A New Haemorrhagic Disorder with Defective Fibrin Stabilization and Cryofibrinogenaemia

Summary. An acquired haemorrhagic syndrome is described in which the failure of haemostasis is due to impaired crosslinking of fibrin. This defect, demonstrated by both monochloroacetic acid clot‐solubility test and disc‐gel electrophoretic analysis of individual fibrin chains, existed despite normal fibrin stabilizing factor (factor XIII) levels in the patient's plasma. Activation of the factor by thrombin, measured by amine incorporation into casein, was normal. The unique molecular defect in this patient could be fully accounted for by the presence of an inhibitory IgG antibody against the crosslinking sites in fibrinogen‐fibrin. No alteration could be seen in either the rate or in the extent of the reversible aggregation of fibrin. However, large amounts of cryoprecipitate were found in the patient's plasma. This phenomenon could be reproduced in vitro by incubating the chromatographically purified IgG of the patient with normal fibrinogen at 4°C. It is conceivable that the antibody in the patient could have arisen in response to the modification of normal fibrinogen by isonicotinic acid hydrazide which the patient had ingested for 8 yr.