Prekallikrein Deficiency in Man

Abstract

Blood plasma obtained from an individual with abnormal thromboplastin formation, due to deficiency of Fletcher factor, was fully corrected by 2% of normal, Hageman factor- or PTA-deficient plasma. It was also reconstituted by addition of highly purified human or rabbit prekallikrein. The plasma failed to generate kinin upon exposure to kaolin, a defect which was also corrected by addition of prekallikrein. Prekallikrein antigen was not detectable in this plasma. Fletcher factor-deficient plasma did not support the normal generation of PF/dil when dilute plasma was incubated in glass vessels and injected intracutaneously. Small quantities of Fletcher factor-deficient or Hageman factor-deficient plasma corrected the ability of the other to generate PF/dil. The formation of plasmin in dilute, acidified plasma incubated with kaolin was also abnormal in Fletcher factor-deficient plasma. Plasmin generation was normalized by addition of prekallikrein or small quantities of Hageman factor-deficient plasma. The data support the identity of Fletcher factor and prekallikrein.

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

“…In this regard it is important to note the relative potency of each enzyme required to cleave 10% of available HF molecules as calculated from the data in Figs. 1-3 125I-HF are severely retarded but not absent in prekallikrein-deficient plasma (7,8,20). Given the high sensitivity of surface-bound HF to cleavage of plasmin (Table 1), it is tempting to speculate that a secondary pathway could involve plasmin.…”

“…Hence, soluble kallikrein, which is potent in the cleavage of surfacebound HF, is rapidly generated and readily available in plasma during contact activation. Fifth, the correction of the coagulation defect of prekallikrein-deficient plasma requires the addition of enzymatically active kallikrein as well as kaolin (8,34,35). Thus, reciprocal proteolytic activation of HF and prekallikrein (20,21,32,35) probably represents the major mechanism responsible for contact activation of HF.…”

“…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).…”

Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways.

“…In contrast, Factor XI deficiency in man results in a mild bleeding tendency (8) with a defect in the rate of thrombin formation but no abnormalit) in kallikrein or plasmin formation. Individuals lacking prekallikrein (9) resemble those with Factor XII deficiency and display, in addition to the expected absence of kinin formation, a diminished rate of surface-activated coagulation and fibrinolysis (10,11). These latter abnormalities are attributed to a feedback requirement in which kallikrein activates Factor XII to an enzvme that can then act upon each substrate (11)(12)(13).…”

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.

“…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).…”