Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis

Abstract

Owing to PVT results from the pro-coagulant imbalance occurring in patients with advanced cirrhosis, TM-R might serve as a predictor and could possibly be a biological mediator of adverse outcome in patients with advanced cirrhosis.

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis

“…High levels of von Willebrand factor is a distinct feature of patients with cirrhosis and studies have shown its role as a predictor of clinical outcome in this setting . In this study, we show that plasma von Willebrand factor is significantly decreased in patients with cirrhosis treated with DAAs and this should be considered as an additional beneficial effect of these drugs.…”

“…This procoagulant imbalance, which was independently confirmed depends on the elevated levels of factor VIII, reduced levels of protein C and the increased factor VIII/protein C ratio, which are typical features of patients with cirrhosis. Recent studies showed that the procoagulant imbalance detected as an increased factor VIII/protein C ratio independently predicts outcome in patients with cirrhosis and that the resistance to thrombomodulin is associated with an increased risk of developing de novo portal vein thrombosis …”

Phosphatidylserine on blood cells and endothelial cells contributes to the hypercoagulable state in cirrhosis

“…Many studies have demonstrated that cirrhotic patients have a higher risk of venous thromboembolism than healthy subjects . Other studies have shown that resistance to thrombomodulin, increased factor VIII to protein C ratio, and lower level of antithrombin in cirrhosis may lead to increased thrombosis risk . However, excess exogenous phospholipid was added during the course of these studies.…”

Non-neoplastic portal vein thrombosis in HCV cirrhosis: the weight of inflammation on a fragile hemostatic balance

“…At today, we have learnt that the procoagulant imbalance described in cirrhosis is sustained by high levels of factor VIII/protein C ratio and low levels of anticoagulants all correlating with the degree of plasma in vitro resistance to the action of thrombomodulin. These pro-hemostatic features are associated with worse prognosis, progression of the disease and translocation of bacterial products (7,(20)(21)(22). A relevant weakness of the study by El-Makarem lies on the absence of measurement of these factors, as they are crucial players in the hemostatic balance, beside FVII (and FVII-AT complexes).…”

“…Moreover, plasma from patients with cirrhosis shows a pro-coagulant imbalance alongside disease severity, as expressed by the resistance to the action of thrombomodulin, a strong anti-coagulant factor (5). These pro-hemostatic properties are also associated with severe prognosis and probably concur in the worsening of liver function as consequence of liver microthrombosis and progressive parenchymal extinction (6,7). As a matter of fact, in a cardinal randomized controlled trial by Villa et al, the use of enoxaparin was associated with better survival and less events of decompensation, along with portal vein thrombosis (PVT) prevention (8).…”