A Naturally Occurring Inhibitor of Christmas Factor (Factor IX)

Abstract

The presence of a circulating anticoagulant in the plasma of a 37-year old man with Christmas-disease resulted in failure of response to transfusion, but did not otherwise affect the clinical severity of his disease. The circulating anticoagulant inhibited blood thromboplastin formation, but was inactive in the presence of brain extract or preformed blood thromboplastin. Its physicochemical properties are described. Evidence is presented that the anticoagulant is a specific irreversible inhibitor of factor IX. Its effect on thrombin generation is compared quantitatively with its inhibitory action against factor IX. Immunological tests provided no evidence that the inhibitor was an antibody. The patient was found to respond less actively to immunisation with tetanus toxoid than his brother, whose blood contained no inhibitor. Transfusion of 520 ml of the patient’s plasma into a normal subject was followed by a transitory fall of the recipient’s serum factor IX, and a somewhat more prolonged disorder of prothrombin consumption. ^* Present address: The Hospital for Sick Children, Great Ormond Street, London, W.C. 1.