Ce travail porte sur deux thèmes principaux. Le premier est relatif à la drépanocytose et comprend deux études. La première a examiné les connaissances qu’ont 178 hommes et femmes vivant au Bénin sur la maladie, ses causes, ses effets et sa prise en charge. Ils ont répondu à un questionnaire et, leurs réponses ont été comparées à celles d’un groupe d’expert. Il en est ressorti qu’il existait une méconnaissance globale de la maladie, et plus particulièrement de ses symptômes les plus graves et de son traitement. Les résultats révèlent que plus on a un niveau d’éducation élevé, moins on se fait de fausses idées concernant la maladie. En outre, cette méconnaissance était plus accrue chez les personnes se déclarant porteuses du trait génétique (4.83) ou drépanocytaire (5.19) que chez les personnes ayant déclaré ne pas être porteuses (3.72) ou saines (3.62). La deuxième étude a quant à elle cherché à savoir si les 137 personnes interrogées vivant au Bénin, avaient intégré de façon adéquate les règles de transmission génétique de la maladie, en se basant sur la théorie fonctionnelle de la cognition. L’analyse des données a permis de distinguer trois clusters distincts. Dans le premier groupe (n=46), les personnes jugeaient ainsi le risque de transmission de la maladie plus élevé en présence de l’un ou l’autre des deux parents atteints. Dans le deuxième groupe (n=51), le risque était jugé d’autant plus grand que chacun des parents était lui-même gravement atteint. Dans le troisième groupe (n=40), le risque n’avait été jugé élevé qu’en présence des deux parents atteints. Le deuxième thème a donné lieu à une étude, visant à examiner les motifs pouvant sous-tendre un refus d’amputation chez 224 personnes vivant au Bénin, par l’approche de la théorie du renversement. Les résultats montrent que la peur de la perte de l’identité personnelle, la peur des hôpitaux et du personnel médical, la conviction que la chirurgie était inutile, le manque de confiance dans la compétence et le dévouement des médecins, la peur de la perte de l’estime de l’autre et celle de la perte de la force spirituelle, font partie des facteurs principaux pouvant motiver un refus d’amputation. / This thesis focuses on two main themes. The first one is related to sickle cell disease and the second theme is related to limb amputations. For studying the first theme, this research proposes to examine the knowledge of 178 men and women living in Benin, on the disease, its causes, effects and care. They answered a questionnaire and their responses had been compared to those given by an expert group. It had been found that there was an overall lack of awareness on the disease, and especially its most severe symptoms and treatment. The results reveal that the higher level of education they have, the less misconceptions about the disease they have. In addition, this ignorance was increased by people declaring themselves carrying the genetic trait (4.83) or sickle cell (5.19) than those who reported not being carriers (3.72) or healthy (3.62). The second study about the first theme, investigated whether the 137 respondents living in Benin had integrated adequately the rules of inheritance of the disease, based on the functional theory of cognition. Three distinct clusters emerge with data analysis. In the first group (n=46), respondents considered a higher risk of transmission if the one or the other of two parents was/were affected by the disease. In the second group (n=51), the risk was considered even greater as both parents were seriously ill. In the third group (n=40), the risk was considered as high only if both parents were touched. The second theme, Accidents involving physical injury, has motivated a study which aim was to examine the reasons that may underlie a refusal of amputation for 224 people living in Benin, by the approach of the reversal theory. The results show that the fear of losing personal identity, the fear of hospitals and medical staff, the belief that the surgery was unnecessary, a lack of confidence in the competences and dedication of doctors, the fear of losing others esteem and the loss of spiritual strength, are among the main factors motivating a refusal of amputation.

Pregnancy in women with hemoglobinopathy has been associated with an increased risk of adverse pregnancy outcomes. We conducted a historical cohort study using Discharge Abstract Database for the fiscal year 1991-1992 through 2007-2008. We estimated the frequency of pregnant women with hemoglobinopathy and examined their associations with adverse pregnancy outcomes. Women with sickle cell disease are more likely to develop pre-eclampsia and preterm labor, and to undergo cesarean delivery than women with nutritional deficiency anemia, suggesting that there are other mechanisms beyond anemia that may be responsible for an increased risk of adverse pregnancy outcomes. The data suggested a synergistic effect of hemoglobinopathy and pre-eclampsia on preterm labor and cesarean delivery. Prediction models for pre-eclampsia, preterm labor and cesarean delivery were created and internally validated for women with hemoglobinopathy, with satisfactory discrimination and calibration.

