Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal hemoglobinuria is a chronic, multi-systemic, progressive and lifethreatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure. Paroxysmal nocturnal hemoglobinuria results from the expansion of a clone of hematopoietic cells that due to an inactivating mutation of the X-linked gene PIG-A are deficient in glycosylphosphatidylinositol-linked proteins. Early diagnosis, using flow cytometry performed on peripheral blood, the gold standard test to confirm the diagnosis of paroxysmal nocturnal hemoglobinuria, is essential for improved patient management and prognosis. The traditional therapy for paroxysmal nocturnal hemoglobinuria includes blood transfusion, anti-thrombosis prophylaxis or allogeneic bone marrow transplantation. The treatment that has recently become available is the complement blockade by the anti-C5 monoclonal antibody eculizumab. In this consensus, we are aiming to review the diagnosis and treatment of the paroxysmal nocturnal hemoglobinuria patients, as well as the early recognition of its systemic complications. These procedures express the opinions of experts and have been based on the best available evidence and international guidelines, with the purpose of increasing benefits and reducing harm to patients.

Risk factors for deferral due to low hematocrit and iron depletion among prospective blood donors in a Brazilian center

OBJECTIVE: Deferral of blood donors due to low hematocrit and iron depletion is commonly reported in blood banks worldwide. This study evaluated the risk factors for low hematocrit and iron depletion among prospective blood donors in a large Brazilian blood center.METHOD: A case-control study of 400 deferred donors due to low hematocrit and 456 eligible whole blood donors was conducted between 2009 and 2011. Participants were interviewed about selected risk factors for anemia, and additional laboratory tests, including serum ferritin, were performed. Bivariate and multivariate analyses were performed to assess the association between predictors and deferral due to low hematocrit in the studied population and iron depletion in women.RESULTS: Donors taking aspirins or iron supplementation, those who reported stomachache, black tarry stools or hematochezia, and women having more than one menstrual period/month were more likely to be deferred. Risk factors for iron depletion were repeat donation and being deferred at the hematocrit screening. Smoking and lack of menstruation were protective against iron depletion.CONCLUSION: This study found some unusual risk factors related to gastrointestinal losses that were associated with deferral of donors due to low hematocrit. Knowledge of the risk factors can help blood banks design algorithms to improve donor notification and referral.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease

BACKGROUND: Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. OBJECTIVE: To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. METHODS: The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. RESULTS: Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. CONCLUSION: The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.

Resultados maternos e perinatais em gestações complicadas por doenças falciformes / Maternal and perinatal outcomes in pregnancies complicated by sickle cell diseases

OBJETIVO: avaliar os resultados maternos e perinatais de gestações complicadas por doenças falciformes, comparando-as com portadoras de traço falciforme. MÉTODOS: este estudo é uma coorte retrospectiva, abrangendo o período de Março de 2001 a Abril de 2008, tendo sido incluídas todas as gestantes portadoras de doença falciforme (n=42) acompanhadas em hospital universitário da região sudeste do Brasil. Os resultados maternos e perinatais foram comparados com os de gestantes portadoras de traço falciforme (n=56) acompanhadas no mesmo serviço. RESULTADOS:a hemoglobinopatia SS foi diagnosticada em 42 gestantes (82,4 por cento) e a SC em nove (17,6 por cento). A idade materna foi significativamente menor no grupo com doença falciforme (média=26,0; SD=4,3) quando comparadas às com traço falciforme (média=28,7, DP=7,1; p=0,018). As seguintes complicações maternas foram significativamente mais frequentes no grupo com doença falciforme em comparação ao grupo com traço falciforme: infecção do trato urinário (25,5 versus 8,9 por cento; p=0,04), pneumonia (23,5 versus 1,8 por cento; p=0,002), hipertensão pulmonar (15,7 versus 0 por cento; p=0,002), e transfusão no parto/pós-parto (33,3 versus 5,4 por cento; p=0,001). Resultados perinatais adversos foram significativamente mais frequentes no grupo com doença falciforme quando comparados ao grupo com traço falciforme: prematuridade (49 versus 25 por cento; p=0,01), média da idade gestacional no parto (35,2 versus 37,9 semanas; p<0,001), diagnóstico de sofrimento fetal (56,9 versus 28,6 por cento; p=0,006), peso do recém-nascido <2.500g (62,7 versus 17,9 por cento; p<0,001), média do peso do recém-nascido (2.183 versus 2.923 g; p<0,001) e recém-nascidos pequenos para a idade gestacional (29,4 versus 10,7 por cento; p=0,02). Duas mortes maternas (3,9 por cento) ocorreram no grupo com doença falciforme. CONCLUSÕES: gestantes portadoras de doença falciforme apresentam maior risco para morbidade materna e resultados perinatais adversos quando comparadas às portadoras de traço falciforme.

