Preservation of thrombin generation in cirrhosis despite abnormal results of international normalized ratio: implications for invasive procedures

Abstract

 

Thrombin generation is normal or elevated in patients with cirrhosis when tested in the presence of thrombomodulin, the activator of the main natural anticoagulant protein C. However, the relationship between thrombin generation with bleeding has been little explored in literature. 97 Consecutive patients with cirrhosis were prospectively included (58 men; 54 ± 10 years) and divided into two groups international normalized ratio (INR) less than 1.5 (n = 72) or INR at least 1.5 (n = 25). 46 Healthy individuals were tested as controls. Endogenous thrombin potential (ETP) was measured without and with the addition of thrombomodulin. ETP measured without thrombomodulin was reduced in patients with cirrhosis when compared with controls, but no significant difference was found between the INR less than 1.5 and INR at least 1.5 groups (1250 ± 315.7 versus 1186 ± 238 nmol/l × min; P = 0.3572). After the addition of thrombomodulin, both groups generated thrombin comparable with controls (INR ≥ 1.5: 965.9 ± 232.3; INR < 1.5: 893.0 ± 368.6; controls: 915.0 ± 458 nmol/l × min). 80% of patients had high ETP without/with thrombomodulin ratio, demonstrating the resistance to the anticoagulant action of thrombomodulin for both groups. This was more marked in the INR at least 1.5 group (0.81 ± 0.1 versus 0.69 ± 0.2; P = 0.0042). Postligation of esophageal varices bleeding occurred in 5.2% of patients (INR < 1.5, n = 3; INR ≥ 1.5, n = 2), all of them with ETP without/with thrombomodulin ratio ranging from 0.72 to 0.90 (controls 0.57 ± 0.21). This study confirms that thrombin generation in the presence of thrombomodulin was normal in most patients with cirrhosis, including those with high INR value, but did not correlate with postligation of esophageal varices bleeding.