INTRODUÇÃO: As Hemoglobinopatias podem ser divididas em Talassemias e Doença Falciforme (DF), mas do ponto de vista clínico, ambas apresentam um quadro de anemia hemolítica crônica, o que acarreta uma série de complicações, entre estas a Hipertensão Pulmonar (HP). Estima-se que cerca de 20-40% da população com DF/talassemia apresente HP, sendo que este diagnóstico está associado a uma elevada morbi-mortalidade. Poucos estudos avaliaram esta prevalência em crianças. O Objetivo deste estudo foi avaliar a prevalência desta complicação na população pediátrica, e associá-la com características clínicas e laboratoriais. MÉTODOS: Estudo de Corte Transversal, com avaliação de 45 pacientes com diagnóstico de DF ou Talassemia maior/ intermédia entre 3-18 anos, atendidos de forma consecutiva no ambulatório de Hemoglobinopatias do HCPA. Os pacientes foram submetidos a um ecocardiograma para estimativa da pressão sistólica da artéria pulmonar, sendo que foi considerado como tendo risco de HP os pacientes com velocidade de regurgitação tricúspide (VRT) ≥ 2,5m/s. Foram obtidos dados clínicos e laboratoriais para avaliação dos parâmetros hemolíticos, função hepática e renal por levantamento de prontuário e comparados os grupos. RESULTADOS: 15% (6/40) dos pacientes apresentaram VRT ≥ 2,5m/s, sugestivo de HP, sendo que destes pacientes todos tinham diagnóstico de Anemia Falciforme (AF). Considerando apenas esta população, a prevalência de HP aumenta para 20% (6/30). A população com VRT ≥ 2,5m/s apresentou média de idade mais elevada, Hb mais baixa, RDW mais alargado, reticulócitos e LDH mais elevado que o grupo com VRT < 2,5m/s. A principal intercorrência clínica nesta população foi a ocorrência de priapismo (p< 0,05). CONCLUSÕES: Os pacientes com Hemoglobinopatias estão em risco aumentado para desenvolvimento de HP desde a infância, principalmente aqueles com AF. Estes pacientes apresentam os parâmetros laboratoriais sugestivos de hemólise alterados, assim como outros sintomas associados ao quadro hemolítico como o priapismo quando comparados com pacientes com VRT normal. Desta forma sugere-se a realização de triagem com ecocardiograma nesta população de forma precoce. / INTRODUCTION: The Hemoglobinopathies can be divided in Thalassemias and Sickle Cell Disease (SCD), but clinically both present with chronic hemolytic anemia, which leads to various complications, one of them being Pulmonary Hypertension (PH). About 20-40% of patients with SCD have PH, and this diagnosis is associated with a high risk of mortality. The objective of this study was to estimate the prevalence of this complication in the pediatric population, and associate clinical and laboratory characteristics. METHODS: A cross sectional descriptive study, with the evaluation of 45 patients with diagnosis of SCD or thalassemia major/intermedia between 3-18 years, which received treatment at the Hemoglobinopathies ambulatory at HCPA. The patients were submitted to an echocardiogram to estimate the pulmonary artery systolic pressure, being considered to have PH patients with a tricuspid regurgitate jet velocity (TRV) ≥ 2.5m/s. Clinical and laboratory data were obtained to evaluate hemolytic parameters, renal and liver function and compared between groups. RESULTS: 15% (6/40) of patients had a TRV ≥ 2.5m/s, suggestive of PH, of which all had Sickle Cell Anemia (SCA). Considering this group of patients alone the prevalence would be of 20% (6/30). Patients with TRV ≥ 2.5m/s had a higher median age, lower hemoglobin count, higher RDW, reticulocyte and DHL then patients with a TRV < 2.5m/s. The major clinical feature was the occurrence of priapism (p<0,05). CONCLUSIONS: Patients with diagnosis of hemoglobinopathies are at higher risk of developing PH since early childhood, especially those with SCA. These patients showed a higher level of hemolytic parameters, as well as symptoms associated with hemolysis, like priapism, when compared with patients with a normal TRV. Therefore, it would be indicated to submit these patients to an echocardiogram routinely in their early years.

