Prothrombin conversion and thrombin decay in patients with cirrhosis-role of prothrombin and antithrombin deficiencies

J Thromb Haemost. 2024 May;22(5):1347-1357. doi: 10.1016/j.jtha.2024.01.016. Epub 2024 Feb 1.


Background: Thrombin generation (TG) in the presence of thrombomodulin (TG-TM) in the plasma of patients with cirrhosis (PWC) is tilted toward a hypercoagulable phenotype. Low protein C and elevated factor VIII levels play a role, but other determinants, such as the prothrombin/antithrombin pair, must also be studied.

Objectives: The objectives were (i) to quantitatively assess the subprocesses (prothrombin conversion and thrombin decay) and (ii) to understand the underlying mechanism by studying TG dynamics after prothrombin and antithrombin plasma level correction in PWC.

Methods: We studied TG-TM in plasma samples of 36 healthy controls (HCs) and 41 PWC with prothrombin and antithrombin levels of <70% and after their correction. We initiated coagulation with an intermediate picomolar concentration of tissue factor. We determined the overall thrombin potential, prothrombin conversion, and thrombin decay.

Results: TG-TM was increased in PWC compared with HC due to impaired thrombin inhibition. Indeed, thrombin decay capacity (min-1) decreased from 0.37 (0.35-0.40) in HC to 0.33 (0.30-0.37) in the Child-Turcotte-Pugh A (CTP-A; P = .09), 0.27 (0.26-0.30) in the CTP-B (P < .001), and 0.20 (0.19-0.20) in the CTP-C (P < .001) group. Concomitant correction of prothrombin and antithrombin increased endogenous thrombin potential with prothrombin conversion surpassing thrombin decay. By contrast, when we corrected only antithrombin, TG-TM was normalized and even consistent with a hypocoagulable phenotype in the CTP-C group.

Conclusion: Our results highlight that in PWC, hypercoagulability (evidenced in the presence of TM) is due to impaired thrombin decay, whereas low prothrombin levels do not translate into decreased prothrombin conversion, likely due to altered TM-activated protein C negative feedback.

Keywords: antithrombin; cirrhosis; hypercoagulability; prothrombin; thrombin; thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antithrombins / blood
  • Blood Coagulation Tests
  • Blood Coagulation*
  • Case-Control Studies
  • Female
  • Humans
  • Liver Cirrhosis* / blood
  • Liver Cirrhosis* / diagnosis
  • Male
  • Middle Aged
  • Phenotype
  • Prothrombin*
  • Thrombin* / metabolism
  • Thrombomodulin / blood
  • Thromboplastin / metabolism


  • Prothrombin
  • Thrombin
  • Thrombomodulin
  • Antithrombins
  • Thromboplastin
  • THBD protein, human