RESUMO
Approximately 2% of the general population have an underlying inherited bleeding disorder, which, for adolescents and young adult women, has both physical risks and adverse psychosocial effects. Heavy menstrual bleeding can be the first sign of an underlying bleeding disorder such as von Willebrand disease and the X-linked bleeding disorders hemophilia A and B. Connective tissue disorders such as Ehlers-Danlos syndrome, in particular the hypermobile subtype, are relatively frequent in the general population and can also cause bleeding symptoms from impaired hemostasis due to defective collagen. For more than 20 years, the American College of Obstetricians and Gynecologists (ACOG) has recommended screening adolescents and young adult women for bleeding disorders when they present with heavy menstrual bleeding. Despite this directive, there is a significant gap from symptom onset to time of diagnosis in this patient population. We must work to effectively close this diagnostic gap by consistently obtaining thorough bleeding histories, performing the appropriate laboratory evaluations, working collaboratively with hematologists, and using tools and materials promoted by ACOG. Improved screening and earlier diagnosis of these individuals can have far-reaching effects that are not limited to heavy menstrual bleeding management and extend to peripartum considerations and prenatal counseling.
Assuntos
Menorragia , Doenças de von Willebrand , Gravidez , Humanos , Feminino , Adolescente , Adulto Jovem , Menorragia/diagnóstico , Menorragia/etiologia , Hemorragia/etiologia , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/complicações , Bases de Dados Genéticas , LaboratóriosRESUMO
PURPOSE OF REVIEW: To summarize the recent literature related to female hemophilia A carriers with respect to prevalence in the population, the impact of baseline factor VIII levels and other influences on bleeding phenotype, and clinical management needs. RECENT FINDINGS: Many female hemophilia A carriers are at risk for abnormal bleeding, yet they are underrecognized by healthcare providers and their bleeding symptoms are underreported. Low FVIII levels are consistently associated with clinically significant bleeding and correlate well with skewed X chromosome inactivation (XCI). Most interestingly, bleeding tendency is also observed in some hemophilia A carriers with normal factor VIII levels and requires further investigation. Well controlled studies investigating peripartum and periprocedural FVIII levels and adequate hemostatic treatment are necessary to inform management guidelines. SUMMARY: Prevalence and bleeding tendency of hemophilia A carriers remain underreported, despite a significant proportion having low FVIII levels. Skewed XCI may explain low FVIII but does not explain the bleeding risk encountered in a larger proportion of hemophilia A carriers with random XCI and borderline/normal FVIII.
Assuntos
Cromossomos Humanos X/genética , Fator VIII , Hemofilia A , Hemorragia , Heterozigoto , Fenótipo , Fator VIII/genética , Fator VIII/metabolismo , Feminino , Hemofilia A/sangue , Hemofilia A/genética , Hemorragia/sangue , Hemorragia/genética , HumanosAssuntos
Sequenciamento do Exoma , Hemofilia A , Fator VIII/genética , Hemofilia A/genética , Humanos , FenótipoRESUMO
BACKGROUND: Sorafenib promotes apoptosis through downstream pathways that can be deregulated in CRPC. We hypothesized that sorafenib could overcome chemotherapy resistance in CRPC. PATIENTS AND METHODS: Eligible patients were those whose disease had progressed during chemotherapy (docetaxel or mitoxantrone) or within 12 weeks of stopping either. Patients then continued or resumed their last chemotherapy regimen with the addition of sorafenib 400 mg twice daily. Patients received a maximum of 6 cycles of chemotherapy/sorafenib followed by sorafenib alone until disease progression. The primary end point was combination safety. Secondary end points were overall response, percentage of SD, and time to progression (TTP). RESULTS: Twenty-two patients (21 evaluable) were enrolled (16 patients with Gleason score ≥ 7). Median age was 68 years (range, 59-83 years). Median prostate-specific antigen (PSA) was 142 ng/dL (range, 13.6-9584). Visceral and bone disease were present combined in 9 patients (41%). Ten patients (47.6%) showed biochemical response (19% with > 50% PSA decline) and 16 patients (76%) achieved radiographic stability (according to Response Evaluation Criteria for Solid Tumors) after starting sorafenib for a median duration of 6 months (range, 4-12 months). Grade 3/4 nonhematologic toxicities were fatigue (n = 7, 32%), palmar-plantar erythrodysesthesia (n = 4, 18%). Dose reduction of sorafenib occurred at least once in 15 patients (68%) because of palmar-plantar erythrodysesthesia (22%) and fatigue (22%). With a median follow-up of 19 months (range, 3-46 months), median overall survival was 8 months. TTP according to PSA level was 3 months and TTP according to imaging studies and/or clinically was 6 months. Median number of treatment cycles given was 6 (range, 1-10). CONCLUSION: Sorafenib can be combined safely with chemotherapy and in some patients overcomes chemotherapy resistance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/mortalidade , Sorafenibe , Análise de Sobrevida , Taxoides/administração & dosagem , Falha de TratamentoRESUMO
Diffuse large B-cell non-Hodgkin lymphoma (DLBCL) is a disease of the elderly, but our current guidelines and treatment paradigms for this disease are based on studies that have mainly enrolled younger patients. Because the number of people living beyond the age of 80 increased by more than 250% between 1960 and 2000, and since it is expected that the population over the age of 75 will triple by 2030, understanding how these elderly patients should be treated is paramount to improving outcomes for this potentially curable lymphoma. In this review, we outline the scope of the problem; we define "the elderly" and identify challenges in assessing this patient population. We also summarize pivotal studies that have been conducted in these elderly patients and suggest an algorithm to aid clinicians in making treatment decisions when faced with DLBCL patients older than 80.