Orientadores: Fernando Ferreira Costa, Nicola Conran / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T10:27:56Z (GMT). No. of bitstreams: 1 Gambero_Sheley_M.pdf: 2005109 bytes, checksum: faec483bdfe41c20b920e16808d8eb59 (MD5) Previous issue date: 2006 / Resumo: A anemia falciforme é um distúrbio genético da hemoglobina causado por uma mutação de ponto produzindo hemoglobina S (HbS) que quando desoxigenada causa, entre outros sintomas, eventos vaso-oclusivos. Um dos mecanismos indicados como causador da vaso-oclusão é a adesão de hemácias falciformes ao endotélio dos vasos. Eritrócitos falciformes e normais aderem ao endotélio vascular utilizando moléculas de adesão como, CD 36 e integrina VLA-4, entre outras moléculas de adesão. Hidroxiuréia (HU) é um agente quimioterápico que diminui a freqüência de crises vaso-oclusivas, síndrome torácica aguda e necessidade de transfusão. Longos tratamentos com HU levam a uma redução global das proteínas de superficie dos neutrófilos, monócitos e linfócitos, além de aumentar os níveis de Hemoglobina fetal (Hb F), que inibe a polimerização da célula falciforme desoxigenada. O NO é um importante vaso-dilatador responsável por inúmeros efeitos benéficos durante as crises vaso-oclusivas. Estudos demonstram que o NO pode diminuir a expressão endotelial de moléculas de adesão, mas estudos diretos sobre os níveis de expressão dessas moléculas em anemia falciforme na presença de NO não tem sido encontrados na literatura. Deste modo objetivamos neste trabalho, analisar a expressão, gênica e protéica, e a função das moléculas de adesão VLA-4 (CD49d ou cadeia a. e CD29 ou cadeia 13) e CD 36 em células vermelhas de pacientes com anemia falciforme com e sem terapia com HU e os efeitos do tratamento in vitro com HU e agentes doadores de NO na adesão dessas células. Analisando a adesão das células vermelhas normais e de pacientes com e sem terapia com HU confirmamos que as células vermelhas de pacientes falciformes são mais aderentes que as células vermelhas normais e que a terapia com HU provoca uma diminuição dessa aderência. A citometria de fluxo comprovou a maior presença de células CD36+ e CD49d+ além de maior índice de expressão dessas moléculas nos pacientes falciformes em relação ao controle e a diminuição da expressão e positividade dessas moléculas em células de pacientes em terapia com HU quando comparadas com pacientes sem terapia. Adicionalmente, a análise por Real Time PCR demonstrou que a expressão gênica de CD36, CD49d e CD29 em reticulócitos falciformes é significativamente menor em pacientes em terapia com HU quando comparado com pacientes que não recebem essa terapia. Em resumo, nossos resultados sugerem que: as propriedades adesivas à fibronectina (FN) são aumentadas em células SS e que estas propriedades diminuem nos pacientes que tomam a terapia de HU; a terapia com HU diminui a expressão protéica e a positividade, das células vermelhas falciformes, hemácias e células jovens, para os receptores CD36 e CD49d; e a expressão gêniea das moléculas de adesão CD36 e CD49d em reticulócitos de pacientes com anemia falciforme que recebem terapia com HU é diminuída em relação ao grupo de pacientes falciformes que não recebem essa terapia / Abstract: Sickle cell vaso-occlusion constitutes a complex process involving interactions between SS red blood cells (RBC), endothelial cells, leukocytes, platelets, coagula tive factors and plasma proteins. Propagation ofthe vaso-occlusive process in sickle cell anemia (SCA) is a complex process involving the adhesion of SS red cells and reticulocytes to the vascular endothelium. The effect of hydroxyurea therapy (HUT) on the adhesive properties of sickle red cells and the expression of adhesion molecule genes by erythroid cells of SCA individuals is not yet fully understood. The expressions of the CD36 gene and the VLA-4 integrin subunit genes, CD49d (a-subunit) and CD29 (J3-subunit), were compared in the reticulocytes of steady-state SCA patients and patients on HUT using Real-Time PCR Basal adhesion of red cells ftom these subjects was also compared using static adhesion assays, as was surface protein expression, using flow cytometry. Basal sickle red cell adhesion to fibronectin was significantly greater than that of normal cells (P<O.OI); in contrast, HUT significantly decreased (P<O.OI) red cell adhesion to levels similar to those of control cells and this decrease could not be justified solely by alterations in reticulocyte numbers in this population. Accordingly, flow cytometry demonstrated that HUT significantly decreased CD36 and CD49d surface expression (P<O.Ol) and, importantly, significant reductions in the expressions of the CD36, CD49d and CD29 genes were seen (P<O.O5) in the reticulocytes of SCA patients on HU. Taken together, data support the hypothesis that HUT reduces the adhesive properties of sickle cells and that this decrease appears to be mediated, at least in part, by a decrease in the gene and, consequently, surface protein expression of adhesion molecules such as VLA-4 and CD36 / Mestrado / Patologia Clinica / Mestre em Ciências Médicas

