Oversulfated heparin by-products induce thrombin generation in human plasmas through contact system activation

Yi Qian, Jing Pan, Xiaodong Zhou, Dennis E. Hourcade, M. Kathryn Liszewski, John P. Atkinson, Hong Lu, Lijuan Zhang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Thrombin generation is thought to be mediated predominantly by the tissue factor or "extrinsic" coagulation pathway. An alternate pathway to thrombin generation (the "intrinsic" pathway or contact system) has been observed when blood or plasma comes in contact with artificial surfaces. Here we present evidence for a new route to thrombin formation that begins with the activation of the contact system protein prekallikrein by oversulfated heparin (OS-HB). Kallikrein, instead of activated factor X, cleaves prothrombin to form thrombin. Thrombin then cleaves fibrinogen to form fibrin clots. Moreover, we show that OS-HB by-products induce kallikrein- and thrombin-like activities in normal human plasma and in human plasma devoid of coagulation factor X or downstream contact system components factor IX or factor XI. Oversulfated heparin by-product-induced thrombin generation may have had a role in the adverse reactions associated with the recent clinical use of contaminated heparin.

Original languageEnglish (US)
Pages (from-to)244-250
Number of pages7
JournalClinical and Applied Thrombosis/Hemostasis
Volume16
Issue number3
DOIs
StatePublished - Jun 2010

Keywords

  • Contact system
  • Contaminated heparin
  • Kallikrein
  • Thrombin

ASJC Scopus subject areas

  • Hematology

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