Fibrinogen Caracas V, an abnormal fibrinogen with an A alpha 532 Ser -> Cys substitution associated with thrombosis

A new dysfibrinogenemia associated with thrombophilia has been identified i n a Venezuelan kindred. Thrombin and Reptilase times were prolonged and the accelerating capacity of the patient's fibrin on the t-PA-induced plasmino gen activation was decreased. In addition the affinity of fibrinogen for pl asminogen was diminished. Permeability and electron microscopy studies reve aled that the abnormal clot was made up of thin and densely packed fibres g iving rise to a reduced fibrin gel porosity. This was confirmed by turbidit y studies showing a decreased fibre mass/length ratio. Affected members wer e heterozygous for an Aa 532 Ser-->Cys mutation as demonstrated by genetic analyses. This abnormal fibrinogen has been designated as Fibrinogen Caraca s V. The family study showed a convincing association between the mutation and thrombotic manifestations, The thrombotic tendency may be ascribed to l ack of accelerating capacity of fibrin to induce fibrinolysis caused by an abnormal clot structure with thin fibres and reduced porosity.