FACTOR XIIIA CROSS-LINKING OF THE MARBURG FIBRIN - FORMATION OF ALPHA(M)CENTER-DOT-GAMMA(N)-HETEROMULTIMERS AND THE ALPHA-CHAIN-LINKED ALBUMIN-CENTER-DOT-GAMMA COMPLEX, AND DISTURBED PROTOFIBRIL ASSEMBLY RESULTING IN ACQUISITION OF PLASMIN RESISTANCE RELEVANT TO THROMBOPHILA

The truncated A alpha-chain of fibrinogen Marburg is partly linked wit h albumin by a disulfide bond. Based on the recovery of the first six amino acid residues assigned to the subunit polypeptides of fibrinogen (the A alpha-and gamma-chains) and albumin, 0.33 mol of albumin was e stimated to be linked to 1 mol of the Marburg fibrinogen. When the Mar burg fibrinogen was clotted with thrombin-factor XIIIa-Ca2+, various a lpha(m) gamma(n) heteromultimers were produced, and part of the albumi n was cross-linked to the gamma-chain. Acid-solubilized Marburg fibrin monomer failed to form large aggregates that could be detected by mon itoring turbidity at A350, but it was able to enhance tissue-type plas minogen-activator-catalyzed plasmin generation, though not as avidly a s the normal control, indicating that the double-stranded protofibrils had, to some extent, been constructed. This idea seems to be supporte d by normal factor XIIIa-catalyzed cross-linking of the fibrin gamma-c hains, However, the cross-linked Marburg fibrin, being apparently frag ile and translucent, was highly resistant against plasmin, and its sub unit components were considerably retained for 48 hours as noted by so dium dodecyl sulfate-polyacrylamide gel electrophoresis, Although the exact mechanisms are still unclear, the albumin-incorporated factor XI IIa-cross-linked Marburg fibrin seems to have undergone a critical str uctural alteration(s) to acquire resistance against plasmin. This aqui sition of plasmin resistance may be contributed to the postoperative p elvic vein thrombosis and recurrent pulmonary embolisms in the patient after caesarian section for her first delivery at the age of 20 years , (C) 1998 by The American Society of Hematology.