Defective a-Polymerization in the Conversion of Fibrinogen Baltimore to Fibrin

A B S T R A C T The subunit structure of fibrinogen Baltimore and fibrin formed from this inherited dysfibrinogenemia was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The molecular weights of the a-, fand v-chains of fibrinogen Baltimore were found to be identical to those of normal fibrinogen. Noncross-linked fibrin formed from both purified fibrinogen Baltimore as well as normal fibrinogen contained two a-monomers (al and a2). a2 was presumed to be a-monomer from which fibrinopeptide A had been released. The evolution of a2 during clotting of fibrinogen Baltimore was delayed and appeared to be quantitatively reduced when compared to normal. Crosslinked fibrin formed from fibrinogen Baltimore possessed an abnormal subunit structure. a-polymers were not generated in thrombin-induced, factor XIII-rich clots of fibrinogen Baltimore under conditions of pH and calcium concentration suitable for complete a-polymerization in normal fibrin. If clotting was carried out with calcium concentrations twice that required for normal clots or at pH 6.4, fibrin from fibrinogen Baltimore was completely cross-linked. These structural analyses of fibrin formed from fibrinogen Baltimore substantiate earlier findings that indicate a defect in the a-chain of this dysfibrinogenemia.