Hypercoagulation and thrombophilia in liver disease

Abstract

A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well-known bleeding diathesis of liver disease. These events may be clinically evident, such as in portal vein thrombosis or pulmonary embolism, but these conditions may also be a silent contributor to certain disease states, such as portopulmonary hypertension or parenchymal extinction with liver atrophy as well as thrombosis of extracorporeal circuits in dialysis or liver assist devices. Moreover, liver disease-related hypercoagulability may contribute to vascular disease in the increasingly common condition of non-alcoholic fatty liver disease. Despite the incidence of these problems, there are few widely accessible and practical laboratory tests to evaluate the risk of a hypercoagulable event in cirrhosis patients. Furthermore, there is little research on the use of commonly accepted anticoagulants in patients with liver disease. This article is a result of an international symposium on coagulation disorders in liver disease and addresses several areas of specific interest in hypercoagulation in liver disease. Critical areas lacking clinical information are highlighted and future areas of research interest are defined with an aim to foster clinical research in this field.

Deep vein thrombosis in patients with advanced liver cirrhosis: a rare condition?

“…Besides, decreased synthesis of the natural anticoagulants, hypercoagulation in liver disease, could also be related to poor flow and vasculopathy associated with a chronic inflammatory state. The potential disease state favoring DVT or PE in patients with liver cirrhosis could be an imbalance of clotting cascade favoring coagulation, immobility of endstage liver disease, infection, and systemic inflammation [14]. Clinical pretest probability, developed by Wells et al [15], stratified patients into low, moderate, and high risks of DVT.…”

Crucial Role of ADAMTS13 Related to Endotoxemia and Subsequent Cytokinemia in the Progression of Alcoholic Hepatitis

“…Portal or hepatic vein thrombosis is often observed in advanced LC (Amitrano et al, 2004;Wanless et al, 1995), and microthrombi formation is seen in one or multiple organs in one-half of autopsied cirrhotic patients (Oka & Tanaka, 1979). Such a hypercoagulable state in liver diseases may be involved in hepatic parenchymal destruction, the acceleration of liver fibrosis and disease progression (Northup et al, 2008;Pluta et al, 2010).…”

“…Locally, the SEC dysfunction could lead to the development of a hypercoagulable state at the hepatic sinusoids corresponding to the site of liver injury, even in the presence of a systemic hypocoagulable state (Northup et al, 2008). Considering that ADAMTS13 is synthesized in HSCs and its substrate, UL-VWFM, is produced in transformed SECs during liver injury, decreased plasma ADAMTS13:AC may involve not only sinusoidal microcirculatory disturbances, but also subsequent progression of liver diseases, finally leading to multiorgan failure.…”

“…A deficiency of anticoagulant proteins (antithrombin, protein C and protein S) and the high levels of several procoagulant factors (Factor VIII and VWF) may contribute to hypercoagulability in advanced liver diseases (Northup et al, 2008). Locally, the SEC dysfunction could lead to the development of a hypercoagulable state at the hepatic sinusoids corresponding to the site of liver injury, even in the presence of a systemic hypocoagulable state (Northup et al, 2008).…”

Surgery in a Patient with Liver Disease

“…59,60 Thrombotic complications in cirrhosis manifest usually as deep vein thrombosis, pulmonary embolism, and acute portal vein thrombosis. These can be carefully and safely treated with anticoagulants.…”