Criteria for the differentiation of dysfibrinogenemic states.

A large number of families have now been described in whom affected individuals have within their plasmas an abnormal species of fibrinogen (factor I). These defects, presumably examples of the phenomenon of allotypy--i.e., the synthesis of variant forms of a normal protein--have been inherited as autosomal dominant characteristics. In the great majority of cases, clotting is abnormally slow when thrombin is added to the abnormal plasma. Sometimes this defect appears to reside in impaired release of fibrinopeptides by thrombin. In other cases, fibrinopeptide release proceeds normally, but aggregation of fibrin monomers is impeded. In the latter instance, aggregation may be abnormally slow or, once it begins, it may proceed at a normal rate. Curiously, a bleeding tendency is more likely to occur in patients in whom fibrinopeptide release is impaired, while dehiscence of operative wounds rarely complicates dysfibrinogenemias associated with impaired aggregation of fibrin monomers; thrombosis has been described in both groups of patients. Most of the reported cases may be distinguished by functional criteria and by the physicochemical behavior and biochemical nature of the abnormal protein. Additonally, one family has been described in which plasma clots abnormally rapidly upon addition of thrombin, and two others in which crosslinking of fibrin by fibrin-stabilizing factor (factor XIII) is defective.