Coagulation factor defects,
thrombocytopenia, and
thrombocytopathy are associated with
cirrhosis. However,
bleeding in patients who have
cirrhosis does not entirely correlate with abnormal coagulation tests. Recently, it was shown that because of the concomitant abnormalities of the procoagulant and
anticoagulant drives,
thrombin generation in plasma patients with
cirrhosis is normal when assessed with assays that include
thrombomodulin (the main
protein C activator). However,
thrombin is also generated in vivo as a function of platelets, suggesting that
thrombocytopenia and
thrombocytopathy might affect
thrombin generation in patients with
cirrhosis. We addressed this issue using an assay that accounts for the contribution of plasma and platelets. The study showed that platelet-rich plasma with platelets adjusted by dilution of autologous platelet-rich into autologous platelet-poor plasma to a standard count (100 x 10(9)/L) generates as much
thrombin in patients with
cirrhosis as in controls (1,063 nmol/L vs. 1,167 nmol/L; P value not significant). When platelets were adjusted to correspond to whole-blood counts, patients with
cirrhosis generated significantly less
thrombin than controls (949 nmol/L vs. 1,239 nmol/L; P < .001). Furthermore,
thrombin generation correlated with platelet numbers (rho = 0.50; P < .001). In addition, the amount of
thrombin generated as a function of the whole-blood patients' platelet counts increased significantly when the numbers were adjusted to 100 x 10(9)/L (953 nmol/L vs.1,063 nmol/L; P < .001). In conclusion, severe
thrombocytopenia may limit
thrombin generation in patients with
cirrhosis. These findings might justify
platelet transfusion in patients with low platelet counts when they bleed spontaneously or before undergoing surgery or liver biopsy. Controlled clinical trials supporting this indication are warranted.