Effect of bovine high molecular weight kininogen and its fragments on fitzgerald trait plasma

Abstract

Fitzgerald trait, a deficiency of high molecular weight (HMW) kininogen, is characterized by a prolongation of both the activated partial thromboplastin time (aPTT) and of the kaolin-activated euglobulin lysis time. To study the role of HMW kininogen in coagulation and fibrinolysis, highly purified bovine HMW kininogen, kinin-free HMW kininogen, a histidine-rich fragment of HMW kininogen, and low molecular weight (LMW) kininogen were obtained. The effects of these proteins on the aPTT and kaolin-activated euglobulin lysis time of Fitzgerald trait plasma were studied. It was found that whole bovine plasma and HMW kininogen had identical capacities to partially correct the prolonged aPTT. Kinin-free HMW kininogen had only 30% of the correcting capacity of intact HMW kininogen. LMW kininogen had no effect on the aPTT of Fitzgerald plasma. The histidine-rich fragment prolonged the aPTT of Fitzgerald plasma and of normal human plasma without affecting the one-stage prothrombin time. HMW kininogen also corrected the kaolin-activated euglobulin lysis time of Fitzgerald plasma. Kinin-free HMW kininogen and LMW kininogen had weak capacities to correct the Fitzgerald kaolin-activated euglobulin lysis time. The histidine-rich fragment significantly prolonged the kaolin-activated euglobulin lysis time of Fitzgerald and normal plasmas. The histidine-rich fragment appears to inhibit the activation of Hageman factor (Factor XII) by kaolin or ellagic acid. Our data suggest that intact bovine HMW kininogen corrects the deficiency of Fitzgerald trait plasma; but the hydrolysis of HMW kininogen by plasma kallikrein yields peptides with decreased correcting activity, and at least one with inhibitory activity in contact-mediated coagulation and fibrinolysis.