Flaujeac Trait: Deficiency of Human HMW Kininogen

The propositus, a 50 year-old woman of French Caucasian extraction, was the product of a consanguineous marriage. Her plasma, obtained at the time of a surgical procedure, exhibited prolonged whole blood clotting time and prolonged activated PTT (618 sec); the one-stage prothrombin time was normal. Her plasma contained normal amounts of coagulation factors XII, XI, IX, VIII, VII, X, V, II, I and Fletcher factor. Full correction was obtained upon mixing with normal plasma, excluding a circulating anticoagulant. The defect of the propositus, surname Flaujeac, was designated Flaujeac Trait. Three of the patient’s children had reduced amounts of the factor (23%, 27%, 30%) while a fourth child was at the lower limit of normal (55%).Flaujeac trait plasma was also found to have prolonged euglobulin lysis (194 min), failure of kaolin-activated kinin formation or generation of the permeability globulin PF/dil. Each of these deficits was corrected by addition of a factor separable from Hageman factor or Fletcher factor (prekallikrein). The Flaujeac factor was identified as a heat stable, α-globulin which eluted from Sephadex G-200 corresponding to a MW of 170,000. The factor corresponded exactly with fractions containing HMW kininogen. The half-life in plasma following transfusion was 6.5 days. Kininogen antigen was markedly reduced in Flaujeac plasma, only some partially cross-reacting material remained. Antibody to kininogen depleted the factor from normal plasma.The intrinsic coagulation, fibrinolytic and kinin-forming pathways and the formation of PF/dil are dependent upon plasma HMW kininogen.