Factors related to the readiness of Brazilian chronic pediatric patients to transition to care in adult clinics

Abstract Objective Advances in medicine have increased the life expectancy of pediatric patients with chronic illnesses, and challenges with the guided transition of adolescents and young adults from pediatric clinics to adult clinics have grown. The aim of this study was to better understand readiness and factors related to this transition process in Brazil. Method In this cross-sectional study of 308 patients aged from 16 to 21 years under follow-up in pediatric specialties, the degree of readiness for transition was assessed using the Transition Readiness Assessment Questionnaire (TRAQ) and its domains. Associations with demographic data, clinical data, socio-economic level, medication adherence, family functionality, and parental satisfaction with health care were evaluated. Results The median TRAQ score was 3.7 (3.2 - 4.2). Better readiness was associated with female patients, socio-economic class A-B, current active employment, higher level of education, not failing any school year, attending medical appointments alone, functional family, and a good knowledge of disease and medications. A low correlation was observed between TRAQ and age. TRAQ presented good internal consistency (alpha-Cronbach 0.86). In the multiple linear regression, TRAQ score showed a significant association with female gender, advanced age, socio-economic class A-B, better knowledge of disease and medications, and independence to attend appointments alone. Conclusion TRAQ instrument can guide healthcare professionals to identify specific areas of approach, in order to support adolescents with chronic disease to set goals for their own personal development and improve their readiness to enter into the adult healthcare system. In this study, some factors were related to better TRAQ scores.

Sickle cell anemia: hierarchical cluster analysis and clinical profile in a cohort in Brazil

Abstract Introduction Sickle cell anemia is a monogenic disorder caused by a mutation in the β-hemoglobin gene, resulting in sickle hemoglobin that can polymerize. Presentation and clinical course have significant inter-individual variability and classifying these patients for severity is a challenge. Methods We applied hierarchical clusters with 10 routine laboratory tests to understand if this grouping could be associated with clinical manifestations. We included 145 adult homozygous patients (SS) at an outpatient clinic in a retrospective study. Results We found five clusters by counting those that had been differentiated by unconjugated bilirubin, reticulocytes, LDH, leukocytes, lymphocytes and monocytes. When comparing groups to clinical findings, the clusters were different only for liver abnormality. Cluster 3 had the lower median of reticulocytes, LDH, leukocytes, lymphocytes and monocytes and a higher percentage of patients under treatment. Clusters 4 and 5 had higher frequencies of liver impairment and higher medians of reticulocytes, LDH, leukocytes, lymphocytes and monocytes. Hemolysis and inflammation seemed to influence the grouping. Conclusion In our study, cluster analysis showed five groups that exhibited different degrees of inflammation and hemolysis. When comparing clinical data, the result was different only for the criteria of liver abnormality.

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.

Quality of life in adults with sickle cell disease: an integrative review of the literature / Cualidad de vida en adultos con enfermedad falciforme: revisión integradora de la literatura / Qualidade de vida em adultos com doença falciforme: revisão integrativa da literatura

ABSTRACT Objective: To identify the available evidence in the literature on health-related quality of life in adults with sickle cell disease. Method: integrative review of MEDLINE, CUMED, LILACS and SciELO databases, from articles developed in this area, published between 2005 and 2015, in English, Portuguese or Spanish. Results: 22 articles were included, six scales were used to evaluate health-related quality of life scores: three generic and three specific. No specific scale for adults with sickle cell disease has been adapted to Brazilian Portuguese so far. Patients affected by frequent painful crises, with low adherence to treatment, had a compromised quality of life. Conclusion: Selected studies have shown that patients with sickle cell disease have worse scores than the general population. These indicators should be instrumental to the nurse in the proposal of interventions and strategies of assistance and socio-educational, with a view to improving the quality of life of this clientele.

RESUMEN Objetivo: Identificar las evidencias disponibles en la literatura sobre cualidad de vida relacionada a la salud en adultos con enfermedad falciforme. Método: revisión integradora en las bases de datos MEDLINE,CUMED,LILACS y SciELO, de artículos provenientes de estudios desarrollados en esta temática, publicados entre 2005 y 2015, en inglés, portugués o español. Resultados: fueron incluidos 22 artículos, siendo utilizadas seis escalas para evaluar las puntuaciones de cualidad de vida relacionada a la salud: tres genéricas y tres específicas. Ninguna escala específica para adultos con enfermedad falciforme fue adaptada para el portugués brasileño hasta el momento. Pacientes acometidos por crisis dolorosas frecuentes, con baja adhesión al tratamiento, presentaron comprometimiento de la cualidad de vida. Conclusión: Los estudios seleccionados evidenciaron que los pacientes con enfermedad falciforme tienen peores puntuaciones que la población en general. Esos indicadores deberían instrumentalizar el enfermero en la proposición de intervenciones y estrategias asistenciales y socioeducativas, con vistas a mejorar la cualidad de vida de esta clientela.