Orientadores: Nicola Amanda Conran Zorzetto, Fernando Ferreira Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T12:14:33Z (GMT). No. of bitstreams: 1 Proenca-Ferreira_Renata_M.pdf: 950238 bytes, checksum: 21ee0800d218d95b35b72ea1eeaab7e3 (MD5) Previous issue date: 2009 / Resumo: Anemia falciforme (AF) é uma doença causada por uma mutação de ponto, que resulta na formação de hemoglobina S (HbS). A polimerização de HbS desoxigenada resulta na deformação, enrijecimento e fragilização das células vermelhas, anemia hemolítica e eventos vasos-oclusivos, principal causa de morbidade nos pacientes com AF. A adesão anormal das células brancas e vermelhas ao endotélio diminui o fluxo de sangue na circulação micro-vascular, principal fator envolvido na vaso-oclusão. O objetivo deste trabalho foi comparar as propriedades adesivas de plaquetas de indivíduos sadios (AA) com as plaquetas de pacientes com AF (SS) e em terapia com hidroxiuréia (HU), e quais moléculas de adesão e sinalização estão envolvidas nesta adesão. A adesão basal de plaquetas ao fibrinogênio (FB) do grupo de pacientes SS foi significativamente maior em relação às plaquetas AA, entretanto, as plaquetas de pacientes SSHU mostraram uma adesão similar às plaquetas AA. As plaquetas AA, SS e SSHU quando estimuladas com trombina (TB), apresentaram uma adesão significativamente maior em relação às suas adesões basais. Por outro lado, não houve diferenças significativas entre as adesões basais das plaquetas AA, SS e SSHU ao colágeno como ligante. A citometria de fluxo foi utilizada para comparar a expressão e ativação das principais moléculas de adesão nestas plaquetas, e identificou-se um aumento de expressão da integrina aIIbß3 na sua conformação de ativação, na superfície das plaquetas SS, em relação às plaquetas AA e SSHU. A molécula P-selectina (CD62P) foi encontrada com maior expressão também na superfície das plaquetas SS. Ensaios de adesão utilizando anticorpos específicos para as moléculas de adesão indicaram um possível papel para a integrina aIIbß3 na adesão de plaquetas ao FB. O AMPc é um importante inibidor de ativação plaquetária, e os níveis intraplaquetários de adenosina manofosfato cíclica (AMPc) das plaquetas SS foram significativamente menores em relação às plaquetas AA e SSHU. A co-incubação das plaquetas com TB reduziu significativamente os níveis de AMPc nas plaquetas AA, e SSHU, e nas plaquetas SS essa redução não foi significativa. Além disso, foi interessante notar que os níveis de hemoglobina fetal (HbF) em pacientes SS e SSHU apresentaram uma significativa correlação com os níveis de AMPc. Em relação aos níveis intraplaquetários de guanosina monofosfato cíclica (GMPc), importante inibidor de agregação plaquetária, das plaquetas AA, SS e SSHU não houve diferenças estatisticamente significativas, entretanto com estímulo de trombina houve um aumento significativo de GMPc nas plaquetas AA. A incubação das plaquetas com o cilostazol (inibidor específico da fosfodiesterase 3A, PDE3A) levou a uma redução da adesão de plaquetas SS, e sugere-se que as plaquetas SS possuem a atividade de fosforilação da PDE3A aumentada, e esteja relacionada com a degradação de AMPc nessas plaquetas. Além disso, dados indicam que as vias de sinalização dependentes de PKA, PKG e PKC não estão envolvidas na adesão alterada das plaquetas SS. A atividade funcional nos ensaios com agregação plaquetária de pacientes com AF está alterada, mas será necessário que novos experimentos sejam realizados para maiores conclusões. Os resultados sugerem que as plaquetas de pacientes AF circulam num estado ativado e que elas possuem maior capacidade de aderirem às proteínas que podem ser encontradas na matriz extracelular (MEC) e na superfície da parede vascular. Esta adesão aumentada está associada com os níveis diminuídos de AMPc intraplaquetários e ativação da integrina aIIbß3. Estas mesmas alterações parecem ser revertidas nos pacientes em uso de HU. Resultados sugerem que as plaquetas podem ter um papel importante no processo de vaso-oclusão. Quando estão ativadas, estas plaquetas servem como fonte importante para mediadores inflamatórios que, por sua vez, podem levar à exacerbação da inflamação e ativação celular no local. / Abstract: Sickle cell disease (SCD) is caused by a point mutation that results in the formation of Hemoglobin S (HbS). The polymerization of deoxygenated HbS causes deformation of red cells, which then adopt a sickle shape and become rigid and fragile. Hemolytic anemia and vaso-occlusive events are the main cause of morbidity in SCD; abnormal adhesion of white and red cells to the endothelium decreases the blood flow in the microcirculation and appears to be the main factor involved in vaso-occlusion. The objective of this study was to compare the adhesive properties of platelets from healthy individuals (AA platelets) with those of platelets from SCD patients (SS platelets) and from patients on HU therapy (SSHU platelets), as well as the adhesion molecules and signaling pathways that may be involved in this adhesion. The basal adhesion of SS platelets to fibrinogen (FB) was significantly higher than that of AA platelets; in contrast, SSHU platelets demonstrated a similar adhesion to that of AA platelets. Platelets from AA, SS and SSHU individuals, when stimulated with thrombin (TB), all presented significantly higher adhesions when compared with their basal adhesions. In contrast, there were no significant differences between the adhesions of AA, SS and SSHU platelets when collagen was used as a ligand. Flow cytometry was utilized to compare the expression and activation of the main adhesion molecules on AA, SS and SSHU platelets and identified a significantly higher expression of the ?IIb?3 integrin in its activated conformation on the surface of the SS platelets, in relation to the AA and SSHU. Expression of the P-selectin adhesion molecule (CD62P) was also found to be increased on the surface of SSHU platelets. Adhesion assays utilizing specific antibodies for the activated ?IIb?3 and P-selectin indicated a possible role for the ?IIb?3 integrin in the adhesion of platelets to FB. The cyclic nucleotide, cyclic adenosine monophosphate (cAMP) is an important inhibitor of platelet aggregation. Intraplatelet levels of cAMP were found to be significantly lower in SS platelets compared to AA and SSHU platelets. Co-incubation of platelets with TB significantly reduced levels of cAMP in the AA and SSHU platelets, but in SS platelets this decrease was not significant. Interestingly, levels of fetal hemoglobin (HbF) in SCD patients (both SS and SSHU) were found to correlate significantly