Pulmonary hypertension is becoming a recognized complication of the hereditary and acquired haemolytic anaemias, associated with a poor prognosis. Recently we reported that patients with paroxysmal nocturnal haemoglobinuria (PNH) have high levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with both right and left ventricular dysfunction and cardiac dysfunction. In the current study we evaluated a cohort of patients (N = 29) with haemolytic PNH for elevated pulmonary artery systolic pressure and cardiac function by Doppler-echocardiography. Of the 29 patients, eight were further studied using cardiac magnetic resonance imaging (MRI), as well as two additional patients (number of patients studied using cardiac MRI = 10). Plasma from the first cohort (N = 29) demonstrated intravascular haemolysis associated with a 12-fold increase in median nitric oxide (NO) consumption when compared with healthy volunteers (P < 0·001). Doppler echocardiography demonstrated normal left ventricular function and elevated pulmonary artery systolic pressure in 41% of patients. Cardiac MRI from the second cohort (N = 10) demonstrated depressed right ventricular function in 80% of PNH patients tested, and 60% had findings suggestive of subclinical small pulmonary emboli. Together, these data suggest a high prevalence of haemolysis-associated NO scavenging, Doppler-estimated systolic pulmonary hypertension, and depressed right ventricular function in patients with PNH.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1998. / Typescript. Bibliography: leaves 118-128.

This study focuses on the way in which learners living with epilepsy, who attend mainstream schools in the rural areas of the Limpopo Province, experience epilepsy. The results of the study indicate that the needs of learners with epilepsy are not well-catered for in mainstream schools. They often experience fear, anxiety, humiliation, ostracisation, name-calling, scape-goating, blaming and suspicion. Recommendations were made regarding the measures which should be taken to address the needs of rural children living with epilepsy. These recommendations could be used by teachers and the Department of Education. / Educational Studies / M.Ed. (Guidance and Councelling)

No description available.

No description available.

This study focuses on the way in which learners living with epilepsy, who attend mainstream schools in the rural areas of the Limpopo Province, experience epilepsy. The results of the study indicate that the needs of learners with epilepsy are not well-catered for in mainstream schools. They often experience fear, anxiety, humiliation, ostracisation, name-calling, scape-goating, blaming and suspicion. Recommendations were made regarding the measures which should be taken to address the needs of rural children living with epilepsy. These recommendations could be used by teachers and the Department of Education. / Educational Studies / M.Ed. (Guidance and Councelling)

Made available in DSpace on 2014-07-29T15:29:12Z (GMT). No. of bitstreams: 1 Dissertacao Gabriella A Alvarenga.pdf: 1532935 bytes, checksum: d0ff0c9eaffd1c72955c2eee2058c498 (MD5) Previous issue date: 2010-10-18 / Dissertation built modality scientific article. In the first article submitted to "Journal of Otolaryngology" with the title benign paroxysmal positional vertigo without nystagmus: diagnosis and treatment, there was a literature review, using the following keywords: "dizziness / vertigo, diagnosis / diagnosis, therapeutic / therapeutical approaches. " Scientific publications are included in the period 2001-2009 in Portuguese, English and German. We found nine papers dealt with BPPV without nystagmus, whose diagnosis was based exclusively on clinical history and physical examination. The treatment of BPPV without nystagmus was made by Epley maneuvers, Semont, discharge modified for posterior semicircular canal and Brandt-Daroff exercises. All show that 50% to 97.1% of patients with BPPV without nystagmus, had remission of symptoms, while patients with BPPV nystagmus with remission of symptoms ranged from 76% to 100%. Hence one can conclude that the differences may not be significant, which demonstrates the need for further studies on BPPV without nystagmus. In the second paper, Functional Capacity of Elderly with benign paroxysmal positional vertigo, compared the functional capacity among elderly patients with BPPV and elderly without clinical diagnosis of BPPV and that / or dizziness or