Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Jun Wan, Lara N. Roberts, Wasiliki Hendrix, Joke Konings, Tsai-Wing Ow, Liane Rabinowich, Omar Barbouti, Bas De Laat, Roopen Arya, Vishal C. Patel, Mark Roest, Ton Lisman, William Bernal

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Abstract

Background and Aims Patients with cirrhosis have a rebalanced hemostasis, often with normal or elevated thrombin-generating (TG) capacity in plasma. Whole blood (WB) TG allows faster determination and, importantly, includes the influence of all circulating blood cells. We aimed to study the TG profile of patients with cirrhosis in WB and in platelet poor plasma.

Methods Thrombin-generating capacity in WB and plasma were assessed with a near-patient WB-TG assay and the calibrated automated thrombinography assay, respectively. TG assays were tested in presence and absence of thrombomodulin. Conventional coagulation tests were also performed.

Results Thirty-four patients with cirrhosis and twenty-two controls were analyzed. Compared with controls, patients had substantially deranged results in conventional coagulation tests. Comparable WB-TG capacity (endogenous thrombin potential until peak, ETPp) but significantly lower peak thrombin were found in patients, and these results persisted when thrombomodulin was present. TG of the patients was more resistant to thrombomodulin than controls in both WB and plasma, although the inhibitory effect of thrombomodulin was drastically weaker in WB than in plasma. The peak of WB-TG in patients correlated moderately with their hematocrit and platelet count. Significant correlations were found between TG results in WB and plasma.

Conclusions The WB-TG assay shows a normal to hypocoagulable state in patients with cirrhosis with a decreased anticoagulant activity of TM compared to plasma-TG. The clinical value of this assay needs further validation.

Original languageEnglish
Pages (from-to)834-843
Number of pages10
JournalJOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume18
Issue number4
DOIs
Publication statusPublished - Apr-2020

Keywords

  • chronic liver disease
  • coagulation
  • thrombin generation
  • bleeding
  • thrombosis
  • ACUTE LIVER-INJURY
  • PROCOAGULANT IMBALANCE
  • HYPERCOAGULABLE STATE
  • ACUTE DECOMPENSATION
  • PROTEIN-C
  • DISEASE
  • THROMBOMODULIN
  • COAGULATION
  • HEMOSTASIS
  • COAGULOPATHY

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