Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy

J Thromb Haemost. 2010 Sep;8(9):1994-2000. doi: 10.1111/j.1538-7836.2010.03937.x.


Background: Prothrombin time (PT) and the international normalized ratio (INR) are still routinely measured in patients with liver cirrhosis to 'assess' their bleeding risk despite the lack of correlation with the two. Thrombin generation (TG) assays are global assays of coagulation that are showing promise in assessing bleeding and thrombosis risks.

Aim: To study the relationship between the INR and TG profiles in cirrhosis-induced coagulopathy.

Methods: Seventy-three patients with cirrhosis were studied. All TG parameters were compared with those from a normal control group. Contact activation was prevented using corn trypsin inhibitor. TG was also assayed in the presence of Protac(®). The endogenous thrombin potential (ETP) ratio was derived by dividing the ETP with Protac® by the ETP without Protac®.

Results: The INR (mean 1.7) did not correlate with the ETP and the velocity of TG (P > 0.05). There was no difference between the lag time and ETP of the two groups (P > 0.05). The velocity of TG was increased in cirrhosis (67.95 ± 34.8 vs. 45.05 ± 25.9 nM min⁻¹ ; P = 0.016) especially in patients with INRs between 1.21 and 2.0. Both the ETP with Protac(®) and the ETP ratio were increased in cirrhosis (mean 1074 ± 461.4 vs. 818 ± 357.9 nM min, P = 0.004 and 0.80 ± 0.21 vs. 0.44 ± 0.15, P ≤ 0.0001, respectively).

Conclusion: Despite a raised INR, TG parameters are consistent with a hypercoagulable profile in cirrhosis-related coagulopathy. This confirms that the PT or INR should not be used to assess bleeding risk in these patients, and other parameters, such as TG, need to be explored as clinical markers of coagulopathy.

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Blood Coagulation
  • Blood Coagulation Disorders / therapy*
  • Female
  • Fibrinolytic Agents / therapeutic use
  • Fibrosis / blood*
  • Fibrosis / therapy*
  • Hemorrhage
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • International Normalized Ratio
  • Liver / pathology*
  • Male
  • Middle Aged
  • Peptides / therapeutic use
  • Protein C / chemistry*
  • Risk
  • Thrombin / chemistry*


  • Anticoagulants
  • Fibrinolytic Agents
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Protein C
  • snake venom protein C activator
  • Thrombin