Plasma hypercoagulability in the presence of thrombomodulin but not of activated protein C in patients with cirrhosis

Background and Aims Cirrhosis significantly changes all hemostasis steps. Recent studies suggest that cirrhosis is associated with a coagulopathy leading to a hypercoagulable state. The underlying mechanisms are not fully understood, but protein C deficiency is probably a major determinant of this p...

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Bibliographic Details
Published in:European journal of soil science 2017-04, Vol.32 (4), p.916-924
Main Authors: Lebreton, Aurélien, Sinegre, Thomas, Pereira, Bruno, Lamblin, Géraldine, Duron, Cédric, Abergel, Armand
Format: Article
Language:English
Subjects:
Activated protein C
Adult
Aged
Blood Coagulation
Cirrhosis
Coagulation
Female
Food and Nutrition
Hemostasis
Hip joint
Human health and pathology
Humans
hypercoagulability
Hépatology and Gastroenterology
Life Sciences
Liver cirrhosis
Liver Cirrhosis - blood
Liver Cirrhosis - complications
Male
Middle Aged
Phospholipids
Prospective Studies
Protein C
Protein C - metabolism
Protein C Deficiency - complications
Protein deficiency
Protein S
Proteins
Severity of Illness Index
Thrombin
thrombin generation
Thrombomodulin
Thrombomodulin - metabolism
Thrombophilia - etiology
Tissue factor
Young Adult
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Summary:Background and Aims Cirrhosis significantly changes all hemostasis steps. Recent studies suggest that cirrhosis is associated with a coagulopathy leading to a hypercoagulable state. The underlying mechanisms are not fully understood, but protein C deficiency is probably a major determinant of this phenotype. The aim of this study was to compare the results of thrombin generation assays performed with addition of thrombomodulin or activated protein C to assess the effect of by‐passing the protein C activation step in cirrhotic patients and healthy controls. Methods Fifty‐eight patients with cirrhosis and 26 healthy controls were prospectively included in this study. Thrombin generation was determined in platelet‐poor plasma using 5 pM of tissue factor and 4 nM of phospholipids, without and with external addition of 1 nM thrombomodulin or 4 nM activated protein C. All results were normalized with the values of a pool of normal plasma samples to limit inter‐plate variability. Results When thrombin generation assays were performed in the presence of thrombomodulin, endogenous thrombin potential (ETP) and ETP with/ETP without TM ratio were significantly higher in cirrhotic patients than in healthy controls (P 
ISSN:0815-9319
1351-0754
1440-1746
1365-2389
DOI:10.1111/jgh.13493