Fibrinogen Bethesda: a congenital dysfibrinogenemia with delayed fibrinopeptide release

A dysfibrinogenemia (fibrinogen Bethesda) was detected in a 9 yr old male of Mexican-English extraction who had a lifelong history of mild bleeding diathesis. The prothrombin and partial thromboplastin times were moderately prolonged; the thrombin and Reptilase times were markedly prolonged. The plasma fibrinogen level was normal by conventional methods but was markedly reduced by the Clauss method. Results of all other tests for clotting factors, fibrinolysis, antithrombin levels, clot stabilization, and fibrin(ogen) degradation products were normal. The patient's plasma and fibrinogen inhibited the clotting of normal plasma or fibrinogen by thrombin. Family studies revealed that the propositus' mother and two siblings exhibited these abnormalities to a lesser degree and indicated an autosomal dominant inheritance. Fibrinogen Bethesda was similar to normal fibrinogen in the following respects: metabolic turnover time (measured in the propositus' mother); immunodiffusion, ultracentrifugal, electrophoretic (on cellulose acetate or polyacrylamide gel), and chromatographic (on DEAE-cellulose) characteristics; sialic acid content; and aggregation of fibrin monomers. By contrast, fibrinogen Bethesda gave an abnormal immunoelectrophoretic pattern especially when whole plasma (as opposed to purified fibrinogen) was examined, and it showed a pronounced decrease in the rate of fibrinopeptide release by thrombin. This decrease, which was shown to involve both fibrinopeptides A and B, distinguishes fibrinogen Bethesda from previously reported dysfibrinogenemias.