with levels of platelet AMPc. With regard to intraplatelet levels of cyclic guanosine monophosphate (cGMP), there were no significant differences found between AA, SS and SSHU platelets, however following a TB stimulus AA platelets demonstrated a significant increase in intracellular cGMP. Phosphodiesterase 3A (PDE3A) is the main cyclic nucleotide hydrolyzing enzyme in platelets. Incubation of SS platelets, but not AA or SSHU platelets, with cilostazol (specific inhibitor of PDE3A) resulted in a significant reduction in their adhesion to FB, suggesting that PDE3A activity in SS platelets may be activated and that augmentation of cAMP is capable of reverting increased SS platelet adhesion. Additional experiments indicate that Protein kinase A (PKA), PKG and PKC dependent signaling pathways are not involved in the altered adhesion of SS platelets. The functional activity of SS platelets was found to be altered in platelet aggregation assays, however further experiments are required to draw conclusions from these data. Results of this study suggest that platelets from SCD individuals circulate in an activated state and that they present a greater ability to adhere to proteins that may be encountered on the vessel wall. This augmented adhesion is associated with decreased levels of intraplatelet cAMP and activation of the ?IIb?3 integrin. These alterations appear to be reversed in patients on HU therapy. Results suggest that platelets may have an important role in the vaso-occlusive process.When activated these cells are an important source of inflammatory mediators that may, in turn, result in an exacerbation of cellular activation at the vaso-occlusive site. / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The ulcers of the lower limbs are cited as the main cutaneous manifestation of sickle cell anemia, presenting a chronic course, with pain and many complications. Treatment of sickle ulcers is complex, involving care wound bed, management of anemia, pain management and treatment of opportunistic infections, among the various proposed treatments highlight the use of covers with inelastic bandage impregnated with zinc, the boot Unna. However there are still no controlled trials to prove the efficacy of treatment. Objective: Compare treatment with conventional dressing to the use of Unna boot in patients with sickle cell anemia and ulcers in the limbs. Methodology: This is a randomized clinical trial, which analyzed patients with sickle cell ulcers that took the Unna boot , comparing them with patients with sickle cell ulcers who used the conventional dressing . Treatments were performed in a period of six weeks. Statistically analyzed the areas of lesions in three periods: at baseline (D0) in the third week (D3) and the sixth week (D6). Results: Participated in this study 19 patients with a mean age of 35.9 years (95% CI 29.1 to 42.8), 53% (10/19) were male. In these individuals was analyzed the healing of ulcers in 40 lower limbs of people with sickle cell anemia 57% (23/40) in the experimental group and 43% (17/40) in the control group. There was a mean variation in lesion area when used Unna boot of 20.2 cm2 at T0 time, 17.9 cm2 in time T3 and 6.2 cm2 in time T6 (P < 0.001), mean percentage of total reduction of 77 1%, obtained by Tarajad index, when used as a simple dressing ranged from 31.3 cm2 35.8 cm2 33.9 cm2 at times T0, T3 and T6, respectively (P <0.001) and an average percentage of 22.8 %. Conclusion: The results suggest that the use compression therapy with Unna boot is an effective treatment of lower limb ulcers in patients with sickle cell anemia, aimed at reducing ulcer area, improvement of the injury aspect and pain alleviation. / As úlceras em membros inferiores são citadas como a principal manifestação cutânea da anemia falciforme, apresentando um curso crônico, com dor e muitas complicações. O tratamento das úlceras falcêmicas é complexo, envolvendo cuidados com o leito da lesão, manejo da anemia, controle da dor e tratamento de infecções oportunistas, dentre os diversos tratamentos propostos destaca-se o uso de coberturas com bandagem inelástica impregnada com zinco, a bota de Unna. No entanto ainda não existem ensaios clínicos que comprovem a eficácia do tratamento. Objetivo: Comparar o tratamento com curativo convencional à utilização de bota de Unna em pacientes com anemia falciforme e úlceras em membros inferiores. Método: Trata-se de um ensaio clínico randomizado, onde foram analisados pacientes com úlcera falcêmica que fizeram uso da bota de Unna, comparando-os com pacientes com úlceras falcêmicas que fizeram uso do curativo convencional. Os tratamentos foram realizados em um período de seis semanas. Foram analisadas estatisticamente as áreas das lesões em três períodos: no momento inicial (D0), na terceira semana (D3) e na sexta semana (D6). Resultados: Participaram dessa pesquisa 19 pacientes com idade média de 35,9 anos (IC95% = 29,1 a 42,8), sendo 53% (10/19) do sexo masculino. Nesses indivíduos foi analisada a cicatrização de 40 úlceras em membros inferiores de pessoas com diagnóstico de anemia falciforme sendo 57% (23/40) no grupo experimental e 43% (17/40) no grupo controle. Houve uma variação média da área lesional quando utilizado bota de Unna de 20,2 cm2 no tempo T0, 17,9 cm2 no tempo T3 e 6,2 cm2 no tempo T6 (P<0,001), com média percentual de redução total de 77,1%, obtido através do índice de Tarajad, enquanto quando se usou o curativo simples teve uma variação de 31,3 cm2, 35,8 cm2, 33,9 cm2, nos tempos T0, T3 e T6 respectivamente (P<0,001), e um percentual médio de 22,8%. Conclusão Os resultados sugerem que a utilização da terapia compressiva com bota de Unna constitui um tratamento efetivo das úlceras de membros inferiores em pacientes portadores de anemia falciforme, atuando na redução da área da úlcera e na melhora do aspecto lesional.

