Recurrent Venous Thrombosis Related To A Hereditary Dysfibrinogen With Abnormal Crossed Immunoelectrophoretic Pattern

Abstract

A 24 year old man with a history of multiple recurrent venous thrombosis was found to have a qualitatively abnormal fibrinogen. Plasma fibrinogen concentration by a kinetic thrombin time method was 135mg% as compared to 150mg% by the gravimetric method of Ratnoff and Menzie. The thrombin, reptilase and Russell viper venom times were all approximately 50% longer than the normal values. Neither the thrombin time nor reptilase time was corrected upon addition of CaCl2. Antigenic quantitation by Laurell immunoelectrophoresis gave a value of 320mg%. On Ouchterlony immunodiffusion plate, the patient’s plasma and normal plasma showed a line of identity. The patient’s fibrinogen had a normal rate of migration by one-dimensional immunoelectrophoresis but it exhibited an abnormal pattern upon crossed immunoelectrophoresis. The abnormality is characterized by the presence of a shoulder on the anodal side of the fibrinogen peak. Family studies revealed that the fibrinogen defect was inherited as an autosomal dominant trait. To determine whether recurrent venous thrombosis is related to increased viscosity due to the abnormal fibrinogen, fibrinogen was purified by the method of BlombSck and the relative viscosity of fibrinogen solution was determined. Preliminary data were suggestive of an increased viscosity of the patient’s fibrinogen. These findings indicate that the immunologically abnormal dysfibrinogen may be responsible for recurrent venous thrombosis because of alteration of the physicochemical properties of the fibrinogen molecule.