Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis

Armando Tripodi, Massimo Primignani, Laura Lemma, Veena Chantarangkul, Pier Mannuccio Mannucci

Research output: Contribution to journalArticlepeer-review


Background & Aims Cirrhosis is associated with a plasmatic procoagulant imbalance, detected in vitro by thrombin generation tests performed in the presence vs. absence of such activators of protein C as thrombomodulin or Protac®. This imbalance is thought to be due to decreased protein C and increased factor VIII, but this has never been directly demonstrated. To test this hypothesis we analyzed plasma from 50 patients with cirrhosis before and after in vitro addition of purified protein C meant to restore normal levels. Methods Results for two thrombin generation assays were expressed as ratios of endogenous thrombin potential (ETP) with-to-without thrombomodulin or as Protac®-induced coagulation inhibition (PICI%). By definition, high ETP ratios or low PICI% reflect a resistance to the anticoagulant action of thrombomodulin or Protac®, respectively, and can be taken as indexes of in vitro procoagulant imbalance. Results The median (range) protein C level before addition was 40% (4-101%) and increased to 156% (110-305) after addition (p

Original languageEnglish
Pages (from-to)265-270
Number of pages6
JournalJournal of Hepatology
Issue number2
Publication statusPublished - Aug 2013


  • Factor VIII
  • Protac®
  • Thrombin generation
  • Thrombomodulin

ASJC Scopus subject areas

  • Hepatology


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