A female hemophilia A combined with hereditary coagulation factor XII deficiency: a case report

A 2-year-old Japanese girl with easy bruising and arthropathy was demonstrated to have severe hemophilia A (Factor VIII activity: less than 0.01 U/ml). She had normal 46XX karyotype. Her brother also had hemophilia A, and her mother and grandmother seem to be hemophiliac carriers. Additionally, activated partial thromboplastin time (APTT) of the patient was disproportionately prolonged and there were reduced levels of coagulation factor XII in the patients and members of the maternal trait which are compatible with heterozygous factor XII deficiency. Her father had both normal factor VIII and factor XII levels. Southern blotting analysis of genomic DNA from the propositus and family members with factor VIII and factor XII DNA probes revealed no gross alterations. This patient represents a female hemophilia A combined with heterozygous factor XII deficiency. Nonrandom inactivation of a normal X-chromosome (extreme lyonization) may be the basis for the expression of hemophilia A in this female patient.