Fitzgerald Factor ( High Molecular Weight Kininogen ) Clotting Activity in Human Plasma in Health and Disease in Various Animal

Fitzgerald factor ( high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface-mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean ± SD in 42 normal adults was 0.99 ± 0.25 units/mI, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40 ± 0.09 units/mI) and of ten patients with dissem mated intravascular coagulation (0.60 ± 0.30 units/mI), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 2 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two reptilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas. F ITZGERALD TRAIT is an asymptomatic disorder of blood coagulation with a prolonged partial thromboplastin time related to the deficiency of Fitzgerald factor.’ The plasma of the index patient displayed abnormalities in other surface-mediated plasma reactions, including kinin generation, fibrinolysis, and enhancement of vascular permeability by diluted plasma (PF/Dil).2 Fitzgerald factor has been isolated from normal human plasma free of other known clotting factors.3 Five additional unrelated individuals have recently been described who have the same clotting defect as Fitzgerald trait.48 Wuepper et al.5 first identified an agent deficient in their patient’s plasmas as high molecular weight (HMW) kininogen. This finding has been confirmed in other mdividuals with the same clotting defect.3’4’6’7 Thus Fitzgerald factor appears to be identical to HMW kininogen, a component of the plasma kinin-generating