1. Oversulfated heparin by-products induce thrombin generation in human plasmas through contact system activation.
- Author
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Yi Qian, Jing Pan, Xiaodong Zhou, Hourcade DE, Liszewski MK, Atkinson JP, Hong Lu, and Lijuan Zhang
- Subjects
- Anaphylaxis blood, Anaphylaxis chemically induced, Anticoagulants analysis, Chondroitin Sulfates adverse effects, Chondroitin Sulfates analysis, Coagulation Protein Disorders blood, Disease Outbreaks, Drug Contamination, Enzyme Activation drug effects, Fibrinogen drug effects, Heparin analysis, Humans, Kallikreins blood, Phosphatidylethanolamines pharmacology, Prekallikrein drug effects, Prekallikrein metabolism, Prothrombin metabolism, Silicon Dioxide pharmacology, Anticoagulants pharmacology, Blood Coagulation drug effects, Chondroitin Sulfates pharmacology, Heparin pharmacology, Thrombin biosynthesis
- 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.
- Published
- 2010
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