Intracranial hemorrhage in a female leading to the diagnosis of severe hemophilia A and Turner syndrome.
BACKGROUND
Severe hemophilia A (HA) in females is a very rare phenomenon. Ignoring HA as a possible diagnose can result in fatal complications.


METHODS
We report a 3-month old girl suffering from severe hemophilia A, presenting with intracranial hemorrhage three weeks after drop down from an infant carrier. Recurrent bleeding after neurosurgery led to the diagnosis of a HA by findings of low levels of factor VIII coagulation activity (F8:C) below 1% and normal levels of factor von Willebrand activity.


METHODS
Diagnosis of hemophilia A by one stage clotting test and proof by molecular studies via long - range - PCR. Chromosome analysis in metaphases from peripheral blood lymphocytes.


RESULTS
Molecular analysis showed inversion of intron 22 as the result of a maternally inherited, distal, F8 gene inversion and chromosome analyses a 45,X karyotype indicative of Turner syndrome in our patient. Diagnosis was hampered by the female sex and the presence of neither a family history of bleeding disorders nor clinical signs of Turner syndrome.


CONCLUSIONS
Our case shows that, although uncommon in female infants, x-linked genetic bleeding disorders like HA are a possible diagnosis by very different reasons. Rare bleeding disorders, although not expected, might be present and the combined clinical, laboratory and genetic analysis are needed to establish the final diagnosis. Repetitive prolonged aPTT and clinical bleeding signs should lead to further hemostasiological investigations. An algorithm for hemostasiological investigations in case of unexplained clinical bleeding is given.
Universitätsklinikum Düsseldorf, Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Duesseldorf, Germany. weinspach@med.uniduesseldorf.de
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S
Weinspach
M
M
Siepermann
J
J
Schaper
S
S
Sarikaya-Seiwert
H
H
Rieder
M
M
Gerigk
T
T
Höhn
H-J
HJ
Laws
D007446:Chromosome Inversion / Q000235:genetics; D003937:Diagnosis, Differential; D005169:Factor VIII / Q000008:administration & dosage; D005260:Female; D016489:Head Injuries, Closed / Q000150:complications / Q000601:surgery; D006407:Hematoma, Epidural, Cranial / Q000175:diagnosis / Q000601:surgery; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D020300:Intracranial Hemorrhages / Q000175:diagnosis* / Q000601:surgery; D007438:Introns / Q000235:genetics; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D010294:Parietal Bone / Q000293:injuries; D016133:Polymerase Chain Reaction; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000601:surgery; D012086:Reoperation; D012887:Skull Fractures / Q000175:diagnosis / Q000601:surgery; D014057:Tomography, X-Ray Computed; D014424:Turner Syndrome / Q000175:diagnosis* / Q000235:genetics
C078147:F8 protein, human; D005169:Factor VIII