La drépanocytose, pathologie génétique de l'hémoglobine la plus fréquente en France, se caractérise par des crises douloureuses paroxystiques, dont la survenue apparaît souvent depuis la plus jeune enfance. La majorité des individus rencontrés en métropole française sont issus de la migration, provenant de départements d'Outre-Mer et de pays d'Afrique Sub-Saharienne.Par une méthodologie qualitative, nous observons les répercussions des crises douloureuses pathognomoniques de la drépanocytose, que nous considérons comme traumatogènes, sur la dynamique identitaire de sujets adultes. D'une part, nous suggérons que ces crises se figurent tel un évènement déstructurant, menaçant l'équilibre identitaire du sujet, de par l'imprévisibilité de leur survenue et leur risque létal. D'autre part, au vu de cette potentialité traumatique, nous les envisageons comme structurant la dynamique psychique du sujet, au travers des modalités singulières que ce dernier entretient avec son corps. La confrontation au Réel de la Mort, le vécu d’effroi, la menace d’annihilation psychique causée par la douleur, ainsi que leur répétitivité et le sentiment d’incertitude quant à leur soulagement, inscrivant parfois le sujet dans un temps dissociatif long, dévoilent un risque de développer un syndrome psychotraumatique. Pour autant, de par leur récurrence, elles engendrent une relation au corps où le sujet anticipe le surgissement de la douleur, laquelle apparaît tel un repère sensoriel, même latent, auquel il se fie pour se mouvoir dans son environnement.Dans cette visée exploratoire, nous appréhendons le sentiment et la construction identitaire des sujets, notamment au regard des étiologies plurielles affiliées à la drépanocytose, relatives aux savoirs profanes de la culture d’origine et aux savoirs médicaux disponibles. Ces diverses explications causales génèrent des représentations et des désignations socio-culturelles du sujet drépanocytaire, particulièrement dans le pays d’origine. Le processus identitaire semble malmené par les contraintes liées à la maladie, contribuant au sentiment d’être différent des autres, lequel est également alimenté par ces spécificités socio-culturelles. Au-delà des bouleversements identitaires liés à la migration, l’analyse met en exergue les réactions et les ressources employées face à la maladie, et illustre les mouvements de distanciation des sujets face à une identité parfois vécue comme « subie ».En outre, nous avons recueilli des données quantitatives concernant l’observance thérapeutique, les niveaux d’anxiété, de fatigue, de catastrophisme, ainsi que les croyances et les perceptions associées à la douleur. En moyenne, les sujets déclaraient être observants quant à leur traitement. Les niveaux moyens d’anxiété et de catastrophisme se sont avérés modérés. La fatigabilité s’orienterait sur une dimension sensorielle et affective plutôt que comportementale et cognitive. Concernant leur douleur, les sujets avaient tendance à l’appréhender comme mystérieuse et pérenne, ne se percevaient que peu coupables quant à sa présence et semblaient hésitants sur son caractère intermittent ou continu.Le premier axe d’étude de l’hypnose et de la pratique de l’autohypnose s’attachait à les estimer en tant que facteurs d’atténuation des symptômes mesurés par le biais des échelles d’évaluation. Le deuxième intéressait la nécessaire dimension intersubjective de l’hypnose. Aucune différence significative n’a été retrouvée entre les deux temps de mesures qui suggérerait une efficacité symptomatique de l’hypnose. Au travers du discours des sujets, l’influence de l’hypnose résiderait dans la (ré)appropriation du vécu du corps et de l’histoire subjective grâce à l’investissement relationnel sécurisant au praticien. Enfin, la pratique de l’autohypnose se révélerait efficace en tant que réactualisation de cette relation, mobilisant le sujet dans un engagement à lui-même. / Sickle-cell disease, the most common genetic pathology of haemoglobin in France, is characterized by painful paroxysmal pain attacks, often occurring since early childhood. The majority of the individuals met in the French metropolis are migrants, coming from overseas departments and countries in Sub-Saharan Africa.Using a qualitative methodology, we observe the repercussions of painful pathnomonic crisis in sickle-cell disease, which we consider traumatogenic, on the identity dynamic of adult subjects. On one hand, we suggest that these crises appear as a destructuring event, threatening the subject's identity balance, due to the unpredictability of their occurrence and their lethal risk. On the other hand, in view of this traumatic potentiality, we consider them as structuring the psychic dynamics of the subject, through the peculiar modalities that he maintains with his body. The confrontation with the Reality of Death, the experience of dread, the threat of psychological annihilation caused by pain, as well as their repetitiveness and the feeling of uncertainty as to their relief, sometimes placing the subject in a long dissociative time, reveal a risk of developing psychotraumatic syndrome. However, because of their recurrence, they generate a body relationship where the subject anticipates the onset of pain, which appears as a sensory reference point, even latent, which he relies on to live in his environment.In this exploratory aim, we apprehend the feeling and identity construction of