Rapid formation of large molecular weight alpha-polymers in cross-linked fibrin induced by high factor XIII concentrations. Role of platelet factor XIII.

After fibrin polymerization, activated Factor XIII catalyzes the formation of intermolecular cross-links between gamma-chain pairs and also among two or more alpha-chains to form polymers. In this report we characterize the size and heterogeneity of alpha-chain polymers, establish the role of high concentrations of Factor XIII in determining the extent and rate of alpha-polymer formation, and also provide evidence that the Factor XIII required can be provided by platelets. Fibrin prepared from purified fibrinogen or platelet-deficient plasma contained a series of cross-linked alpha-chain polymers with Mr from 140,000 to 770,000 with a mean Mr difference of 32,000 consistent with a staggered, overlapping addition of monomers to the growing alpha-polymer chain. In plasma containing no platelets, alpha-polymer formation was incomplete with residual alpha-monomer remaining, but higher platelet counts facilitated more rapid cross-linking into larger polymers. Purified Factor XIII was equally effective as platelets in facilitating cross-linking. We conclude that cross-linked alpha-polymer chains are heterogeneous in size reaching a molecular weight of several million and that high concentrations of Factor XIII as provided by platelets are required for maximum cross-linking.