An Acquired Inhibitor of Fibrin Stabilization Associated With Isoniazid Therapy: Clinical and Biochemical Observations

A patient who bled seriously while taking isoniazid was found to have an inhibitor of fibrin stabilization. The bleeding appeared to cease soon after the isoniazid was discontinued, although the plasma still contained potent inhibitor activity. This activity gradually disappeared over several weeks. The inhibitor was precipitated at 50% saturation with ammonium sulfate, migrated in the beta area on zone electrophoresis, and was found in the second peak on Sephadex G-200 gel filtration. Inhibitor activity persisted after heating to 90°C. Fibrinogen isolated from the patient’s plasma lacked factor XIII activity but did not contain measurable inhibitor activity. When the rate of incorporation of 14 C-putrescine into casein was utilized to study the kinetics of the inhibitor, it was shown that the inhibitor acted reversibly and that it competed with the amine donor, 14 C-putrescine. The mechanism whereby isoniazid led to the development of the inhibitor is unknown.