Parallel procoagulant and anticoagulant pathways for high molecular weight kininogen coagulant function.
High molecular weight kininogen (HK) or its procoagulant light-chain but not the heavy chain potentiated the heparin enhancement of antithrombin III inactivation of plasma kallikrein and factor XIa from 10-50-fold to approximately 1000-fold at I 0.15, pH 7.4, 25 degrees C. This potentiation resulted in antithrombin becoming a predominant inhibitor of kallikrein and factor XIa in heparinized normal but not HK-deficient plasmas. The heparin chain-length and salt dependence of this potentiation suggested an anticoagulant action of HK analogous to its procoagulant action.
Olson
S T
ST
Henry Ford Hospital, Detroit, MI 48202.
Sheffer
R
R
Shore
J D
JD
D000990:Antithrombin III / Q000494:pharmacology; D001665:Binding Sites; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D015945:Factor XIa / Q000037:antagonists & inhibitors; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007700:Kinetics; D007704:Kininogens / Q000494:pharmacology / Q000502:physiology*; D008954:Models, Biological
D007704:Kininogens; D000990:Antithrombin III; D006493:Heparin; D007610:Kallikreins; D015945:Factor XIa