An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis

Background & Aims: Patients with cirrhosis have an increased tendency to develop thromboses despite the longer coagulation times of their plasma, compared with that of healthy individuals. We investigated whether plasma from cirrhotic patients has an imbalance of pro- vs anti-coagulation factors. Methods: We analyzed blood samples from 134 cirrhotic patients and 131 healthy subjects (controls) for levels of pro- and anti-coagulants and for thrombin generation in the presence or absence of thrombomodulin (the main physiologic activator of the protein C anticoagulant pathway). Results: The median ratio of thrombin generation (with/without thrombomodulin) was higher in patients (0.80; range, 0.51–1.06) than controls (0.66; range, 0.17–0.95), indicating that cirrhotic patients are resistant to the action of thrombomodulin. This resistance resulted in greater hypercoagulability of plasma from patients of Child–Pugh class C than of class A or B. The hypercoagulability of plasma from patients of Child–Pugh class C (0.86; range, 0.70–1.06) was slightly greater than that observed under the same conditions in patients with congenital protein C deficiency (0.76; range, 0.60–0.93). Levels of factor VIII, a potent pro-coagulant involved in thrombin generation, increased progressively with Child–Pugh score (from Child–Pugh class A to C). Levels of protein C, one of the most potent naturally occurring anti-coagulants, showed the opposite trend. Conclusions: The hypercoagulability of plasma from patients with cirrhosis appears to result from increased levels of factor VIII and decreased levels of protein C—typical features of patients with cirrhosis. These findings might explain the risk for venous thromboembolism in patients with chronic liver disease.