ResumoHemoglobinúria paroxística noturna (HPN) é uma anemia hemolítica crônica adquirida rara, de curso clínico extremamente variável. Apresenta-se frequentemente com infecções recorrentes, neutropenia e trombocitopenia, e surge em associação com outras doenças hematológicas, especialmente com síndromes de falência medular, como anemia aplásica e síndrome mielodisplásica. É considerada ainda um tipo de trombofilia adquirida, apresentando-se com tromboses venosas variadas, com especial predileção por trombose de veias hepáticas e intra-abdominais, sua maior causa de mortalidade. A tríade anemia hemolítica, pancitopenia e trombose faz da HPN uma síndrome clínica única, que deixou de ser encarada como simples anemia hemolítica adquirida para ser considerada um defeito mutacional clonal da célula-tronco hematopoética (CTH). A mutação ocorre no gene da fosfaditilinositolglicana classe-A, e resulta no bloqueio precoce da síntese de âncoras de glicosilfosfaditilinositol (GPI), responsáveis por manter aderidas à membrana plasmática dezenas de proteínas com funções específicas. A falência em sintetizar GPI madura gera redução de todas as proteínas de superfície normalmente ancoradas por ela. Dentre elas estão o CD55 e o CD59, que controlam a ativação da cascata do complemento. Assim, na HPN há aumento da susceptibilidade de eritrócitos ao complemento, gerando hemólise. Revisa-se aqui sua fisiopatologia, curso clínico, os tratamentos disponíveis com ênfase para o transplante de células-tronco hematopoéticas alogênicas e para o eculizumab, um anticorpo monoclonal humanizado que bloqueia a ativação do complemento terminal no nível C5 e previne a formação do complexo de ataque à membrana, a primeira droga a demonstrar eficácia no tratamento da HPN. uniterMoS: Resultado de tratamento. Hemoglobinúria paroxística. Revisão. Sintomas clínicos.

SummaryErythrocytes from sickle cell anaemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells. Oxidative stress seems to primarily affect the membrane and results in haemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants. To evaluate the impact of vitamins C (VitC) and E (VitE) supplementation in SCA patients, patients over 18 years were randomly assigned to receive VitC 1400 mg + VitE 800 mg per day or placebo orally for 180 d. Eighty-three patients were enrolled (44 vitamins, 39 placebo), median age 27 (18-68) years, 64% female. There were no significant differences between the two groups regarding clinical complications or baseline laboratorial tests. Sixty percent of the patients were VitC deficient, 70% were VitE deficient. Supplementation significantly increased serum VitC and E. However, no significant changes in haemoglobin levels were observed, and, unexpectedly, there was a significant increase in haemolytic markers with vitamin supplementation. In conclusion, VitC + VitE supplementation did not improve anaemia and, surprisingly, increased markers of haemolysis in patients with SCA and S-b 0 -thalassaemia. The exact mechanisms to explain this findings and their clinical significance remain to be determined.

Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.

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Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disease of hematopoietic cells due to acquired mutations in the phosphatidylinositol glycan class A (PIG-A) gene, which is required for glycosylphosphatidylinositol (GPI) anchor biosynthesis. This leads to partial or complete absence of all GPI-linked proteins, who are complement regulatory proteins, resulting in an increased sensitivity of the red blood cells to the action of complement. PNH is characterized by signs and symptoms related to intravascular hemolysis, hypercoagulability state, and varying degrees of medullary insufficiency. The anti-complement therapy radically changed the PNH patients outcomes. However, there are little data on the clinical characteristics of PNH in Latin American countries. Methods: We performed a retrospective analysis of 109 patients with PNH clone followed from January 1987 until July 2019 in two Brazilian centers: Universidade Federal de Sao Paulo and Hospital Sirio Libanes (Sao Paulo-Brazil). Most patients (88%) were evaluated while the others had lost follow up or died and data was obtained from their medical reports. Patients were separated into 3 groups: classical PNH (n=44) PNH associated with other bone marrow disorder(n=12), and subclinical PNH, defined as PNH clone (at least 0.01% of cells with PNH clone) associated with another bone marrow disorder (n=53, aplastic anemia in 95% of cases). Median follow up was 60 months (range: 3-394). Results: Median age at diagnosis was 41 years (range: 18-81), and 51% were male. Among the 56 patients with hemolytic PNH, 86% had fatigue, 66% hemoglobinuria, 45% abdominal pain and 16% dysphagia. Venous thromboembolism was observed in 14 cases (25%), with abdominal thrombosis in 7 cases (50%). Seven patients (13%) had arterial thrombosis (stroke or transient ischemic attack). Only 5 patients (10%) in the hemolytic group had acute renal failure and needed dialysis therapy due to a hemolytic crisis, but progressed to recovery of renal function after the event. No patient in this series had moderate or severe chronic kidney disease. Most hemolytic patients (73%) were treated with eculizumab, with a median time from diagnosis to the start of eculizumab of 25 months (range: 2-275). All eculizumab-treated patients had significant reduction in intravascular hemolysis with lactate dehydrogenase (LDH) normalization. Most had significant improvement in anemia, with increase in the median hemoglobin from 9.1 g/dL before treatment to 11.7 g/dL after eculizumab. The vast majority (94%) became transfusion-independent. Overall survival (OS) at 5 years was 100% at 5 years for classical PNH (n=44), 89% for subclinical PNH (n=53) and 71% for PNH associated with another bone marrow disease (n=12). Conclusion: The clinical data and the distribution of the three subtypes of PNH in this study in this large series of Brazilian PNH patients were similar to other published series, except for a lower frequency of venous or arterial thrombosis in hemolytic patients before eculizumab treatment and a lower frequency of chronic kidney disease in our series. We also confirmed in our series the efficacy of eculizumab in controlling hemolysis and PNH-related complications and death risk. Disclosures No relevant conflicts of interest to declare.