Consensus on the investigation of thrombophilia in women and clinical management.

OBJECTIVE: To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. METHODOLOGY: A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. CONCLUSION: The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

Consensus on the investigation of thrombophilia in women and clinical management / Consenso sobre a investigação de trombofilia em mulheres e manejo clínico

ABSTRACT Objective To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. Methodology A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. Conclusion The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

RESUMO Objetivo Padronizar a investigação e o manejo clínico de mulheres com anormalidades clínicas e exames laboratoriais sugestivos de trombofilia, para melhorar a abordagem antitrombótica e otimizar a indicação de exames laboratoriais. Metodologia Foi conduzida discussão incluindo 107 médicos (ginecologistas/obstetras, hematologistas e cirurgiões vasculares) participantes de um fórum realizado no Hospital Israelita Albert Einstein, em São Paulo (SP). Como critério mínimo, estabeleceu-se concordância de 80% em votação para cada recomendação de conduta registrada em documento como diretrizes finais. Os casos em que a concordância esteve abaixo de 80% foram rediscutidos, para definir consenso na conduta. Conclusão A padronização e o estabelecimento de consenso institucional, com sugestões para abordagem clínica, contribui para melhorar o manejo do grupo a ser avaliado e minimizar os riscos de intercorrências. Este foi o primeiro consenso nacional sobre investigação de trombofilia em mulheres.

Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome / Mutações no gene da cadeia leve da ferritina em duas famílias brasileiras com síndrome hereditária hiperferritinemia-catarata

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5'UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5'UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice.

RESUMO A síndrome hereditária hiperferritinemia-catarata é uma doença genética autossômica dominante associada a mutações na região 5'UTR do gene da cadeia leve da ferritina. Estas mutações elevam os níveis de ferritina, mesmo na ausência de sobrecarga de ferro. Os pacientes também desenvolvem catarata bilateral precocemente, devido ao acúmulo de ferritina no cristalino, e muitos são erroneamente diagnosticados como portadores de hemocromatose, sendo tratados de maneira inadequada. Os primeiros casos foram descritos em 1995, e diversas mutações já foram identificadas. Entretanto, essa síndrome ainda é pouco conhecida. Relatamos dois casos de famílias brasileiras, não relacionadas, com suspeita clínica da síndrome, que foram atendidas em nosso serviço. Para o diagnóstico definitivo, os pacientes afetados, seus pais e irmãos foram submetidos à pesquisa de mutação do gene ferritina, por sequenciamento de Sanger da região 5'UTR. Foram encontradas mutações do tipo polimorfismo de nucleotídeo único nos pacientes afetados, já descritas anteriormente. O teste auxiliou no diagnóstico preciso da doença e é importante ser divulgado, para ser incorporado na prática clínica.

Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome.

Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5'UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5'UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice.

Uso de gemtuzumabe ozogamicina combinado com quimioterapia convencional em pacientes com leucemia mieloide aguda / Use of gemtuzumab ozogamycin combined with conventional chemotherapy in patients with acute myeloid leukemia

Objective: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. Methods: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycincombined with conventional therapy and their outcome was analysed by reviewing their medical records. Results: Overall response rate was 58%, with 43% achieving complete response, with a median followup of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. Conclusion: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may benefit from this treatment.

Objetivo: Analisar a evolução de pacientes tratados com gemtuzumabe ozogamicina combinado à terapêutica convencional no Hospital Israelita Albert Einstein. Métodos: 14 pacientes que tinham alto risco (leucemia secundária, citogenética desfavorávele doença refratária) foram tratados com gentuzumabe ozogamicina associado à terapêutica convencional, e sua evolução foi analisada por meio de seus prontuários médicos. Resultados: A taxa total de resposta foi de 58%, com 43% chegando a resposta completa, em acompanhamento médio de 11 meses, e três meses com intervalo de sobrevivência livre. Foram a óbito 11 pacientes, 6 deles por leucemia mieloide aguda. Somente quatro pacientes apresentaram graus 3 a 4 de toxicidade e apenas um paciente teve síndrome de obstrução sinusoidal após transplante de medula. Conclusão: Gemtuzumabe ozogamicina associado à terapêutica quimioterápica convencional éum tratamento factível em pacientes com leucemia mieloide aguda. Contudo, novos estudos são necessários para esclarecer qual o subgrupo de pacientes que pode se beneficiar desse tratamento.

Use of gemtuzumab ozogamycin combined with conventional chemotherapy in patients with acute myeloid leukemia.

OBJECTIVE: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. METHODS: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycin combined with conventional therapy and their outcome was analysed by reviewing their medical records. RESULTS: Overall response rate was 58%, with 43% achieving complete response, with a median follow-up of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. CONCLUSION: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may beneft from this treatment.