VWF levels, hypofibrinolysis in global tests). Whether these changes are clinically relevant and should be corrected with antithrombotic drugs or blood products is incompletely understood. Inflammation and activation of coagulation may cause local ischemia, progression of liver disease, and multiorgan failure. Anti-inflammatory treatment in acutely-ill liver patients may be of potential interest to prevent thrombotic or bleeding complications and halt progression of liver disease.

Management of coagulopathy in patients with advanced liver disease undergoing therapeutic endoscopic procedures is complex. Improvements in the understanding of hemostasis at a physiologic level have highlighted the inaccuracy of currently available clinical tests, like platelet count and prothrombin time, in estimating hemostasis in patients with cirrhosis. With identification of novel factors that contribute to bleeding risk in patients with cirrhosis, there is a dearth of clinical trial data that account for all potentially relevant factors and that examine interventions to reduce bleeding risk. Precise recommendations regarding transfusion strategies based on hemostatic test results in patients with cirrhosis are impractical.

In patients with cirrhosis with severe thrombocytopenia (platelet count [PC] <50 × 109 /L) and undergoing invasive procedures, it is common clinical practice to increase the PC with platelet transfusions or thrombopoietin receptor agonists to reduce the risk of major periprocedural bleeding. The aim of our study was to investigate the association between native PC and perioperative bleeding in patients with cirrhosis undergoing surgical procedures for the treatment of hepatocellular carcinoma (HCC). We retrospectively evaluated 996 patients with cirrhosis between 1996 and 2018 who underwent surgical treatments of HCC by liver resection (LR) or radiofrequency ablation (RFA) without prophylactic platelet transfusions. Patients were allocated to the following three groups based on PC: high (>100 × 109 /L), intermediate (51-100 × 109 /L), and low (≤50 × 109 /L). PC was also analyzed as a continuous covariate on multivariable analysis. The primary endpoint was major perioperative bleeding. The overall event rate of major perioperative bleeding was 8.9% and was not found to differ significantly between the high, intermediate, and low platelet groups (8.1% vs. 10.2% vs. 10.8%, P = 0.48). On multivariable analysis, greater age, aspartate aminotransferase, lower hemoglobin, and treatment with LR (vs. RFA) were found to be significant independent predictors of major perioperative bleeding, with associations with disease etiology and year of surgery also observed. After adjusting for these factors, the association between PC and major perioperative bleeding remained nonsignificant. Conclusion: Major perioperative bleeding was not significantly associated with PC in patients with cirrhosis undergoing surgical treatment of HCC, even when their PC was <50 × 109 /L. With the limit of a retrospective analysis, our data do not support the recommendation of increasing PC in patients with severe thrombocytopenia in order to decrease their perioperative bleeding risk.