PURPOSE: the aim of this study was to describe perinatal and maternal outcomes of pregnancies complicated by sickle cell disease (SCD), comparing to pregnancies of women with sickle cell trait (SCT). METHODS: this was a retrospective cohort study, covering the period from March 2001 to April 2008, which included all pregnant women with SCD (n=42) followed up at a university hospital in the Southeast region of Brazil. The maternal and perinatal outcomes were compared to those of pregnant women with SCT (n=56) who were followed up at the same service. RESULTS:SCD-SS was diagnosed in 42 (82.4 percent) pregnant women and SC in 9 (17.6 percent). Mean (±SD) maternal age was significantly lower in the SCD group (26.0 years) compared to SCT women (28.7±7.1 years; p=0.018). The following maternal complications were more common among women with SCD in comparison to SCT: urinary tract infection (25.5 versus 8.9 percent; p=0.04), pneumonia (23.5 versus 1.8 percent; p=0.002), pulmonary hypertension (15.7 versus 0 percent; p=0.002), and blood transfusion during delivery or postpartum (33.3 versus 5.4 percent; p=0.001). Adverse perinatal outcome was more frequent in the SCD group compared to the SCT group: prematurity (49 versus 25 percent, p=0.01); mean gestational age at delivery (35.2 versus 37.9 weeks, p<0.001); fetal distress (56.9 versus 28.6 percent, p=0.006); birth weight <2,500 g (62.7 versus 17.9 percent, p<0.001); mean birth weight (2,183 versus 2,923 g, p<0.001), and small for gestational age infants (29.4 versus 10.7 percent, p=0.029). Two maternal deaths (3.9 percent) occurred in the group with SCD. CONCLUSION: Pregnant women with SCD are at greater risk for maternal morbidity and for adverse perinatal outcomes than women with SCT.

Porfirias: quadro clínico, diagnóstico e tratamento / Porphyrias: clinical presentation, diagnosis and treatment

As porfirias são doenças incomuns e de herança genética na maior parte doscasos. As porfirias são divididas em eritropoiéticas, hepáticas agudas e hepáticas crônicas. Os subtipos de maior relevância clínica são a porfiria cutânea tarda e a porfiria intermitenteaguda. O diagnóstico das porfirias pode ser bastante difícil, dada a sobreposição de quadros clínicos e achados bioquímicos. A precisão do diagnóstico depende da dosagem de porfirinasurinárias e fecais, da análise da atividade enzimática de eritrócitos e, eventualmente, da pesquisa de mutações. O objetivo do presente artigo é realizar revisão literária das porfirias,com ênfase no diagnóstico e tratamento de seus diversos subtipos...

Porphyrias are uncommon diseases that have genetic inheritance in the majorityof the cases. Porphyrias are divided in: erythropoietic porphyria, acute hepatic porphyria and chronic hepatic porphyria. The subtypes with major clinical relevance are porphyria cutaneatarda and acute intermittent porphyria. Diagnosing porphyrias may be quite difficult, as there is significant overlapping between clinical and biochemical findings. The diagnosis depends on the measurement of urinary and fecal porphyrins, enzymatic analysis of erythrocytes and, eventually, analysis of mutations. The main purpose of this article is to make a review of porphyrias, with emphasis on diagnosis and treatment of its several subtypes...

