Use of Porcine Factor VIII in the Management of Seventeen Patients with Factor VIII Antibodies

Summary

A polyelectrolyte-fractionated porcine factor VIII concentrate was given to 16 hemophiliacs with anti-F VIII antibodies (Ab) and to a woman with post-partum-acquired Ab during 24 courses of treatment including three major surgical procedures. Before treatment, antiporcine F VIII Ab was always lower than antihuman F VIII Ab, with a median cross reactivity of 32%. After treatment, the mean rise in F VIII was 1.5 U/dl/Unit infused/Kg b.w. and in vivo recovery was 50% of the theoretical values. Anamnestic rises in anti-porcine F VIII Ab (3 × the baseline titer) were seen after 9 of 22 courses of treatment with porcine F VIII only; similar rises in anti-human F VIII Ab, after 6 courses of treatment; median cross reactivity did not change significantly. Lower than expected increases in plasma F VIII without marked changes in Ab titers and severe thrombocytopenia occurred during surgery in two patients. Porcine F VIII is a rational and effective therapeutic choice for patients who have anti-human Ab titers above 10 U/ml; it can solve clinical situations that would otherwise be very difficult to manage; anamnesis is perhaps less frequent than after human F VIII; however, the incidence of thrombocytopenia, resistance and other side- effects is still higher than desirable.

Keywords

Factor VIII - Polyelectrolyte - Factor VIII antibodies - Hemophilia therapy

• References

• 1 White II GC, McMillan CW, Blatt PM, Roberts HR. Factor VIII inhibitors: a clinical overview. Am J Haematol 1982; 13: 335-342
• 2 Lusher JM, Shapiro SS, Palascak JE, Rao AV, Levine PH, Blatt PM. The Hemophilia Study Group. Efficacy of prothrombin- complex concentrates in hemophiliacs with antibodies to factor VIII N Engl J Med 1980; 303: 421-425
• 3 Sjamsoedin LJ M, Heijnen L, Mauser-Bunschoten EP, van Geijls-wilk JL, van Houwelingen H, van Asten P, Sixma JJ. The effect of activated prothrombin-complex concentrate (Feiba) on joint and muscle bleeding in patients with hemophilia A and antibodies to factor VIII. N Engl J Med 1981; 305: 717-721
• 4 Macfarlane RG, Mallam PC, Witts LJ, Bidwell E, Biggs R, Fraenkel GJ, Honey GE, Taylor KB. Surgery in hemophilia. The use of animal antihemophilic globulin and human plasma in thirteen cases Lancet 1957; 2: 251-259
• 5 Biggs R. Major surgery in hemophilic patients. In: Treatment of Haemophilia and other Coagulation Disorders. Biggs R, Macfarlane RG. (eds) pp 166-194 Blackwell Scientific Publications; Oxford: 1966
• 6 Johnson AJ, Macdonald VE, Semar M, Fields JE, Schuck L, Lewis C, Brind J. Preparation of the major plasma fractions by solid-phase polyelectrolytes. J Lab Clin Med 1978; 92: 194-210
• 7 Middleton S. Polyelectrolytes and preparation of factor VIIIC. In: Unresolved Problems in Haemophilia. Forbes CD, Lowe GD O. (eds) pp 109-120 MIP Press; Lancaster: 1982
• 8 Shulman NR, Hirschman RJ. Acquired Hemophilia. Trans Assoc Am Physicians 1969; 82: 388
• 9 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
• 10 Bidwell E. Immunological aspects of haemophilia. In: Treatment of Haemophilia and other Coagulation Disorders. Macfarlane RG. (eds) pp 93-106 Blackwell Scientific Publications; Oxford: 1966
• 11 Hardisty RM, Macpherson JC. A one-stage factor VIII (anti- haemophilic globulin) assay and its use on venous and capillary plasma. Thrombos Diathes Haemorrh 1962; 7: 215-221
• 12 Kasper CK, Aledort LM, Counts RB, Edson JR, Fratantoni JC, Green D, Hampton JR, Hilgartner MW, Lazerson J, Levine PH, MacMillan CW, Pool JG, Shapiro SS, Shulman NR, Van Eys JA. A more uniform measurement of factor VIII inhibitors. Thrombos Diathes Haemorrh 1975; 34: 869-872
• 13 Ruggeri ZM, Gagnatelli G, Capitanio A, Martello L, Mannucci PM. Clinical study of the inhibitors of factor VIII. Thrombos Diathes Haemorrh 1971; Suppl (Suppl. 43) 367-371
• 14 Allain JP, Roberts HR. Treatment of acute bleeding episodes in hemophilic patients with specific Factor VIII antibodies. In: Handbook of Hemophilia. Brinkhous KM, Hemker HC. (eds) pp 659-671 Excerpta Medica; Amsterdam: 1975
• 15 Biggs R. Plasma concentrations of factor VIII and factor IX and treatment of patients who do not have antibodies directed against these factors. In: The Treatment of Haemophilia A and B and von Willebrand’s Disease. Biggs R. (ed) pp 110-126 Blackwell Scientific Publications; Oxford: 1978
• 16 Hewitt P, Mackie IJ, Machin SJ. Highly purified factor VIII in hemophilia A. Lancet 1982; 1: 741-742
• 17 Verroust F, Allain JP. Immune response induced by porcine factor VIII in severe hemophiliacs with antibody to F VIII. Thromb Haemostas 1982; 48: 238
• 18 Exner T, Rickard KA. Anamnestic response to high purity porcine AHF. Thromb Haemostas 1983; 50: 623
• 19 Colvin BT, Ainsworth M, Buckley C. Experience with highly purified porcine factor VIII in a patient with hemophilia A and a factor VIII inhibitor. Clin Lab Haematol 1983; 5: 55-59
• 20 Erskine JG, Davidson JF. Anaphylactic reaction to low-molecular-weight porcine factor VIII concentrates. Br Med J 1981; 282: 2011-2012
• 21 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