vertigo, identifying the physical activities of daily living and instrumental activities of daily living in elderly people in both the Group of Elderly with BPPV (EBPPVG) and Control Group (CG). This is a cross-sectional study, case-control study in Hospital Geral de Goiânia (HGG), with the participation of 14 elderly patients with a diagnosis of BPPV and the Programa de Gerontologia Social / Universidade Aberta à Terceira Idade (UNATI) from the Pontificia Universidade Católica de Goiás (PUC-GO), with the participation of 13 subjects without dizziness or vertigo and / or clinical diagnosis was of BPPV. Functional capacity was assessed by the subscale of the Functional Assessment Questionnaire Brazilian Multidimensional Functional Capacity / Operating Older American Resources and Services Multidimensional Functional Assessment Questionnaire (BOMFAQ/OARS), verifying that the difficulty in performing 15 activities of daily living (ADL), eight physical activities of daily living (AFVD): throw / out of bed, eating, combing hair, walk on the plane, bathing, dressing, going to the bathroom in time and trimming toenails, and seven instrumental activities of living daily living (IADL): climbing stairs (one flight), doctor-on time, walk close to home, shopping, preparing meals, driving out and do house cleaning. Arrived at the following conclusions: a) elderly people with BPPV showed a statistically significant lower functional capacity than subjects without this diagnosis, b) in EBPPVG, the average number of daily activities (physical and instrumental), those with difficulty was 6.53 with a maximum of 11 activities committed while in the CG, the average impairment was 0.86 with a maximum of 4 activities referred with difficulty in performing c) EBPPVG affected performance in 13 activities of daily living, including physical seventh floor in the plan, bathing, dressing, combing hair, going to the bathroom in time, bedtime and getting up from bed or chair and cut nails feet, and 6 which are instrumental, climbing stairs, walking around the house, shopping, preparing meals, driving out and do house cleaning in the comparison between groups, d) Activities that were cited as the most difficult among the elderly were similar in both groups. However, the degree of impairment, characterized in: without commitment (when the elderly did not report any difficulty in any of the 15 evaluated ADL), mild (1 to 3 activities impaired), moderate (4-6 impaired activities) and severe (for seven or more impaired activities) was significantly higher in EBPPVG, where 7 (50%) showed severe impairment in ADL performance. / Dissertação construída na modalidade artigo científico. No primeiro artigo enviado para a Revista Brasileira de Otorrinolaringologia com o título Vertigem Posicional Paroxística Benigna sem nistagmo: diagnóstico e tratamento, realizou-se uma revisão da literatura, utilizando-se os seguintes descritores: vertigem/vertigo, diagnóstico/diagnosis, conduta terapêutica/ therapeutical approaches , palavras e assunto vertigem , nistagmo , VPPB , VPPB sem nitagmo , VPPB subjetiva . As publicações científicas incluídas são do período de 2001 a 2009 nos idiomas português, inglês, espanhol e alemão. Foram encontrados nove artigos que abordam a VPPB sem nistagmo, cujo diagnóstico foi baseado exclusivamente na história clínica e no exame físico. O tratamento da VPPB sem nistagmo foi realizado pelas manobras de Epley, Sémont, liberatória modificada para canal semicircular posterior e exercícios de Brandt-Daroff. Todos evidenciam que de 50% a 97.1% dos pacientes com VPPB sem nistagmo, tiveram remissão dos sintomas, enquanto nos pacientes com VPPB com nistagmo a remissão dos sintomas variou de 76% a 100%. Conclui-se que as diferenças podem não ser significativas, o que demonstra a necessidade de mais estudos sobre a VPPB sem nistagmo. No segundo artigo, com o título Capacidade Funcional de Idosos com Vertigem Posicional Paroxística Benigna, comparou-se a capacidade funcional entre idosos com VPPB e idosos sem diagnóstico clínico referido de VPPB e/ou queixa de tontura ou vertigem, identificando as atividades físicas de vida diária e as atividades instrumentais de vida diária comprometidas nos idosos tanto no Grupo de Idosos com VPPB (GIVPPB) quanto no Grupo Controle (GC). Trata-se de um estudo transversal, analítico, observacional e comparativo, realizado no Hospital Geral de Goiânia (HGG), com a participação de 12 idosos com diagnóstico de VPPB e no Programa de Gerontologia