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MECHANISMS FOR HAGEMAN FACTOR ACTIVATION AND ROLE OF HMW KININOGEN AS A COAGULATION COFACTOR
Author(s) -
Kaplan Allen P.,
Silverberg Michael,
Dunn Joseph T.,
Miller Geraldine
Publication year - 1981
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1981.tb29738.x
Subject(s) - factor xii , cofactor , coagulation , chemistry , high molecular weight kininogen , prekallikrein , kininogen , biochemistry , kallikrein , medicine , enzyme
Our present concept of the initiating reactions of the intrinsic coagulation pathway is outlined in Figure 5. Although we remain unsure of the etiology shown in Figures 3 and 4, the major function of HMW kininogen is to bind prekallikrein and factor XI in plasma and attach them to surfaces in a conformation that allows activation by HFa. The HMW kininogen--dependent augmentation of the binding of prekallikrein and factor XI to the surface that is seen in plasma (but not buffer systems) would appear to be of lesser importance. Once activated, however, dissociation of kallikrein from the surface allows it to attack adjacent Hageman factor molecules on the same or other particles; this reaction appears to be more rapid than the rate of Hageman factor autoactivation. Thus, the rapid burst of HFa formation seen in normal plasma is kallikrein dependent. It is also dependent upon HMW kininogen, but this appears to be an indirect relationship. The HMW kininogen augments the amount of prekallikrein bound, allows activation to kallikrein, and is needed for kallikrein dissociation from the surface. These three effects all yield a marked increase in the effective ratio of kallikrein/Hageman factor at the surface-fluid interface, and this may be the condition required for rapid HFa formation.