{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:53:50Z","timestamp":1790409230000,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T00:00:00Z","timestamp":1392681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Haemophilia A and B are rare X\u2010lined hemorrhagic disorders that typically affect men. Women are usually asymptomatic carriers, but may be symptomatic and, rarely, also express severe (factor VIII (FVIII) or factor IX (FIX) &lt;0.01\u00a0U\u00a0mL<jats:sup>\u22121<\/jats:sup>) or moderately severe (FVIII\/FIX 0.01\u20130.05 U\u00a0mL<jats:sup>\u22121<\/jats:sup>) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi\u2010centre retrospective study was conducted to collect a comprehensive data set on affected US girls and women, and to compare clinical observations to previously published information on haemophilic males of comparable severity and mildly affected haemophilic females<jats:bold>.<\/jats:bold> Twenty\u2010two severe\/moderate haemophilia A\/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health\u2010related quality of life (HR\u2010QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease\u2010 and treatment\u2010related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X\u2010chromosome inactivation pattern (XIP), were primary determinants of severity. HR\u2010QoL was diminished by arthropathy and viral infection. Using systematic case verification of participants in a national surveillance registry, this study elucidated the genetics, clinical phenotype and quality of life issues in female patients with severe\/moderate haemophilia. An ongoing international case\u2010controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue\u2010specific FVIII and FIX expression.<\/jats:p>","DOI":"10.1111\/hae.12364","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T12:29:26Z","timestamp":1392726566000},"source":"Crossref","is-referenced-by-count":86,"title":["Severe and moderate haemophilia A and B in US females"],"prefix":"10.1111","volume":"20","author":[{"given":"D. M.","family":"Di Michele","sequence":"first","affiliation":[{"name":"Department of Pediatrics Weill Cornell Medical College New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gibb","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Weill Cornell Medical College New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Department of Social Work New York Presbyterian Hospital\u2010Weill Cornell Medical Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Public Health Weill Cornell Medical College New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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