Social/ Universidade Aberta á Terceira Idade (UNATI) da Pontifícia Universidade Católica de Goiás (PUC-GO), com a participação de 13 idosos sem queixa de tontura ou vertigem e/ou diagnóstico clínico referido de VPPB. A capacidade funcional foi avaliada por meio da subescala funcional do Questionário Brasileiro da Avaliação Multidimensional de Capacidade Funcional/Brazilian Older American Resources and Services Multidimensional Functional Assessment Questionaire (BOMFAQ/OARS), verificando a dificuldade referida na realização de 15 atividades de vida diária (AVD), sendo oito atividades físicas de vida diária (AFVD): deitar/levantar da cama, comer, pentear cabelo, andar no plano, tomar banho, vestir-se, ir ao banheiro em tempo e cortar unhas dos pés, e sete atividades instrumentais de vida diária (AIVD): subir escada (um lance), medicar-se na hora, andar perto de casa, fazer compras, preparar refeições, sair de condução e fazer limpeza de casa. Chegou-se às seguintes conclusões: a) idosos com VPPB apresentam uma capacidade funcional estatisticamente significativa menor do que idosos sem este diagnóstico; b) no GIVPPB, o número médio de atividades de vida diária (físicas e instrumentais), referidas com dificuldade foi de 6,53 com o máximo de 11 atividades comprometidas, enquanto no GC, a média de comprometimento foi de 0,86 com o máximo de 4 atividades referidas com dificuldade no desempenho; c) A VPPB prejudicou o desempenho em 13 atividades de vida diária, 7 físicas incluindo andar no plano, tomar banho, vestir-se, pentear-se, ir ao banheiro em tempo, deitar e levantar-se da cama ou cadeira e cortar unhas dos pés; e 6 instrumentais quais sejam, subir escada, andar perto de casa, fazer compras, preparar refeições, sair de condução e fazer limpeza da casa na comparação entre os grupos; d) As atividades que foram referidas como mais difíceis entre os idosos, foram similares em ambos os grupos. Contudo, o grau de comprometimento, caracterizado em: sem comprometimento (quando o idoso não referia dificuldade em nenhuma das 15 AVD avaliadas), leve (de 1 a 3 atividades comprometidas), moderado (de 4 a 6 atividades comprometidas) e severo (de sete ou mais atividades comprometidas) foi significativamente maior no GIVPPB, onde 7(50%) evidenciaram severo comprometimento no desempenho das AVD.

Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2017-12-27T12:14:00Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese - Gabriella Assumpção Alvarenga Schimchak - 2017.pdf: 1840051 bytes, checksum: 09ab566a12fa9b2b1ab4c9c52b7a75d2 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-12-28T09:41:10Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese - Gabriella Assumpção Alvarenga Schimchak - 2017.pdf: 1840051 bytes, checksum: 09ab566a12fa9b2b1ab4c9c52b7a75d2 (MD5) / Made available in DSpace on 2017-12-28T09:41:10Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese - Gabriella Assumpção Alvarenga Schimchak - 2017.pdf: 1840051 bytes, checksum: 09ab566a12fa9b2b1ab4c9c52b7a75d2 (MD5) Previous issue date: 2017-06-05 / Thesis held in the papers format. The first article is a systematic review that aimed to investigate the relationship between BPPV and falls (with and without fracture). The review was carried out independently by two researchers, using the combined descriptors in English, Portuguese and Spanish, "vertigo" and "elderly" and "accidental falls"; "benign paroxysmal positional vertigo" and "accidental falls"; in the Virtual Health Library and United States National Library of Medicine (PubMED) databases, being the last search in August 2016. Six scientific papers were selected. The results showed that there were double falls in the elderly with the diagnosis of BPPV and this the relationship increased with advancing age. There was evidence of a decrease in episodes of falls above 60% of the elderly who were treated for BPPV. In elderly people with more than one cause for dizziness, BPPV can not be considered as an independent risk factor for falls. However, in the hospital environment, the relationship between BPPV and falls was not observed when the investigation was performed from the hip fracture. However, when the study included elderly patients hospitalized for various consequences of falls, BPPV could be identified in more than 50% of the patients. It can be concluded that BPPV is associated with falls. The second article, whose primary objective was to evaluate dizziness in the elderly in the primary care for the recognition