Dextran‐Induced Anaphylactoid Reaction in Man: Altered Reactivity of High Molecular Weight Kininogen

Abstract

Normal levels of factor XI1 and of high and low molecular weight kininogens (HMWK and LMWK) were registered in plasma specimens from 5 individuals who had developed anaphylactoid reactions upon injection of dextran during surgery (dextran reactors, DR). Factor XI1 was assayed as prekallikrein activator (PKA) activated with kaolin at 0 ' . and kininogen fractions were estimated through the release of kinin caused by plasma kallikrein or hog pancreas kallikrein (HPK). Subnormal levels of factor XI1 apparently present in plasma from one DR, and after affinity chromatography on a lysine-Sepharose column also in plasma from another DR, were normalized by addition of plasma deficient in factor XI1 or by addition of purified HMWK.Treatment of plasma from DR with acetone ( 2 5 % v/v) induced a conversion of HMWK into a state which was non-functional as a cofactor in the surface-dependent activation of factor XII, and the passage of plasma from DR through a lysine-Sepharose column altered the HMWK present to a substance that released kinin only very slowly by incubation with HPK. It is concluded that the treatments mentioned will favour the activation in plasma from DR of a factor that will cause the conversion of HMWK. Previous experiments with rat plasma demonstrated that plasmin and also a plasmin-like factor without affinity for lysine-Sepharose were able to destroy the capacity of HMWK to function as a cofactor in the surface-dependent activation of factor XII, without a corresponding release of kinin.

Activation of Factor XII in Human Plasma: Protection by Benzamidine of the Cofactor Function of High Molecular Weight Kininogen

“…Nevertheless a considerably lower extent of activation of factor XI1 to factor XII, was registered when citrated plasma was assayed, as compared to citrated plasma with benzamidine (table 1). The extent of activation of factor XI1 in normal, citrated plasma corresponds roughly to that registered in a previous work (Briseid & Briseid 1980). The addition of benzamidine and then purified HM,K t o acetone-treated citrated plasma prior to kaolin incubation increased the extent of activation of factor XI1 to PKA (not shown in the paper).…”

“…Level of functionaIIy active HM,K in plasma specimens from healthy individuals. The mean value for HM,K obtained in plasma specimens from healthy men (0.81 pg/ml plasma as bradykinin equivalents) was well within the range given in the most recent literature (about 0.70 to 1.00 pg/ml plasma), and obtained by different methods (Kleniewski & Donaldson 1977;Uchida et al 1977;Bouma et al 1980;Briseid & Briseid 1980 ; Proud et a/. 1980).…”

“…It could also indicate that the lower estimates of HM,K in individual plasma specimens (table 5 ) could reflect a high level of the unknown protease, and not only the lower range of the normal HM,K concentrations in vivo. Experiments carried out by Briseid & Briseid (1980) with plasma specimens from healthy men and from individuals with a history of anaphylactoid reaction to dextran support the assumption of a secondary loss of cofactor-active HM,K. The authors mentioned concluded from their experiments that the significantly lowered cofactor capacity of HM,K in plasma from the patients was probably not genuinely present, but developed during the assay procedure.…”

“…The latest publications show that the normal concentration of HM,K seems to be in the range 0.70-1 .OO pg per ml plasma as bradykinin equivalents (bioassay: Uchida eta/. 1977;Briseid & Briseid 1980;Proud et al 1980;immunoassay: Kleniewski & Donaldson 1977;Bouma et al 1980;Proud et al 1980). The capacity of HMrK to facilitate the activation of factor XI1 by kallikrein is well established, and assays of HMrK as cofactor in coagulation tests have been widely used.…”

“…In the present work the kinin-free HM,K present in acetone-treated plasma was assayed as cofactor in kallikrein-induced activation of factor XI1 to prekallikrein activator (PKA). Such PKA assays were previously made in citrated plasma (Briseid & Briseid 1980). In the present work the addition of benzamidine to citrated plasma caused a significant increase in the yield of functionally active HM,K.…”