ACQUIRED FACTOR-VIII-C INHIBITOR ANTIBODI ES IN NONHEMOPHILIC PATIENTS

Antibodies against factor VIII:C occur in about 5-15% of hemophilia A patients and induce refractoriness to factor VIII:C infusions. These a ntibodies are mostly of IgG class. In very rare cases factor VIII:C in hibitors also develop in nonhemophilic patients. Although there are an ecdotal reports that these antibodies may disappear spontaneously, in the majority of patients the clinical course is characterized by sever e hemorrhages. During the last ten years we treated 9 nonhemophilic pa tients with acquired factor VIII:C inhibitors at our clinic. In most c ases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII:C level. Therapy with F VIII:C concentrates did not produce the expected increase. Measurement of F VIII:C inhibitor levels (Bethesda Units = BU) revealed values in the range between 2 and 108 BU. Immuno suppressive therapy in patients with >5 BU using azathioprine or cyclo phosphamide in combination with prednisone lead to complete disappeara nce of the inhibitor, normalization of the coagulation tests, and comp lete remission of the bleeding tendency in 7 patients within 6 weeks. During pregnancy only prednisone should be given. On the other hand in women with post-partum factor VIII inhibitors, steroid treatment appe ars to be not superior to no treatment, but immunosuppression with cyc lophosphamide or azathioprine seems to be more effective. In emergency situations, therapy with high doses of human F VIII:C concentrate is recommended. When bleeding does not cease, the additional use of activ ated prothrombin concentrates or porcine factor VIII concentrate is in dicated. Side effects may include hepatitis and short-lived intravascu lar thrombin production.