ACQUIRED FACTOR-VIII INHIBITORS IN NONHEMOPHILIC PATIENTS

Antibodies against factor VIII occur in about 15-35% of hemophilia A p atients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although ther e are anecdotal reports that these antibodies may disappear spontaneou sly without occurrence of bleeding tendencies, in the majority of pati ents the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired fac tor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other defi ciencies of blood-clotting factors and acquired or hereditary von Will ebrand's disease were excluded. Therapy with F Hemophilia VIII concent rates did not produce the expected increase. Measurement of F VIII inh ibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in Introduction the range of 2-128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination Antibodies with methyl prednisolone led to complete disappearance of the inhibitor, normaliza tion of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinic al course is not predictable and inhibitors may disappear spontaneousl y, combined therapy with methylprednisolone and azathioprine or cyclop hosphamide is recommended for patients with bleeding tendency. In preg nancy, therapy should be started only with methylprednisolone; post-pa rtum, azathioprine should be used additionally if methylprednisolone a s a single drug does not lead to complete remission. In emergency situ ations, therapy with high doses of human factor VIII concentrate may b e used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascu lar thrombin production.