A gamma methionine-310 to threonine substitution and consequent N-glycosylation at gamma asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi.

In an abnormal fibrinogen with severely impaired polymerization of fibrin monomers, we identified a methionine-to-threonine substitution at position 310 of the gamma chain. Furthermore, asparagine at position 308 was found to be N-glycosylated due to a newly formed consensus sequence, asparagine(308)-glycine(309)-threonine(310). The two structural defects in the mutant gamma chain may well perturb the conformation required for fibrin monomer polymerization that is specifically assigned to the D domain of fibrinogen. This alteration also seems to affect the intermolecular gamma chain cross-linking of fibrin and fibrinogen, although the amine acceptor gamma glutamine-398 was found to function normally. These functional abnormalities may well be related to posttraumatic hemorrhage as observed in a 33-yr-old man with moderate hemorrhagic diathesis related to injuries since his early adolescence. The structure of the extra carbohydrate moiety attached to asparagine-308 was found to be identical with those derived from the normal B beta and gamma chains as evidenced by HPLC.

Congenital deficiency of alpha 2-plasmin inhibitor in three sisters.

3 young Japanese sisters with congenital alpha 2-plasmin inhibitor (alpha 2-PI) deficiency are reported. They have mild umbilical bleeding and/or repeated prolonged bleeding after minor trauma, but rarely spontaneous bleedings. The most characteristic hemostatic findings were shortened whole blood clot lysis time and euglobulin lysis time. Activities of all hemostatic factors except alpha 2-PI were within normal range. Both functional and immunological absence of alpha 2-PI were found in the plasma, and this failure to detect alpha 2-PI was not corrected by the addition of the patient's plasma of the first described case of alpha 2-PI deficiency. Clinical and laboratory data revealed that these patients were probably homozygous for alpha 2-PI deficiency and born of heterozygous parents, but not of consanguineous ones. Bleeding episodes due to deficiency of alpha 2-PI in these patients were well controlled by an antifibrinolytic agent, tranexamic acid.