RESUMO Objetivo: Identificar as evidências disponíveis na literatura sobre qualidade de vida relacionada à saúde em adultos com doença falciforme. Método: revisão integrativa nas bases de dados MEDLINE, CUMED, LILACS e SciELO, de artigos provenientes de estudos desenvolvidos nesta temática, publicados entre 2005 a 2015, em inglês, português ou espanhol. Resultados: foram incluídos 22 artigos, sendo utilizadas seis escalas para avaliar os escores de qualidade de vida relacionada à saúde: três genéricas e três específicas. Nenhuma escala específica para adultos com doença falciforme foi adaptada para o português brasileiro até o momento. Pacientes acometidos por crises dolorosas frequentes, com baixa adesão ao tratamento, apresentaram comprometimento da qualidade de vida. Conclusão: Os estudos selecionados evidenciaram que os pacientes com doença falciforme têm piores escores do que a população em geral. Esses indicadores deveriam instrumentalizar o enfermeiro na proposição de intervenções e estratégias assistenciais e socioeducativas, com vistas a melhorar a qualidade de vida desta clientela.

Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence / Pacientes com doença falciforme são frequentemente excluídos dos benefícios do screening com doppler transcraniano para avaliação do risco de acidente vascular cerebral, apesar de evidência extensa e convincente

ABSTRACT Transcranial doppler (TCD) is a strategic component of primary stroke prevention in children with sickle cell disease (SCD). This study was conducted to examine the TCD characteristics of children with SCD in nine different medical centers in Brazil. Methods: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. Results: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years) were evaluated with TCD for the first time. Conclusions: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.

RESUMO Doppler transcraniano (DTC) é um componente estratégico da prevenção primária do acidente vascular cerebral (AVC) em crianças com doença falciforme (DF). Este estudo foi realizado para examinar as características do DTC de crianças com DF em nove centros médicos diferentes no Brasil. Métodos: DTC foi realizado de acordo com o protocolo de Stroke Prevention Trial in Sickle Cell Anemia Protocol (STOP). Resultados: Dos 396 pacientes avaliados, 69,5% eram homozigotos para hemoglobina SS. DTC foi anormal em 4,8%, condicional em 12,6%, inadequado em 5,3% e anormalmente baixo em 1%. As máximas velocidades de fluxo médio foram 121 ± 23,83cm/s e 124 ± 27,21 cm/s nas artérias cerebrais media esquerda e direita, respectivamente. Um total de 28,8% dos pacientes (média de 9,19 ± 5,92 anos) foram avaliados com o DTC pela primeira vez. Conclusões: Pacientes com DF foram avaliados com DTC numa idade considerada avançada, o que representa uma importante oportunidade perdida para a prevenção de AVC nessa população. Uma vez que a triagem com DTC em pacientes com DF é essencial para detectar aqueles com alto risco de AVC, recomenda-se que essa triagem seja amplamente disponível no país.

The relationship between genotype, psychiatric symptoms and quality of life in adult patients with sickle cell disease in São Paulo, Brazil: a cross-sectional study / A relação entre genótipo, sintomas psiquiátricos e qualidade de vida em pacientes adultos com doença falciforme em São Paulo, Brasil: um estudo transversal

CONTEXT AND OBJECTIVE: Health-related quality of life (HRQoL) may be worsened in sickle cell patients due to the presence of psychiatric disorders. The aims of this study were to describe the psychiatric symptoms in Brazilian sickle cell patients and to evaluate the relationship of these symptoms to the genotype of the disease and the subject's HRQoL. DESIGN AND SETTING: Cross-sectional study conducted at the hematology outpatient clinic, Hospital São Paulo. METHODS: Adult patients with sickle cell disease completed the Medical Outcome Study - Short Form 36 and the Patients' Health Questionnaire. Clinical data were gathered from their medical files. Linear regression models were developed to study the dependency of HRQoL domains on the genotype controlling for psychiatric symptoms. RESULTS: In the study period, 110 patients were evaluated. The most frequent psychiatric symptom was depression (30%), followed by anxiety (12.7%) and alcohol abuse (9.1%). Patients with the more severe genotype (SS and Sβthal0) showed lower scores for the "general health" and "role-physical" HRQoL domains, without interference from psychiatric symptoms. In the "role-physical" domain, the more severe genotype operated as a protective factor for HRQoL (β = 0.255; P = 0.007). CONCLUSION: The more severe genotypes worsened HRQoL in two domains of physical health (general health and role-physical), but they did not have any influence on mental health, thus suggesting that physicians should be more attentive to aspects of HRQoL relating to the functionality of sickle cell disease patients, so as to be aware of the limitations that these patient live with.

