Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests
The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear, partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo.
Conventional coagulation tests include prothrombin time and activated partial thromboplastin time.
Dr Tripodi and colleagues from Italy propose that these are inadequate to explore the physiological mechanism regulating thrombin, because they do not allow full activation of the main anticoagulant factor, protein C, whose levels are considerably reduced in cirrhosis.
The researchers used a thrombin generation test to investigate the coagulation function in patients with cirrhosis.
|Reduced procoagulant factors in patients with cirrhosis is compensated by a reduction of anticoagulant factors.|
The team showed that thrombin generation without thrombomodulin was impaired, which is consistent with the reduced levels of procoagulant factors typically found in cirrhosis.
However, when the test was modified by adding thrombomodulin, the protein C activator operating in vivo, patients generated as much thrombin as controls.
Hence, the team observed that the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, leaving the coagulation balance unaltered.
The researchers found these results helped clarify the pathophysiology of hemostasis in cirrhosis.
In addition, the researchers suggested that bleeding is mainly due to the presence of hemodynamic alterations.
The team also noted that conventional coagulation tests are unlikely to reflect the coagulation status of these patients.
Dr Tripodi concluded, “Generation of thrombin is normal in cirrhosis.”
“For a clinical validation of these findings, a prospective clinical trial is warranted where the results of thrombin generation in the presence of thrombomodulin are related to the occurrence of bleeding.”