A functional assay suggests that heterodimers exist in two C-terminal gamma-chain dysfibrinogens: Matsumoto I and Vlissingen/Frankfurt IV

Because it contains three pairs of polypeptides, fibrinogen isolated from h eterozygous individuals is expected to be a mixture of hamodimers and heter odimers. Nevertherless, heterozygous individuals with only homodimers have been identified. We synthesized two recombinant fibrinogens with the mutati ons from fibrinogen Vlissingen/ Frankfurt IV (gamma Delta 319, 320) and Mla tsumoto I (gamma D364H), both identified in heterozygous individuals. We fo und that polymerization of these fibrinogens was undetectable in 30 min; po lymerization of a 1:1 mixture of variant and normal fibrinogen was the same as polymerization of a 1:1 mixture of buffer and normal fibrinogen; polyme rization of either plasma fibrinogen was markedly impaired when compared to the 1:1 mixture of the respective variant and normal fibrinogens. We concl ude that each plasma fibrinogen is a mix of homodimers: and heterodimers. s uch that the incorporation of heterodimers into the fibrin clot impair:, po lymerization. We suggest that incorporation of heterodimers can induce clin ical symptoms.