The Polymerization of Fibrin Prepared from Fibrinogen Haifa (γ275Arg→His)

Publisher Website
Google Scholar
Abstract
Fibrinogen Haifa is a congenital heterozygous fibinogen variant (γ275 Arg→His) characterized by prolonged thrombin and reptilase times and normal fibrinopeptide (FPA, FPB) release. We compared the polymerization rate (by turbidity measurements at 350 nm) and the ultrastructure of Haifa α-, β-, and α, β-fibrin with that of normal. Haifa α, β-fibrin polymerized less rapidly than did normal and formed a highly branched matrix with a smaller mean fiber diameter; this network closely resembled that of normal α, β-fibrin with EDTA added. In the presence of CaCl2 (1 to 10 mM), Haifa α, β-fibrin polymerized more rapidly than in buffer alone and possessed a matrix structure closely resembling that of normal fibrin. From these observations it appears that the functional defect in Haifa fibrin can be related to the inability of the abnormal molecule to effectively utilize available calcium. The polymerization profile of Haifa α-fibrin differed only modestly from that of normal α-fibrin, whereas that of Haifa β-fibrin was markedly impaired. This finding plus similarities in the ultrastructure of Haifa and normal α-fibrin specimens suggests that the defective γ chain structure of Haifa fibrinogen results in greater impairment of the carboxy terminal “b” polymerization domain reacting with the site exposed by cleavage of FPB (“B” site) than it does that of the carboxy terminal “a” domain reacting with the site exposed by cleavage of FPA (“A” site). Whether this effect is due to absolute differences in the degree of impairment of these two types of polymerization sites, or whether proper utilization of the “B” to “b” site is dependent upon participation of the “A” to “a” site remains to be determined.