subjects, particularly in regard of the plural etiologies affiliated with sickle-cell disease, related to the secular knowledge of the culture of origin and the medical knowledge available. These various causal explanations generate socio-cultural representations and designations of the sickle cell disease subject, particularly in the country of origin. The identity process seems to be mishandled by disease related constraints, contributing to the feeling of being different from others, which is also fuelled by these socio-cultural specificities. Beyond the identity changes linked to migration, the analysis highlights the reactions and resources used in dealing with illness, and illustrates the movement of subjective distanciation subjects from an identity that is sometimes experienced as "undergone".In addition, we collected quantitative data on adherence, anxiety, fatigue, catastrophizing, and beliefs and perceptions associated with pain. On average, subjects reported being observant about their treatment. Average levels of anxiety and catastrophizing were moderate. Tiredness would tend to a sensory and emotional dimension rather than a behavioural and cognitive one. Regarding their pain, subjects tended to perceive it as mysterious and lasting, don’t feel guilty about its presence and seemed hesitant about its intermittent or continuous nature.The first axis of study of hypnosis and the practice of self-hypnosis focused on estimating them as mitigating factors for symptoms measured through assessment scales. The second concerned the necessary inter-subjective dimension of hypnosis. No significant differences were found between the two measurement times that would suggest symptomatic efficacy of hypnosis. Through the subjects' words, the influence of hypnosis could be seen in the (re)appropriation of the body's experience and subjective history thanks to the practitioner's secure relational investment. Finally, the practice of self-hypnosis would prove to be effective as an update of this relationship, mobilizing the subject in a commitment to himself.

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PURPOSE: Sickle cell disease (SCD) is an inherited blood disorder that affects the hemoglobin protein of red blood cells and has a significant impact on morbidity, mortality, and quality of life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD. However, hydroxyurea has not been optimally utilized for those with SCD. The purpose of this study was to evaluate reasons for hydroxyurea use, from the perspectives of providers, adults with SCD, and parents/caregivers of children with SCD, as well as perceived barriers to its use. We examined indications and reasons for being “on hydroxyurea,” defined by patients as currently taking hydroxyurea, and reported on pain frequency, perceptions of barriers, hydroxyurea adherence, and health care access for patients with SCD who were either on and not on hydroxyurea. METHODS: We conducted a cross sectional analysis of data collected within the Pacific Sickle Cell Regional Collaborative (PSCRC), a consortium of nine western U.S. states. Individuals were eligible for this study if they 1) had a confirmed diagnosis of SCD, 2) were followed at one of the PSCRC sites, and 3) were eligible for hydroxyurea therapy. Parents/caregivers of children with SCD less than 18 years and adults with SCD 18 years and older completed a brief survey about hydroxyurea use, indications, side effects, pain frequency, number of hospital and emergency department (ED) admissions per year, and individual and family perceptions of barriers to hydroxyurea use. Participants completed a follow-up survey annually, but we reported only on baseline data. Data collection occurred between February 2016 and May 2018. RESULTS: Individuals with SCD (n = 413) included 1) children (n=178; 6.7 ± 3.4 years), 2) adolescents (n=66; 15.0 ± 1.4 years), 3) young adults (n=57; 21.4 ± 2.6 years), and 4) adults (n=112; 39.2 ± 10.6 years). The majority were predominantly female (51.6%), African American (93.2%), and had HgbSS (74.1%) genotype. The majority of children (65.2%), adolescents (62.1%), and young adults (54.4%) were on hydroxyurea; fewer adults (39.3%) were on hydroxyurea. The majority with HgbSS (65.5%) were adherent to hydroxyurea. There was no significant difference in hospitalizations for pain, ED visits, and pain severity in the previous 12 months between individuals who were and were not on hydroxyurea, and between individuals who were and were not adherent to hydroxyurea. For those with a current prescription for hydroxyurea, the majority (66.5%) were receiving hydroxyurea for recurrent pain episodes or acute chest syndrome (19.9%). Hydroxyurea was discontinued because of patient/family preference (34.5%), chronic transfusions (31.1%), and side effects (24.1%). Patients prescribed hydroxyurea for empiric use (n=21) had fewer hospitalizations for pain, ED visits, and severe pain interfering with daily activities. The major barriers to hydroxyurea use, from the perspective of individuals with SCD or their caregivers, were 1) forgetting to take the medicine (19.4%), 2) worried about side effects (16.4%), and 3) lack of knowledge about hydroxyurea (13.6%). Fewer young adults (49.1%) and adults (50.0%) had primary care providers than children (78.1%) and adolescents (65.2%). CONCLUSIONS: Barriers to hydroxyurea use persist with emerging