Patients with cirrhosis show a relative increase in thrombin generation that is correlated with lower antithrombin levels.

Abstract

Predicting the risk of bleeding or thrombosis in cirrhotic patients is difficult due to reduced levels and dysregulation of both procoagulant and anticoagulant factors. We utilized thrombin generation and microvesicle analysis to better understand the regulation of haemostasis in cirrhotic patients. We studied 24 patients with cirrhosis vs. 21 healthy controls. Cirrhotic patients had reduced prothrombin activity (40 ± 9 vs. 112 ± 15), protein C activity (36 ± 10 vs. 114 ± 19) and antithrombin activity (43 ± 14 vs. 109 ± 10). Peak thrombin generation was reduced in cirrhotic patients (165 ± 47 vs. 232 ± 101), but the ratio of peak thrombin generation to prothrombin activity was increased in cirrhotic patients (4.2 ± 1.0 vs. 2.1 ± 0.9) indicating a relative increase in thrombin generation in cirrhosis. The termination time ratio was increased in cirrhotic patients (7.2 ± 1.9 vs. 3.1 ± 0.7) and correlated with reduced antithrombin levels, indicating that cirrhotic patients took longer to stop thrombin generation than controls. Cirrhotic patients showed reduced procoagulant microvesicles from platelets (39 500 ± 24 800 vs. 107 700 ± 74 200) and other cells, but levels overlapped with controls. Cirrhotic patients showed a wide range of procoagulant and anticoagulant levels leading to variability in the regulation of thrombin generation. In conclusion, compared with healthy controls, patients with cirrhosis have lower antithrombin levels that lead to slower downregulation of thrombin generation and more overall thrombin being produced for a given procoagulant level in blood, but also low normal levels of procoagulant microvesicles that would slow initiation of thrombin generation. Whether an individual cirrhosis patient is at a greater risk of bleeding vs. thrombosis may depend on their specific imbalance in procoagulants vs. anticoagulants.