Talidomida no tratamento de angiodisplasias intestinais em paciente com síndrome CREST: relato de caso e revisão da literatura / Thalidomide as a treatment of intestinal angiodisplastic lesions in a patient with CREST syndrome: case report and literature review

A anemia ferropriva grave secundária à hemorragia digestiva por angiodisplasias intestinais representa um grande desafio terapêutico. Comumente, as ectasias vasculares são múltiplas e dispersas ao longo do intestino, limitando a eficácia do tratamento hemostático local. Nos últimos anos houve significativo avanço no tratamento anti-angiogênico sistêmico das angiodisplasias intestinais, sendo talidomida a droga mais empregada para tal fim. Relatamos o caso de uma paciente de 49 anos com angiodisplasias intestinais secundárias a síndrome CREST (Calcinose, Raynaud, Dismotilidade Esofágica, Esclerodactilia e Telangiectasias). A paciente apresentava quadro de melena recorrente e alta necessidade transfusional, e não obteve resposta clínica após realização de enteroscopia e eletro-coagulação das lesões com plasma de argônio. Após a introdução de talidomida 100mg ao dia, a paciente evoluiu de forma bastante satisfatória. O caso apresentado neste texto, além de demonstrar sucesso da talidomida no tratamento de angiodisplasias intestinais refratárias à eletro-coagulação com plasma de argônio, também revela eficácia da droga na situação específica da síndrome CREST. Tal fato pode ser de grande valia quando da abordagem de hemorragia intestinal por angiodisplasias nesses pacientes, representando nova opção terapêutica...

The severe ferropenic anemia secondary to digestive bleeding due to intestinal angiodisplastic lesions represents a great challenge. Commonly, angiodisplastic lesions are multiples and disperse through the intestine and that fact limits local treatments. Over the last years, there was a great advance in the antiangiogenic treatment of intestinal angiodisplastic lesions and thalidomide was the most employed drug for this purpose. We report a case of a 49 year-old patient with intestinal angiodisplastic lesions due to CREST syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia). The patient presented repeated episodes of digestive bleeding and did not achieve clinical improvement after enteroscopy and argon plasma coagulation. The treatment consisting of the introduction of thalidomide 100mg per day demonstrated success. The case presented in this text reveals success in the use of thalidomide in the treatment of intestinal angiodisplastic lesions, probably representing a new therapeutic option...

Estudo da deformabilidade eritrocitária através da ectacitometria / Study of erythrocyte deformability through ecktacytrometry

A deformabilidade eritrocitária foi estudada através da ectacitometria em uma série de pacientes portadores de esferocitose hereditária e de anemia falciforme e, comparados com os achados de indivíduos normais. A ectacitometria foi realizada no aparelho LORCA (Laser assisted rotational cell analyser - R & R Mechatronics, Holanda). Observamos diminuiçäo da deformmbilidade celular, medida através do índice de elongaçäo (ou de deformabilidade) em todos os pacientes portadores de esferocitose hereditária e de anemia falciforme. O grau de diminuiçäo da deformabilidade esteve relacionado à maior gravidade clínica, havendo correlaçäo com a porcentagem de células microcíticas e hiperdensas, verificado na esferocitose hereditária e também na anemia falciforme. A perda de material da membrana, com consequente alteraçäo da geometrial celular, desidrataçäo celular e aumento da viscosidade citoplasmática, concorrem para a diminuiçäo da deformabilidade observada na esferocitose hereditária. Na anemia falciforme a diminuiçäo da deformabilidade está relacionada ao aumento da densidade celular, secundária às características da hemoglobina S, à desidrataçäo celular e a danos da membrana eritrocitária