Flaujeac trait. Deficiency of human plasma kininogen.

Abstract

A B S T R A C T Flaujeac trait plasma resembled Hageman trait or Fletcher trait, in that the intrinsic coagulation pathway, plasma fibrinolytic pathway, kinin-forming system, permeability factor of dilution (PF/dil) phenomenon were abnormal. The defect in each assay was reconstituted by a factor separable from Hageman factor or Fletcher factor. This substance was an a-globulin with an approximate mol wt of 170,000. Flaujeac plasma did not release a kinin upon incubation with kallikrein and was deficient in total kininogen antigen. Antiserum to kininogen inhibited the activity of the factor in solution. Flaujeac factor was identified as a kininogen of high molecular weight (HMW-kininogen).The mean total kininogen antigen in four children of the proposita was 51% (range 34-62%) of normal. A functional coagulation assay of HMW-kininogen in the children was 34% (range 23-55%). The results were consistent with autosomal recessive inheritance.The plasma pathways of intrinsic coagulation, fibrinolysis, kinin formation, and PF/dil generation are dependent upon HMW-kininogen. We believe this is the first demonstration of biological function for a kininogen apart from its role as a substrate for kallikreins.

Abnormalities in the contact activation through factor XII in Fujiwara trait: A deficiency in both high and low molecular weight kininogens with low level of prekallikrein.

“…In this experiment, the heated plasma was diluted by saline at different ratios and added to the same volume (25 ,ul) of Fujiwara trait plasma, so that the content of HIM kininogen in the final incubation mixture would be half. This value corresponds well to the data from Wuepper et al (1975), in which addition of 12.5% of normal plasma to Flaujeac plasma showed the full correction.…”

“…In this way we estimated Fujiwara trait plasma contains about 30%, and Fitzgerald and Williams, 23-25% of normal level of prekallikrein. Reduced levels of prekallikrein in HMW kininogen deficiency were also reported by other authors (Colman et al 1975;Saito et al 1975;Wuepper et al 1975;Donaldson et al 1976). Table 5 summarizes the contents of kininogen and prekallikrein in various deficient plasmas.…”

“…Such defects reported were pre kallikrein deficiency (Fletcher factor deficiency) (Wuepper 1973), and the deficiency in high molecular weight (HMW) kininogen, like Fitzgerald trait (Saito et al 1975; Donaldson et al 1976) as well as deficiency in total kininogen, Flaujeac trait Wuepper et al 1975) and Williams trait (Colman et al 1975).…”

Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII)

“…Proteins that are known to be involved in contact activation of human plasma include Hageman factor (HF, blood coagulation Factor XII) (6), plasma prekallikrein (Fletcher factor) (7,8), coagulation Factor XI (plasma thromboplastin antecedent) (9), and high molecular weight (Mr) kininogen, which was recognized in studies.of Flaujeac trait (10), Fitzgerald trait (11,12), Williams trait (13), and "contact activation cofactor" (14).…”

The Binding and Cleavage Characteristics of Human Hageman Factor during Contact Activation

“…Again, however, it was the identification of a specific protein, in this instance HMWK (13)(14)(15)(16) (20,21). Meier et al have also reported that HMWK enhances the expression of the activity of surface-bound Hageman factor (22).…”