We have investigated 31 Bulgarian patients suffering from severe hemophilia A and B below 1%, as determined by factor VIII and factor IX activity levels, respectively. Three hemophilia A patients (10%) had surprisingly mild presentation, manifested by fewer bleeding episodes. One of these patients had a maternal cousin suffering from a full-blown severe form of hemophilia A. One patient, with a milder clinical course, had never needed either plasma or factor VIII infusions, even though his factor VIII level was below 1%. Two hemophilia A patients with low levels of factor VIII but a mild clinical course, shared a common molecular defect in the factor VIII gene, a large inversion disrupting the gene, resulting in virtually nonexistent factor VIII activity.

No thrombotic episodes have been reported among these three patients thus far, although one patient was 60 years of age at the time of investigation. The milder clinical phenotype was not found to be associated with lack of arthropathy because the milder bleeding tendency was manifested exclusively by a decrease in the number of bleeding incidents. Arthropathy was apparent in older patients.

Heterozygous factor V Leiden mutation (G1691A) was found in one pediatric patient who did not display amelioration in the clinical phenotype. His bleeding disorder became obvious in early infancy. Up to the present time, he has had several bleeding episodes and frequently needs treatment with factor VIII preparations. No thrombotic episodes have been reported so far.