of BPPV and the secondary one, to analyze the association between dizziness and BPPV with falls. It was a cross-sectional study of 298 diabetic and / or hypertensive elderly individuals enrolled in the Hypertensive and Diabetic Monitoring System of the Basic Family Health Unit of the Madre Germana II neighborhood of Goiânia, Goiás. The evaluation was carried out at the residence of the elderly, including the Mini Mental State Examination, sociodemographic profile, record of self-reported health conditions with emphasis on reporting dizziness and / or vertigo and record of falls in the last 12 months. The elderly who reported dizziness and/or vertigo were revisited for functional otoneurological evaluation for BPPV, using the Dix Hallpike test for the posterior and anterior semicircular canals and the Supine Roll test for the horizontal semicircular canal. The study included 150 elderly individuals with a mean age of 69.7 (+/- 7.36), the majority of them were female. Dizziness was reported by 50 elderly (33.3%). Among the 50 patients who reported dizziness, 19 had objective and subjective BPPV (38.8%). There was association between the complaint of dizziness and falls (p = 0.05), which did not occur with BPPV. The assessment of dizziness and BPPV can be performed in the home of the elderly in primary care. This proactive approach can help prevent falls because dizziness has increased the chances of the elderly falling. Although elderly people who presented objective or subjective BPPV did not increase their chances of falls, the identification of this disease, which has a known, effective and financially inexpensive treatment, may lead to the resolution of this clinical condition. / Tese construída na forma de artigos científicos. O primeiro artigo é uma revisão sistemática que objetivou investigar a relação entre VPPB e quedas (com e sem fratura). A revisão foi realizada de forma independente por duas pesquisadoras, utilizando os descritores combinados em inglês, português e espanhol, “vertigem” and “idoso” and “acidentes por quedas"; “vertigem posicional paroxística benigna” and idoso and acidentes por quedas”; vertigem posicional paroxística benigna” and “acidentes por quedas”, nas bases de dados Biblioteca Virtual em Saúde (BVS), United States National Library of Medicine (PubMED), sendo a última busca em agosto de 2016. Foram selecionados seis artigos. Observou-se diversidade metodológica entre os estudos. Quedas ocorreram o dobro de vezes em idosos com o diagnóstico de VPPB e esta relação aumentou com o avanço da idade. Houve evidência de diminuição de episódios de quedas acima de 60% dos idosos que foram tratados da VPPB. Em idosos com mais de uma causa para a tontura, a VPPB não pode ser considerada como fator de risco independente para quedas. Contudo, no ambiente hospitalar, a relação entre VPPB e quedas não foi observada quando a investigação foi realizada a partir da fratura de quadril. No entanto, quando o estudo incluiu idosos internados por consequências diversas de quedas, a VPPB pôde ser identificada em mais de 50% dos pacientes. Pode-se concluir que a VPPB está associada a quedas. O segundo artigo, teve como objetivos, avaliar a tontura em idosos na atenção primária para o reconhecimento da VPPB e analisar a associação entre tontura e VPPB com quedas. Foi um estudo do tipo transversal sendo estudados 298 idosos diabéticos e/ou hipertensos, cadastrados no Sistema de Acompanhamento de Hipertensos e Diabéticos da Unidade Básica de Saúde da Família do bairro Madre Germana II de Goiânia, Goiás. A avaliação foi realizada na residência dos idosos incluindo o Mini Exame do Estado Mental, perfil sociodemográfico, registro das condições de saúde auto referidas com ênfase no relato de tontura e/ou vertigem e registro de quedas nos últimos 12 meses. Os idosos que referiram tontura e/ou vertigem foram revisitados para avaliação funcional Abstract xvi otoneurológica para VPPB, utilizando o teste de Dix Hallpike para os canais semicirculares posterior e anterior e Supine Roll test para o canal semicircular horizontal. Foram incluídos no estudo 150 idosos com média de idade de 69,7(+/-7,36), a maioria do sexo feminino e 26% referiam queda. Tontura foi referida por 33% dos idosos, dentre os quais, 38,8% apresentaram VPPB. Houve associação entre a queixa de tontura e quedas (p=0,05), o que não ocorreu com a VPPB objetiva ou subjetiva. A avaliação da tontura e VPPB pode ser realizada no domicílio de idosos na atenção primária.

