Familial antithrombin III deficiency as pathogenesis of deep venous thrombosis

A family including 18 members with decreased antithrombin III (AT III), measured with both a biological and an immunochemical method, is described. The pattern found on crossed immunoelectrophoresis, using heparin in the agarose in the first run, was normal, though the peaks were low. This suggests decreased synthesis of a normal protein in the affected members. AT III deficiency occurred in both the paternal and the maternal branch, of the above 18 persons had had at least one thromboembolic episode. Some of the episodes had been precipitated by the presence or occurrence of some predisposing event or circumstance. This suggests the possible occurrence of a gene making some of the maternal family members more susceptible to certain trigger factors, such as surgery, infection, pregnancy, and the puerperium. The mode of inheritance filled all the criteria for autosomal dominant transmission. Prophylactic treatment, preferably oral anticoagulants and/or dextran, is recommended for all persons with a low AT III concentration in any situation known to increase the predisposition to thrombosis. The effect of heparin in these patients is impaired since the heparin co-factor, which is identical with AT III, is lowered.