CONTEXTO E OBJETIVO: A qualidade de vida relacionada à saúde (QVRS) pode ser piorada em pacientes com doença falciforme na presença de transtornos psiquiátricos. O objetivo deste estudo é descrever a sintomatologia psiquiátrica presente no paciente brasileiro com doença falciforme e avaliar a relação desses sintomas com o genótipo da doença e a QVRS do sujeito. TIPO DE ESTUDO E LOCAL: Estudo com delineamento transversal, realizado no ambulatório de Hematologia do Hospital São Paulo. MÉTODOS: Adultos com doença falciforme responderam ao Questionário de Qualidade de Vida (SF-36) e ao Questionário sobre a Saúde do Paciente (PHQ). Dados clínicos foram obtidos no prontuário médico. Modelos de regressão linear foram desenvolvidos para estudar a dependência dos domínios de QVRS no genótipo com controle para sintomas psiquiátricos. RESULTADOS: No período do estudo, 110 pacientes foram avaliados. O sintoma psiquiátrico mais frequente foi o depressivo (30%), seguido do ansioso (12,7%) e de abuso de álcool (9,1%). Os pacientes com genótipo mais grave (SS e S βthal0) apresentaram menores médias nos domínios de QVRS de "saúde geral" e de "aspectos físicos", sem interferência dos sintomas psiquiátricos. No domínio "aspectos físicos", o genótipo mais grave funcionou como fator protetor da QVRS (β = 0,255; P = 0,007). CONCLUSÃO: Os genótipos mais graves pioraram a QVRS em dois domínios do componente físico ("aspectos físicos" e "saúde geral"), mas não influenciaram o componente mental, sugerindo que o médico deve estar atento aos aspectos da QVRS relacionados com a funcionalidade do portador da doença falciforme, conhecendo as limitações com as quais o paciente convive.

Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia

BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels.METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests.RESULTS:Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls.CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.

Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia

Objectives: To analyze the frequency of βS-globin haplotypes and alpha-thalassemia, and their influence on clinical manifestations and the hematological profile of children with sickle cell anemia. Method: The frequency of βS-globin haplotypes and alpha-thalassemia and any association with clinical and laboratorial manifestations were determined in 117 sickle cell anemia children aged 3–71 months. The confirmation of hemoglobin SS and determination of the haplotypes were achieved by polymerase chain reaction-restriction fragment length polymorphism, and alpha-thalassemia genotyping was by multiplex polymerase chain reaction (single-tube multiplex-polymerase chain reaction). Results: The genotype distribution of haplotypes was 43 (36.7%) Central African Republic/Benin, 41 (35.0%) Central African Republic/Central African Republic, 20 (17.0%) Rare/atypical, and 13 (11.1%) Benin/Benin. The frequency of the α3.7 deletion was 1.71% as homozygous (−α3.7/−α3.7) and 11.9% as heterozygous (−α3.7/αα). The only significant association in respect to haplotypes was related to the mean corpuscular volume. The presence of alpha-thalassemia was significantly associated to decreases in mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte count and to an increase in the red blood cell count. There were no significant associations of βS-globin haplotypes and alpha-thalassemia with clinical manifestations. Conclusions: In the study population, the frequency of alpha-thalassemia was similar to published data in Brazil with the Central African Republic haplotype being the most common, followed by the Benin haplotype. βS-globin haplotypes and interaction between alpha-thalassemia and sickle cell anemia did not influence fetal hemoglobin concentrations or the number of clinical manifestations...

Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables / Anemia na doença inflamatória intestinal: prevalência, diagnóstico diferencial e associação com variáveis clínicas e laboratoriais

CONTEXT AND OBJECTIVES: Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1) determine the prevalence of anemia among patients with inflammatory bowel disease; 2) investigate whether routine laboratory markers are useful for diagnosing anemia; and 3) evaluate whether any association exists between anemia and clinical/laboratory variables. DESIGN AND SETTING: Cross-sectional at a federal university. METHODS: 44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment) and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid) were investigated. RESULTS: Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6%) and ulcerative colitis (76.7%). Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index. CONCLUSIONS: Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index. .