L'objectif de mon travail a été d'étudier les bases génétiques de deux maladies du mouvement, les mouvements miroirs congénitaux (CMM) et les dyskinésies paroxystiques kinésigéniques (PKD). Nous avons tout d'abord mis en évidence le deuxième gène impliqué dans les CMM, RAD51, et commencé à explorer quelques hypothèses physiopathologiques. Nous avons ensuite recueilli les ADN de 26 cas index de CMM isolés, et montré que près de 50% d'entre eux avaient un variant possiblement pathogène dans RAD51 ou dans le premier gène de CMM décrit, DCC. Nous avons ensuite écarté l'implication d'un troisième gène possiblement causal, DNAL4, dans 17 cas index. Enfin, nous avons collaboré avec une équipe néo-zélandaise et mis en évidence par séquençage de l'exome un nouveau gène, NTN1, codant pour le ligand de DCC, dans deux familles et un cas sporadique. En ce qui concerne les PKD, nous avons analysé le premier gène impliqué dans cette pathologie, PRRT2, dans une cohorte de 42 cas index. Nous avons ainsi montré que PRRT2 est un gène majeur de PKD dans la population européenne, impliqué dans 65% des cas typiques. Nous avons ensuite contribué à mettre en évidence l'implication de PRRT2 dans la migraine hémiplégique, et effectué une revue de la littérature montrant que les mutations de PRRT2 peuvent être responsables de phénotypes multiples de mouvements anormaux paroxystiques. Nous avons ensuite réalisé un séquençage d'exomes chez une famille et 10 trios, malheureusement sans résultat probant. Enfin, chez deux patients avec PKD atypiques, nous avons mis en évidence des mutations du gène ADCY5, récemment impliqué dans des formes complexes de dyskinésies paroxystiques. / The objective of my work was to study the genetic bases of two movement disorders, congenital mirror movements (CMM) and paroxysmal kinesigenic dyskinesia (PKD). First we uncovered the second gene implicated in CMM, RAD51, and started to explore pathophysiological hypotheses. Then we collected DNA of 26 index cases of isolated CMM, and showed that almost 50% of them had a possibly pathogenic variant in RAD51 or in the first described gene of CMM, DCC. We subsequently ruled out the implication of a possible third gene, DNAL4, in 17 cases. Finally, we collaborated with a team from New Zealand to implicate a novel gene, NTN1, coding for the ligand of DCC, in two families and one sporadic case. Concerning PKD, we analyzed the first causative gene described, PRRT2, in a cohort of 42 index cases. We showed that PRRT2 is a major gene of PKD in the European population, involved in 65% of typical cases. We then contributed to show the implication of PRRT2 mutations in hemiplegic migraine, and conducted a review of the literature concluding that PRRT2 mutations can induce multiple types of paroxysmal disorders. We sequenced the exomes of one family and 10 trios negative for PRRT2, but were unable to uncover another causative gene. Finally, in two patients with atypical PKD, we found mutations in ADCY5, a gene recently implicated in complex forms of paroxysmal dyskinesia.

INTRODUÇÃO: A HPN é uma patologia na qual a atividade do sistema complemento, sem oposição, leva a complicações sistêmicas. Ela é caracterizada por anemia hemolítica adquirida com hemoglobinúria intermitente, falência medular e fenômenos tromboembólicos (TE). A trombose venosa é a sua principal causa de mortalidade, entretanto o seu mecanismo fisiopatológico é apenas parcialmente elucidado. O grande número de pacientes com trombocitopenia dificulta o manejo da profilaxia antitrombótica secundária e primária. Optou-se por evidenciar o desequilíbrio hemostático associado ao clone HPN através de um teste de avaliação global da coagulação. MÉTODOS: Para a detecção do potencial hemostático de cada indivíduo foi utilizado um ensaio fluorogênico de geração de trombina, em amostra de plasma pobre em plaquetas na presença e na ausência de trombomodulina (TM). A eficiência na redução do potencial de trombina endógeno (ETP) e da concentração máxima de trombina (pico) pela TM foi utilizada para a identificação do estado de hipercoagulabilidade. O tempo para o início da geração de trombina (tempo de latência) e para a concentração máxima de trombina foram utilizados para a detecção do fenótipo hemorrágico. Os indivíduos foram categorizados em três grupos: HPN, se clone HPN >= 10%; anemia aplástica idiopática adquirida ou associada a clone < 10%, e normais. Os pacientes e controles foram submetidos a avaliação laboratorial que incluiu pesquisa de trombofilia (TB) e do clone HPN, hemograma, testes habituais de avaliação da hemostasia, e no grupo de pacientes análise bioquímica. Os participantes foram avaliados para a identificação da presença de fatores de risco para TE através de questionário. A análise dos resultados foi realizada em duas fases: a primeira incluiu apenas indivíduos com pesquisa de TB negativa e sem fatores de risco para TE; a segunda, realizada apenas no grupo de pacientes, também incluiu indivíduos em uso de contraceptivo hormonal, diagnóstico de infecção assintomática, evento de TE associado a fator de risco temporário, em período superior