RGD Reference Report - Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. - Rat Genome Database

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Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests.

Authors: Tripodi, Armando  Salerno, Francesco  Chantarangkul, Veena  Clerici, Marigrazia  Cazzaniga, Massimo  Primignani, Massimo  Mannuccio Mannucci, Pier 
Citation: Tripodi A, etal., Hepatology. 2005 Mar;41(3):553-8. doi: 10.1002/hep.20569.
RGD ID: 14985236
Pubmed: PMID:15726661   (View Abstract at PubMed)
DOI: DOI:10.1002/hep.20569   (Journal Full-text)

The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear. This is partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time 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. We used a thrombin generation test to investigate the coagulation function in patients with cirrhosis. Thrombin generation measured 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 (i.e., the protein C activator operating in vivo), patients generated as much thrombin as controls. Hence, the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, thus leaving the coagulation balance unaltered. These findings help clarify the pathophysiology of hemostasis in cirrhosis, suggesting that bleeding is mainly due to the presence of hemodynamic alterations and that conventional coagulation tests are unlikely to reflect the coagulation status of these patients. In conclusion, 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis severityISOF2 (Homo sapiens)14985236; 14985236protein:decreased activity:plasma (human)RGD 
liver cirrhosis severityIEP 14985236protein:decreased activity:plasma (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
F2  (coagulation factor II, thrombin)

Genes (Mus musculus)
F2  (coagulation factor II)

Genes (Homo sapiens)
F2  (coagulation factor II, thrombin)

Objects referenced in this article
Gene NR1H4 nuclear receptor subfamily 1 group H member 4 Homo sapiens
Gene Nr1h4 nuclear receptor subfamily 1, group H, member 4 Mus musculus
Gene Nr1h4 nuclear receptor subfamily 1, group H, member 4 Rattus norvegicus

Additional Information