Increased Thrombin Generation Predicts First Decompensation in Compensated Cirrhosis: Hepatology Communications | August 2026

Introduction:

Cirrhosis is no longer considered simply a bleeding disorder but a state of rebalanced and sometimes prothrombotic haemostasis. Whether this hypercoagulable phenotype contributes directly to disease progression remains uncertain. This study evaluated whether thrombomodulin-modified thrombin generation (TM-TG) predicts first hepatic decompensation in patients with compensated cirrhosis.

Why was this study needed?

INR does not adequately reflect the complex haemostatic balance in cirrhosis.

Increased thrombin generation may promote intrahepatic microthrombosis and disease progression.

Previous studies largely focused on already decompensated patients.

Identifying coagulation-related predictors could reveal new therapeutic targets in compensated cirrhosis.

Results:

Among 171 patients with compensated cirrhosis, 22% developed their first hepatic decompensation over a median 3.3 years.

Patients who decompensated demonstrated significantly greater thrombin generation, along with lower platelets and more frequent large varices.

Increased TM-TG remained independently associated with decompensation after accounting for MELD, platelet count, and large varices.

A high thrombin-generation ratio was associated with approximately a threefold greater risk of first decompensation.

Clinical Impact:

These findings strengthen the concept that coagulation abnormalities may actively contribute to cirrhosis progression, rather than simply reflecting advanced liver disease. TM-TG could potentially improve risk stratification beyond conventional markers and provides further biological rationale for investigating anticoagulation as a disease-modifying strategy. However, these data do not justify routine anticoagulation in compensated cirrhosis.

Bottom Line:

A hypercoagulable phenotype characterized by increased thrombin generation independently predicts first hepatic decompensation in compensated cirrhosis. Coagulation may therefore represent both a biomarker and a potential mechanistic driver of disease progression, warranting prospective validation and therapeutic trials.