CONTEXTO E OBJETIVOS: Anemia é a mais frequente complicação extraintestinal na doença inflamatória intestinal. Este estudo objetivou: 1) determinar a prevalência de anemia em portadores de doença inflamatória intestinal; 2) investigar se os marcadores laboratoriais de uso rotineiro são úteis para o diagnóstico da anemia; 3) avaliar se existe associação entre anemia e variáveis clínico-laboratoriais. TIPO DE ESTUDO E LOCAL: Estudo transversal em uma universidade federal. MÉTODOS: Foram avaliados 44 pacientes ambulatoriais com doença de Crohn e 55 com retocolite ulcerativa. Foram investigados aspectos clínicos (índice de atividade da doença, localização da doença e tratamento farmacológico) e laboratoriais (hemograma, ferrocinética, vitamina B12 e ácido fólico). RESULTADOS: Anemia e/ou anormalidades na ferrocinética estavam presentes em 75% dos pacientes com doença de Crohn e em 78,2% dos pacientes com retocolite. Anemia foi observada em 20,5% do grupo com doença de Crohn e em 23,6% do grupo com retocolite. Anemia por deficiência de ferro predominou entre os pacientes com doença de Crohn (69,6%) e com retocolite (76,7%). Anemia de doença crônica associada à anemia ferropriva estava presente em 3% dos pacientes com doença de Crohn e em 7% daqueles com retocolite. Na retocolite, a anemia estava associada com o índice de atividade da doença. CONCLUSÕES: A maioria dos pacientes apresentava alterações na ferrocinética com ou sem anemia, principalmente decorrente da ferropenia. O diagnóstico diferencial entre os dois tipos mais prevalentes de anemia foi baseado nos dados clínicos e nos testes laboratoriais de rotina. Anemia estava associada com o índice de atividade na retocolite. .

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.

Diagnóstico diferencial da deficiência de ferro: [revisão] / Differential diagnosis of iron deficiency: [review]

A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.

Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.

Impacto da inflamação na regulação do ferro e deficiência funcional de ferro: [revisão] / Importance of inflammation on iron homeostasis and functional iron deficiency: [review]

Deficiência funcional de ferro (Fe) pode ser definida como o desbalanço entre a quantidade necessária de Fe para a síntese de hemoglobina e o seu suprimento. Ela ocorre na ausência de estoque de Fe, característica da anemia ferropênica (AF), e na presença de bloqueio da homeostasia do Fe, como na anemia da inflamação (AI). Na AI, citocinas e células do sistema retículo-endotelial induzem alterações que interferem em diferentes vias da eritropoese levando à anemia. O bloqueio na mobilização do Fe de estoque pela hepcidina, embora não único, é o mecanismo etiológico mais evidente da AI. A hepcidina, regulador negativo da entrada de Fe no plasma, atua ligando-se à ferroportina, induzindo sua internalização e degradação. Embora a diferenciação entre AF e AI seja relativamente tranquila, pacientes com AI podem cursar com deficiência de Fe associada. O diagnóstico diferencial entre AI e AI com deficiência de Fe tem evidente importância clínica, e novas técnicas laboratoriais têm sido sugeridas para auxiliar neste diagnóstico.

Functional iron deficiency can be defined as an imbalance between the iron needs of the erythroid marrow and iron supply. Iron deficiency occurs in the absence of iron deposits, as in the case of iron deficiency anemia (IDA), or when there is an impaired iron mobilization, such as in anemia of inflammation (AI). Cytokines and cells of the reticuloendothelial system can induce changes in several pathways, interfering in erythropoiesis and causing anemia. The retention of iron within cells of the reticuloendothelial system is due to hepcidin. Although this is not the only mechanism evolved in AI, it is the most important. Hepcidin is a negative regulator of iron entry into the plasma. Hepcidin binds to ferroportin, inducing its internalization and degradation. Differentiation between IDA and AI is relatively easy, but patients with AI can have the association of true iron deficiency. The differential diagnosis of AI and AI with iron deficiency is clinically important and new laboratorial markers can be used to help this differentiation.

Hemoglobinúria paroxística noturna: da fisiopatologia ao tratamento / Paroxysmal nocturnal hemoglobinuria: from physiopathology to treatment

Hemoglobinúria 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.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder, an acquired chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, recurrent infections, neutropenia, thrombocytopenia, and episodes of venous thrombosis. Its clinical course is highly variable. It frequently arises in association with bone marrow failure, particularly aplastic anemia and myelodysplastic syndrome. It is also an acquired thrombophilia, presenting with a variety of venous thrombosis, mainly manifested with intra-abdominal thrombosis, here the major cause of mortality. The triad of hemolytic anemia, pancytopenia, and thrombosis makes a truly unique clinical syndrome of PNH, which was reclassified from a purely acquired hemolytic anemia to a hematopoietic stem cell mutation defect of the phosphatidyl inositol glycanclass-A gene. This mutation results in an early block in the synthesis of glycosylphosphatidylinositol (GPI) anchors, responsible for binding membrane functional proteins. Among these proteins are the complement inhibitors, especially CD55 and CD59, that play a key role in protecting blood cells from complement cascade attack. Therefore, in PNH occurs an increased susceptibility of red cells to complement, and consequently, hemolysis. We here review PNH physiopathology, clinical course, and treatment options, especially eculizumab, a humanized monoclonal antibody that blocks the activation of terminal complement at C5 and prevents formation of the terminal complement complex, the first effective drug therapy for PNH.