Haemorrhagic Syndrome of Autoimmune Origin with a Specific Inhibitor against Fibrin Stabilizing Factor (Factor XIII) *

S ummary . The biochemical defect in a patient suffering from very severe bleeding episodes was shown to be related to the presence of an inhibitor which specifically interfered only with the thrombin‐catalysed conversion of the fibrin stabilizing factor zymogen (factor XIII) into fibrinoligase, but had no effect on the transamidase activity of the latter enzyme. As such, it differed from other known inhibitors of the fibrin stabilizing factor system. Inhibition could be demonstrated against both human and bovine factor XIII. In terms of neutralizing equivalents, the patient's plasma contained about a tenfold excess of the inhibitor over the factor‐XIII content found in average normal plasma. This high potency was thought to be the reason for the patient's unresponsiveness to transfusions. Precipitation with ammonium sulphate, followed by chromatographic purification on DEAE‐cellulose, allowed recovery of the inhibitor in good yield in the ‘IgG immunoglobulin’ fraction. Since, prior to the onset of bleeding episodes at about 50 yr of age the patient received no transfusions, it could be assumed that the inhibitor was of autoimmune origin. Though the cause of the disease remains unknown, the question is raised whether previous treatment with isoniazid could be involved. Accidental modification of fibrin stabilizing factor by isoniazid could have provoked a breakdown of immunological tolerance against this component in the patient's plasma. Lorand et al (1972) have recently demonstrated the modification of proteins with isoniazid in enzymatic reactions.