Hemophilia in a Chromosomal Female - An Extreme Example of Lyonization?

Severe Factor (F.) VIII deficiency is rare in females. We have previously reported two (unrelated) females with 1-3% F. VIII activity (Jour. Pediatr. 74:265-271, 1969). This report concerns a third Michigan female with Hemophilia A. Although this 12 year old girl’s F. VIII activity has ranged from 1-3% she has had only occasional hemarthroses. Her bleeding time is normal, her platelets aggregate normally with ristocetin and F. VIII antigen quantitation has varied from 1.02-1.40 μ/ml. In addition, platelet retention in a glass bead column has been normal. Her father has classical hemophilia A (F. VIII activity <1%, F. VIII antigen 1.61 μ/ml., normal bleeding time and normal platelet aggregation with ristocetin), while her mother appears to be normal (F. VIII activity 90-105% with corresponding values for F. VIII antigen, normal bleeding time and normal platelet aggregation with ristocetin). The child’s only sibling, a 9 year old sister has a F. VIII activity of 40-46%, F. VIII antigen of 1.40 μ/ml., normal bleeding time and normal platelet aggregation with ristocetin. While both girls are obligate carriers, one can only speculate on the reasons for the very low levels of F. VIII activity in the propositus. Although it is possible that there was a spontaneous mutation in the propositus’ maternal X chromosome, it seems likely that her 1-3% F. VIII activity reflects an extreme degree of lyonization.