Rapid Formation of Large Molecular Weight a-Polymers in Cross-Linked Fibrin

After fibrin polymerization, activated Factor XIII catalyzes the formation of intermolecular cross-links between '-ychain pairs and also among two or more a-chains to form polymers. In this report we characterize the size and heterogeneity of a-chain polymers, establish the role of high concentrations of Factor XIII in determining the extent and rate of a-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 a-chain polymers with M, 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 a-polymer chain. In plasma containing no platelets, a-polymer formation was incomplete with residual a-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 a-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.