A New Congenital Abnormality of Human Fibrinogen

Abstract

Summary A dysfibrinogenemia (fibrinogen Bethesda II) was recognized in a Caucasian family with no history of bleeding or thrombosis. Thrombin and Reptilase times were prolonged, and there was a discrepancy between the fibrinogen levels determined by the fibrin tyrosine content and the Clauss method. Other coagulation and fibrinolytic measurements yielded normal values. The half-life of homologous and autologous 125I-fibrinogen in the propositus was approximately 20% shorter than the mean (3.70 ±0.45 days) of normal individuals. Fibrinogen Bethesda II exhibited normal migration during electrophoresis in polyacrylamide gel (in the presence of sodium dodecyl sulfate) or cellulose acetate, normal ultracentrifugal behavior, a normal chromatographic elution pattern and normal levels of hexose and sialic acid. Upon immunoelectrophoresis of whole plasma, the arc was more anodal than that produced by the fibrinogen of normal plasma. Functionally, fibrinogen Bethesda II prolonged the thrombin and Reptilase times of normal plasma and fibrinogen. The rate at which fibrinopeptides were released by thrombin or ancrod was similar to that for normal fibrinogen, and the amounts eventually reached the same levels, but a slight delay was consistently observed in the early stages of the reaction. Aggregation of fibrin monomers prepared with either thrombin or Reptilase was markedly abnormal, whereas the crosslinking (as assessed by polyacrylamide gel electrophoresis) did not differ from that of normal fibrin.