solutions to alleviate these barriers. For this sample, while hydroxyurea prescription rates by sickle cell specialists were similar to what has been seen in some other studies, neither hydroxyurea use nor adherence were associated with decreased frequency of hospitalizations for pain, ED visits, and severe acute pain episodes in the previous 12 months. Future studies need to evaluate hydroxyurea prescription patterns, duration on hydroxyurea, and adherence to hydroxyurea. Healthcare providers are recommended to prescribe hydroxyurea for eligible individuals who may benefit from it, such as those HgbSS or HgbS-β0 thalassemia genotype, and prescribe for empiric use to minimize complications. Provider and patient education about hydroxyurea could reduce common barriers experienced by individuals with SCD. It is important to customize educational resources to specific concerns for different age groups. Individuals 18 years and older with SCD have been documented with more ED visits and hospitalizations due to pain, most likely because they did not have a primary care provider and an adult hematologist with expertise in SCD. Future studies need to evaluate whether primary care providers who receive SCD education may promote hydroxyurea use and adherence. Dedicating time and resources for shared decision making between providers and patients/families can address concerns about hydroxyurea and increase patient/family confidence when deciding about hydroxyurea. As more disease-modifying therapies become available for individuals with SCD, strategies for shared decision making facilitate standardization and optimize the use of hydroxyurea and emerging therapies.

La drépanocytose ou anémie falciforme est la maladie génétique la plus répandue dans le monde. Elle affecte plus particulièrement les populations des régions africaines sub-sahariennes, du sous-continent Indien et celles issues de ces populations. La Guadeloupe, archipel des Antilles françaises est une zone à forte prévalence drépanocytaire. La drépanocytose se caractérise par des anomalies de l’hémoglobine et du globule rouge qui mènent à des complications aigues et chroniques pouvant toucher tous les organes, dont les yeux. Récemment, plusieurs auteurs ont rapporté une prévalence importante de la maculopathie dans la drépanocytose mais la physiopathologie reste très mal comprise. Ainsi, nous avons réalisé deux études. La première, consistait à étudier la prévalence de la rétinopathie et de la maculopathie drépanocytaires et de tester l’association entre ces deux complications. De plus, nous avons recherché un éventuel lien avec différentes anomalies biologiques. Nous avons montré que la rétinopathie et la maculopathie étaient deux complications fréquentes mais indépendantes dans la drépanocytose. Les résultats de cette première étude ne supportent pas un lien éventuel entre les anomalies hématologiques, hémorhéocarlogiques ou le génotype et ces deux complications. Dans une deuxième étude nous avons essayé de mieux caractériser la maculopathie drépanocytaire en réalisant un électrorétinogramme multifocal (mfERG) et une tomographie en cohérence optique spectral domain (SD-OCT) chez des patients SS et SC sans signe clinique de maculopathie. Nous avons pu mettre en évidence des altérations maculaires électrophysiologiques chez les patients drépanocytaires paraissant exempt de toute maculopathie à l’examen clinique. Par ailleurs, nous avons retrouvé que la maculopathie drépanocytaire est aussi fréquente chez les SS que chez les SC.Notre travail confirme le caractère fréquent des complications rétiniennes drépanocytaires. Cependant, elles apparaissent comme complètement indépendantes l’une de l’autre et les mécanismes physiopathologiques sous-jacents restent mal compris / Sickle cell disease (SCD) also known as sickle cell anemia is the most common genetic affection in the world. Most of SCD cases occur in sub-Saharan Africa, india and among people of African and indian descent living in other parts of the world. SCD is common in Guadeloupe, French West indies. It results in an abnormal hemoglobin leading to rigid sickle like shape red blood cells responsible for a great number of acute and chronical systemic complications including ophthalmic affections. Recently, a wild prevalence of maculopathy has been reported by several authors but its pathophysiology remains unclear.We performed two studies. The aim of the first one was to investigate the prevalence of SCD retinopathy and maculopathy and to test the association between these two conditions. Moreover, we looked for a possible link with biological abnormalities. Our study confirmed that SCD maculopathy and retinopathy are common but they remain two independent affections. Nevertheless, we found no association with hematological parameters, blood rheology of genetic.In the second study, we described and compared spectral domain ocular coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) findings in patients with SCD without clinical sign of maculopathy, according to the hemoglobin genotype. We found electrophysiological macular dysfunction in SCD patients with no clinical maculopathy. Furthermore, maculopathy was as frequent in SCA than in SCC patients.Our work confirms that retinal affections are common in SCD. Nevertheless, retinopathy and maculopathy seem to be two independent complications and their pathophysiology remains misunderstood.