a 1 ano da inclusão no estudo, e com pesquisa de TB positiva. Esta última fase da análise teve como objetivo incluir um maior número de pacientes com o diagnóstico destas patologias, de baixa prevalência populacional. RESULTADOS: A presença do clone >= 10% foi associada à ineficiência da ação da TM em reduzir o ETP e o pico. O primeiro, de maior relevância científica e clínica, apresentou correlação positiva e negativa, respectivamente, com a atividade do fator von Willebrand (FvW:RCo) e com níveis plasmáticos de proteína C (PC). O grupo HPN apresentou menor tempo para atingir o pico. Na segunda fase, o tempo de latência apresentou correlação negativa com o número de plaquetas no grupo HPN, e houve correlação positiva do clone com a ineficiência da ação da TM na redução do ETP. CONCLUSÕES: o teste de geração de trombina é eficaz na detecção do fenótipo protrombótico associado ao clone HPN. As correlações encontradas com o FvW:RCo e a PC sugerem que a ativação endotelial e o sistema da PC, respectivamente, podem estar comprometidos. A inflamação secundária à ativação do sistema complemento pode levar à redução de expressão endotelial da TM e do receptor da PC. Entretanto os nossos achados, associados à descrição recente da redução de expressão e de atividade da TM, secundária à depleção de óxido nítrico (em estudos com estatinas), podem justificar a característica agressiva da trombofilia na HPN, e o desenvolvimento de TE mesmo nos pacientes em anticoagulação oral. Os parâmetros que avaliam o \'tempo\' no trombograma (tempo de latência e tempo para o pico) podem auxiliar na identificação do risco hemorrágico eventualmente associado à HPN / INTRODUCTION: PNH is a pathology in which the uncontrolled activity of the complement system leads to systemic complications. The pathology is characterized by an acquired hemolytic anemia with intermittent hemoglobinuria, bone marrow failure and thromboembolic event (TE). Venous thrombosis is the main cause of death, however, its physiopathological mechanism is only partially understood. The large number of patients with thrombocytopenia affects the management of primary and secondary antithrombotic prophylaxis. We chose to demonstrate the hemostatic unbalance associated with PNH clone through a global evaluation of the coagulation test. METHODS: To detect the hemostatic potential, we used a fluorogenic thrombin-generation assay, in platelet-poor plasma, with and without throbomodulin (TM). Analysis of the efficiency of TM in reducing the endogenous thrombin potential (ETP) and of the upper limit of thrombin concentration (peak) was done to identify the hypercoagulable state. Times to initiate thrombin generation (latency time-LT) and for reaching the peak were used to identify hemorrhagic phenotypes. Subjects were divided in three groups: PNH patients (if PNH clone >= 10%), patients with acquired idiopathic aplastic anemia or clone-associated (clone < 10%), and controls. Patients and controls were investigated for thrombophilia (TB) and PNH clone, underwent blood test, and regular exams to evaluate hemostasis. Patients were evaluated for the presence of risk factors for TE through questionnaires. Results were analyzed in two steps: the first included only patients negative for TB and with no risk factors for TE; the second step, done only in patients, included individuals using hormonal contraceptive, diagnosis of any asymptomatic infection, TE associated to temporary risk factors, and which have occurred in a period longer than one year since inclusion in the study, and positive TB. The aim of the second step was to gather the largest possible number of patients in these low prevalence pathologies. RESULTS: The presence of the clone >= 10% was associated with TM inefficiency in reducing the ETP (ETP+TM) and peak. In the first analysis, which had greater clinical relevance, we observed a positive correlation between ETP+TM and the activity of the von Willebrand factor (FvW:RCo), whereas a negative correlation was observed with the levels of protein C (PC). The PNH group presented the shortest time to reach the peak. In the second step of the analysis, the LT showed negative correlation with platelet counts in the PNH group, whereas a positive correlation between the clone and ETP+TM was observed. CONCLUSION: The thrombin-generation assay effectively detects the prothrombotic phenotype associated to PNH. The correlation found with both FvW:RCo and PC suggests that endothelial activation, and the PC system as well, may be deficient in these patients. Secondary inflammation to activation of the complement system may lead to lower endothelial expression of TM and of the PC receptor. However, our findings, together with recent descriptions of a reduced expression of the TM activity secondary to nitric oxide depletion (observed in studies on statin) may explain the aggressive nature of thrombophilia in PNH and the development of TE in these patients, even in those taking oral anticoagulants. The parameters that measure the time of thrombin generation may help identify the hemorrhagic risk that might be associated with PNH