Resistance to Thrombomodulin but Not to Activated Protein C in Cirrhotic Patients

• Published in: Blood 2014-12, Vol.124 (21), p.2839-2839
• Main Authors: Sinegre, Thomas, Abergel, Armand, Duron, Cedric, Berger, Marc G, Lebreton, Aurélien
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.2839.2839

Introduction: Cirrhotic patients have an impairment of haemostasis. They are exposed to both thrombotic and bleeding events. Global coagulation tests as thrombin generation assays (TGA) could be informative to evaluate the coagulation step in this context. When the protein C (PC) pathway is sensibilised using thrombomodulin (TM), a « resistance » to the PC pathway appears, increasing with the severity of the hepatopathy. Nevertheless, patients with cirrhosis have a decrease protein C level which is probably involved in this « resistance ». The aim of this study was to compare the TGA with thrombomodulin or activated PC (aPC) to by-pass the PC defect. Materials and Methods: Patients prospectively included were confirmed cirrhotic patients (prothrombin time 20 kPa and/or histology and/or association of portal hypertension and liver failure). Patients were exclusively male, free of hepatocellular carcinoma and were not anticoagulated. Patients with on-going infection or inflammatory complication were excluded. None of them had a thromboembolic event or a familial history of thromboembolism. TGA were performed in the presence/absence of TM and in the presence/absence of aPC, with previously determined concentrations inhibiting 50% of endogeneous thrombin potential (ETP) of healthy plasmas. Results were expressed as ratios with/without TM or with/without aPC. Statistical analysis was based on Kruskal-Wallis test and Dunn’s post test. All tests were performed in triplicate. The study met all ethical autorizations. Results: We enrolled 15 Child-Pugh A, patients 11 Child-Pugh B, 10 Child-Pugh C and 14 healthy controls. Comparatively to controls, PC, protein S (PS) and FVIII levels were significantly decreased in cirrhotic patients. ETP ratio with TM were statistically different between controls vs Child-Pugh B (p