A Naturally Occurring Inhibitor of Christmas Factor (Factor IX)

Summary

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.

• References

• 1 Biggs R, Bidwell E. A method for the study of antiha emophilic globulin inhibitors with reference to six cases.. Brit. J. Haemat. 1959; 5: 379
• 2 Biggs R, Douglas A. S. The thromboplastin generation test.. J.clin.Path. 1953; 6: 23
• 3 Biggs R, Macfarlane R. G. Human Blood Coagulation its Disorders. 2nd edn.. Blackwell Scientific Publications; Oxford: 1957
• 4 Consden R, Kohn J. Cellulose acetate as a medium for immune-diffusion methods Nature. 1959; 183: 1512
• 5 Fantl P, Sawer s R. J, Marr A. G. Investigation of a haemorrhagic disease due to beta-prothromboplastin deficiency complicated by a specific inhibitor of thromboplastin formation.. Aust. Ann. Med. 1956; 5: 163
• 6 Hicks N. D, Pitney W. R. A rapid screening test for disorders of thromboplastin generation.. Brit. J. Haemat. 1957; 3: 227
• 7 Kohn J. An immuno-electrophoretic technique.. Nature 1957; 180: 986
• 8 Lewis J. H, Ferguson J. H, Arends T. Hemorrhagic disease with circulating inhibitors of blood clotting: anti-AHF and anti-PTC in eight cases.. Blood 1956; 9: 846
• 9 Margolius Jr. A, Jackson D. P, Ratnoff O. D. Circulating anticoagulants: a study of 40 cases and a review of the literature.. Medicine 1961; 40: 145
• 10 Oakley C. L, Fulthorpe A. J. Antigenic analysis by diffusion.. J. Path. Bact. 1953; 65: 49
• 11 O’Brien J. R. Un inhibiteur de la maladie de Christmas.. Rev. Hémat. 1957; 12: 294
• 12 Pitney W. R, Dacie J. V. A simple method of studying the generation of thrombin in recalcified plasma.. J. clin. Path. 1953; 6: 9