Fibrinogen Milano. VI: A heterozygous dysfibrinogenemia (A alpha 16 Arg----His) with bleeding tendency.

Congenital heterozygous dysfibrinogenemia was diagnosed in a young woman with bleeding tendency. 3 other asymptomatic members of her family (mother and the 2 sisters) had abnormal fibrinogen. The proposita's plasma exhibited prolonged thrombin and reptilase times. Plasma fibrinogen concentration determined by functional assay was 0.3 g/l, whereas immunologic assay revealed normal fibrinogen levels. Turbidity curves, representing the rate of thrombin-induced fibrin formation, were markedly delayed both in the presence and absence of Ca2+. Isoelectric focusing and SDS electrophoresis of reduced fibrinogen showed normal charge and size of the subunit chains. Release of fibrinopeptide B by thrombin was normal, whereas HPLC elution diagrams of fibrinopeptide A showed an abnormal peak A* with a slightly shorter retention time than the normal fibrinopeptide A. The amino acid analysis showed that the arginine in peak A* is replaced by histidine (A alpha 16 Arg----His).