FIBRINOGEN CLARO - ANOTHER DYSFUNCTIONAL FIBRINOGEN VARIANT WITH GAMMA-275-ARGININE-]HISTIDINE SUBSTITUTION

Dysfunctional fibrinogen variants have been discovered by prolongation of thrombin and reptilase clotting times and a discrepancy of the fun ctionally and immunologically determined fibrinogen concentration. Mor e than 250 variants have been described (1). Majority of the abnormal fibrinogen variants have a structural defect near or at the thrombin c leavage site in the Aa-chain (2,3). Removal of fibrinopeptide A is req uired to expose the amino-terminal polymerization site (4,5). Most mol ecular defects in abnormal fibrinogen variants with normal fibrinopept ide A release but impaired fibrin monomer polymerization have been loc alized within residues gamma 275 to gamma 375 (1) containing the putat ive carboxy terminal polymerization site gamma 337-379 (6,7). In the p resent report we describe another congenitally abnormal fibrinogen tha t was found in a 42-year-old asymptomatic woman and her son. A single amino acid substitution gamma 275 Arg --> His was found in this dysfun ctional fibrinogen variant.