Factor XIIIa Cross-Linking of the Marburg Fibrin:
Formation of
m·
n-Heteromultimers and
the -Chain-Linked Albumin· Complex, and Disturbed
Protofibril Assembly Resulting in Acquisition of Plasmin Resistance
Relevant to Thrombophila
Teruko Sugo,
Chizuko Nakamikawa,
Mikihiro Takebe,
Isao Kohno,
Rudorf Egbring, and
Michio Matsuda
From the Division of Hemostasis and Thrombosis Research, Institute of
Hematology, Jichi Medical School, Tochigi, Japan; and the Medical
University Clinic Marburg/Lahn, Marburg, Germany.
The truncated A
-chain of fibrinogen Marburg is partly linked with
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-and 
-chains) and albumin, 0.33 mol of albumin was
estimated to be linked to 1 mol of the Marburg fibrinogen. When the
Marburg fibrinogen was clotted with thrombin-factor
XIIIa-Ca2+, various mn
heteromultimers were produced, and part of the albumin was cross-linked
to the -chain. Acid-solubilized Marburg fibrin monomer failed to
form large aggregates that could be detected by monitoring turbidity at
A350, but it was able to enhance tissue-type plasminogen-activator-catalyzed plasmin generation, though not as
avidly as the normal control, indicating that the double-stranded protofibrils had, to some extent, been constructed. This idea seems to
be supported by normal factor XIIIa-catalyzed cross-linking of the
fibrin -chains. However, the cross-linked Marburg fibrin, being
apparently fragile and translucent, was highly resistant against
plasmin, and its subunit components were considerably retained for 48 hours as noted by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis. Although the exact mechanisms are still unclear, the
albumin-incorporated factor XIIIa-cross-linked Marburg fibrin seems to
have undergone a critical structural alteration(s) to acquire
resistance against plasmin. This aquisition of plasmin resistance may
be contributed to the postoperative pelvic vein thrombosis and
recurrent pulmonary embolisms in the patient after caesarian section
for her first delivery at the age of 20 years.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3282-3288
© 1998 by The American Society of Hematology.
