Disappearance of Antibodies to Factor VIII in a Patient with Acquired Haemophilia and Carcinoma of the Pancreas During Cytotoxic Therapy with Fluorouracil and CCNU

Summary

An inhibitor to clotting factor VIII (anti-VIII: C) developed in a 70 year old woman with carcinoma of the pancreas three months after palliative by-pass surgery. A life-threatening sublingual haemorrhage was controlled by infusion of human factor VIII concentrate in high dosage. With the objective of reducing pancreatic tumour size, combination cytotoxic therapy with fluorouracil and CCNU was given. Reduction in the size of the tumour was associated with disappearance of anti-VIII:C, reappearance of normal quantities of clotting factor VIII (VIII: C) in the plasma and resolution of the bleeding tendency. The anti-VIII: C was characterised as being predominantly of the IgG₄ sub-class with k light chains. In vitro and in vivo studies showed the inactivation of VIII: C by anti-VIII: C was markedly non-linear. Normal quantities of factor VIII coagulant antigen (VIII: CAg) were detected in the patient’s plasma when VIII: C levels were negligible.

Keywords

Acquired haemophilia - Factor VIII antibodies - Carcinoma of pancreas - CCNU - Fluorouracil

• References

• 1 Editorial. Acquired haemophilia. Lancet 1981; 1: 255
• 2 Al-Ismail SA D, Parry DH, Moisey CU, Bloom AL. Factor VIII inhibitor and bronchogenic carcinoma. Thromb Haemostas 1979; 41: 291-295
• 3 Nilsson IM, Lamme S. On acquired hemophilia A. Acta Med Scand 1980; 208: 5-12
• 4 Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to factor VIII. Thromb Haemostas 1981; 45: 200-203
• 5 Allain JP, Gaillandre A, Frommel D. Acquired haemophilia: functional study of antibodies to factor VIII. Thromb Haemostas 1981; 45: 285-289
• 6 Kasper CK, Aledort LM, Counts RB, Edson JR, Fratantoni J, Green D, Hampton JW, Hilgartner MW, Lazerson J, Levine PH, McMillan CW, Pool JG, Shapiro SS, Shulman NR, van Eys J. A more uniform measurement of factor VIII inhibitors. Thrombos Diathes Haemorrh 1979; 34: 869-872
• 7 Rotblat F, Tuddenham EG D. Assays based on a haemophilic and an acquired antibody to VIII :C. Thromb Res 1981; 21: 431-445
• 8 Heide K, Schwick HG. Salt fractionation of immunoglobulins. Handbook of Experimental Immunology. Weir DM. (ed) Blackwell Scientific Publications; Oxford: 1978. p 75
• 9 Feinstein DI, Rapaport SI, McGehee WG, Patch MJ. Factor V anticoagulants: clinical, biochemical and immunological observations. J Clin Invest 1970; 49: 1578-1588
• 10 Kernoff PB A, Thomas ND, Lilley PA, Matthews KB, Goldman E, Tuddenham EG D. Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII. Blood 1984; 63: 31-41
• 11 Biggs R. Plasma concentrations of factor VIII and factor IX and treatment of patients who do not have antibodies directed against these factors. The Treatment of Haemophilia A and B and von Willebrand’s Disease. Biggs R. (ed) Blackwell Scientific Publications; Oxford: 1978. p l23
• 12 Shulman NR, Hirschman RJ. Acquired hemophilia. Trans Assoc Am Physicians 1969; 82: 388-397
• 13 Kernoff PB A. The relevance of factor VIII inactivation characteristics in the treatment of patients with antibodies directed against factor VIII. Br J Haematol 1972; 22: 735-742
• 14 Gawryl MS, Hoyer LW. Inactivation of factor VIII coagulant activity by two different types of human antibodies. Blood 1982; 60: 1103-1109
• 15 Hultin MB, London FS, Shapiro SS, Yount WJ. Heterogeneity of factor VIII antibodies: further immunochemical and biologic studies. Blood 1977; 49: 807-817
• 16 Allain JP, Gaillandre A, Lee H. Immunochemical characterization of antibodies to factor VIII in hemophilic and nonhemophilic patients. J Lab Clin Med 1981; 97: 791-800