RESUMO
Haemophilia A and B are rare X-lined 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) <0.01 U mL(-1)) or moderately severe (FVIII/FIX 0.01-0.05 U mL(-1)) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi-centre 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. Twenty-two severe/moderate haemophilia A/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health-related quality of life (HR-QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease- and treatment-related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X-chromosome inactivation pattern (XIP), were primary determinants of severity. HR-QoL 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-controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue-specific FVIII and FIX expression.
Assuntos
Hemofilia A/epidemiologia , Hemofilia B/epidemiologia , Fenótipo , Análise Citogenética , Fator IX/genética , Fator VIII/genética , Feminino , Hemofilia A/complicações , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Hemofilia B/complicações , Hemofilia B/diagnóstico , Hemofilia B/tratamento farmacológico , Humanos , Masculino , Mutação , Qualidade de Vida , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos/epidemiologiaRESUMO
Severe drug-induced thrombocytopenia (DIT) is a relatively rare, but potentially lethal, complication of pharmacological therapy. Quinine, a drug commonly used for the treatment of leg cramps, is one of the most frequent causes of DIT. This article reports a case of quinine-induced thrombocytopenia (QIT) and reviews the literature on the subject.
