A Family with an Unusual form of Factor VIII Deficiency

The propositus presented with post-traumatic and post-surgical bleeding suggestive of mild hemophilia. The factor VIII level was 21%; the bleeding time and platelet function assays were normal. Although 6 other male family members had similar bleeding histories, coagulation workups had not been performed on these or other relatives. Forty-three members were therefore studied in detail with the following findings: (1) factor VIII levels varied from 7.5-85% (mean - 36%) among affected males. (2) normal factor VIII-related antigens, factor IX and XI levels, and prothrombin complex activities. (3) much better correlation between bleeding histories and degree of prolongation of activated partial thromboplastin times than factor VIII activities. (4) inheritance that appears to be X-linked except that 6/6 grandsons of a carrier woman were affected, whereas 0/4 daughters of affected men had decreased factor VIII activity. These results are only partially consistent with a diagnosis of classical hemophilia A and suggest a variant form of hereditary factor VIII deficiency.