Репозиторий Университета

© 2018, Pleiades Publishing, Inc. Hemophilia A is a recessive X-linked hereditary disease, so its manifestation in women is extremely rare and can be a result of an asymmetric X-chromosome inactivation or, even more rarely, of a presence of mutations in both FVIII gene alleles. We conducted a mutation screening of the FVIII gene in two female patients with clinical hemophilia A manifestation in this study. One patient had a hereditary disease; the second one was diagnosed with acquired hemophilia A as an adult. Both patients carried the same missense mutation His2026Arg. The patient with the hereditary form of the disease also had previously known microinsertion c.4379_4380 insA (p.Asn1460Lys-fs*1). We found no additional aberrations by sequencing of all functionally significant parts of the factor VIII gene of the patient with acquired hemophilia but showed clear asymmetric inactivation of X-chromosomes. Therefore, one of the possible explanations for the emergence of the hemophilic syndrome in this case can be the delayed manifestation of the FVIII gene germline mutation owing to the enhancement of hematopoiesis clonality with age.

© 2018 Media Sphera Publishing Group. All rights reserved. The article provides review of possible mechanisms of inhibitor coagulopathies, in particular of acquired hemophilia A. This pathology is an extremely rare disease occurring in 1-2 cases in 1 million per year. In the present study we provide data for two clinical cases of hemophilia A in women. These cases had different development mechanisms, although both women have a newly discovered missense mutation His2026Arg in the VIII factor gene. The matter of main interest is the description of the disease development in the patient with an acquired idiopathic hemophilia A with a possible disease occurrence due to an asymmetric X-chromosome inactivation (lyonization). In this particular case lyonization led to the late manifestation of the hemophilia A carrier's state and development of severe form of the inhibitor-associated acquired hemophilia A. We also discuss therapeutic approaches to these forms of the disease, considering there are no concise protocols for case management due to an extreme rarity of the pathology. Acquainting the clinical personnel working it the different areas of medicine with suchlike inhibitor coagulopathies has a major practical importance.