Severe hemophilia A in a female associated with skewed X inactivation.

BONDUEL M; SCIUCCATI G; HEPNER M; RADIC P; ROSSETTI L; DE BRASI C

Buenos Aires, Argentina

Congreso; XXIX International Congress of the World Federation of Hemophilia; 2010

World Federation of Hemophilia

Female hemophilia A (HA) is a rare disorder similar to other X-linked recessive diseases. Different genetic mechanisms causing this defect were identified. We describe a 1 year-old girl who was referred in November 2009 because of a large intramuscular hematoma in the left buttock and a hematoma in one of her hands following a venous puncture. She has had hematomas since the first months of life. The coagulation assays showed an activated partial thromboplastin time (APTT) of 113 sec and factor VIII coagulant activity (FVIII:C) of 1IU/dL. She had good clinical and laboratory response to coagulation factor replacement therapy. No FVIII inhibitors, phenotypic pattern of VWD or other coagulation defects were found. She has a normal karyotype (46,XX). She also presented a spontaneous hemarthrosis of the left ankle so, prophylactic therapy with FVIII concentrate will be started. A maternal aunt and a maternal great uncle have bleeding symptoms. The coagulation assays of the mother showed an APTT of 42 sec and FVIII:C of 58 IU/dL. X-chromosome inactivation analysis by the HUMARA assay resulted in extremely skewed patterns (>95%) from both, the patient’s and her mother’s peripheral blood DNA samples. F8 gene characterization is currently under investigation. We report a female HA, who has a very rare phenotypic expression of the disease. Although patient’s carrier condition has not been confirmed by F8 molecular analysis so far, the presence of a skewed pattern of X-inactivation suggests its causative involvement in the development of severe HA symptoms in this patient.