Hypercoagulability in Cirrhotic Patients; Impact of Acquired Protein C Deficiency and Factor VIII Increase in Low Sensitivity to Thrombomodulin

• Published in: Blood 2016-12, Vol.128 (22), p.1420-1420
• Main Authors: Sinegre, Thomas, Duron, Cedric, Berger, Marc G., Abergel, Armand, Lebreton, Aurelien
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.1420.1420

Context: Cirrhosis impacts all the steps of haemostasis including coagulation. Levels of both inhibitors (including protein C (PC)) and prococagulants factors are decreased excepted factor VIII (FVIII) who is increased. Cirrhotic patients are exposed to thromboembolic diseases and cirrhosis induced hypercoagulability is a major determinant of this thrombotic process. A procoagulant state in cirrhotic patients has been demonstrated using modified thrombin generation assays (TGA) with thrombomodulin (TM), a cofactor for PC activation. With such assays, a low sensitivity to the action of TM has been highlighted in the cirrhotic population, increasing with the severity assessed by the Child-Pugh score. Studies showed that PC deficiency is one of the main determinants of this procoagulant state but the implication of the increased FVIII levels has not been yet accurately evaluated. The aim of this study was to investigate the impact of in vitro normalization of FVIII and PC levels on the procoagulant imbalance in cirrhotic patients using TGA in the presence of TM to precisely determine their role in the cirrhosis induced procoagulant state. Method: One hundred and six patients and 35 healthy controls were prospectively included in this study. Patients were confirmed cirrhotic patients, free of hepatocellular carcinoma and were not anticoagulated. TGA were performed using the calibrated automated thrombinography method in platelet poor plasma using 5 pM tissue factor, 4 nM TM. Plasma were tested before/after normalization of PC levels by in vitro addition of PC and before/after normalization of FVIII levels by the use of human anti-FVIII C2 domain monoclonal antibody (ESH8). All ethical requirements were obtained. Groups were compared using ANOVA, or the Kruskal-Wallis test when the ANOVA conditions were not met followed by the appropriate multiple comparisons post-hoc tests. Results are expressed as median (Q1 - Q3). Results:Among cirrhotic patients 68 were Child-Pugh A, 21 Child-Pugh B and 17 Child-Pugh C). TGA performed with TM show a gradually increased of endogenous thrombin potential (ETP) from healthy controls to Child-Pugh C patients with respectively 508 nM.min (410-725) and 1071 nM.min (701-1232) (p0.05). Modified TGA with TM performed before and after