No description available.

Die vorliegende Arbeit quantifiziert die Korrelationen zwischen blutrheologischen Parametern und Erythrozyten-Indizes an einem repräsentativen und gut definierten Kollektiv gesunder Frauen im Vorfeld eines elektiven gynäkologischen Eingriffes. Gemäß der erhobenen Resultate besteht bei 286 gesunden Frauen mittleren Alters zwischen der Verformbarkeit, dem MCV und dem MCH der Erythrozyten eine statistisch signifikante Korrelation, die in Gegenwart hoher Scherkräfte an Ausprägung zunimmt. Gleichzeitig vermindert sich mit zunehmender MCHC die Erythrozytenverformbarkeit stetig und statistisch signifikant, wobei dieser Effekt am deutlichsten in Gegenwart hoher Scherkräfte, wie diese beispielsweise in den Kapillaren der Endstrombahn anzunehmen sind, nachweisbar ist. / The physiological association between blood rheological parameters and red blood cell indices was investigated in otherwise healthy unselected women prior to elective gynaecological surgery. In a total of 286 healthy women was the RBCdeformability statically significantly positive correlated with MCV and MCH but statically significantly inversely correlated with MCHC. The correlation between RBC Indices and RBC deformability was most remarkable during moderate shear force exposure.

No description available.

Background: Red cell transfusions can lead to alloimmunization; however, pediatric alloimmunization frequency has not been well studied, and it may vary among diagnostic subgroups. Subgroups such as pediatric hematology/oncology patients require numerous transfusions during chemotherapy, but the immunosuppressive effect of chemotherapy on alloimmunization is unknown. One study demonstrated reduction in IgM and IgG in pediatric leukemia patients (Martín Ibáñez 2003); hence, one could hypothesize that chemotherapy suppresses alloimmunization. Objectives: This study aimed to: 1) describe alloimmunization frequency and antibody specificities in transfused pediatric patients; and 2) determine if chemotherapy affects the frequency of alloimmunization. Methods: A retrospective cohort study of pediatric patients (transfused between April 2002 and November 2011 at Hamilton Health Sciences) was performed. Data were extracted from 3 sources: a blood utilization database; the Laboratory Information System; and chart reviews. The chemotherapy treatment group included pediatric hematology/oncology patients stratified by HSCT status and diagnosis; control cohort included other pediatric patients not diagnosed with cancer. Control patients with hemoglobinopathies were analyzed separately due to increased alloimmunization. Alloimmunization was defined as clinically significant IgG alloantibody formation. Results: There were 1273 patients in the study: 949 in control group; 324 in study group. Alloimmunization was 1.6% overall: 0.6% (95% CI: 0, 1.47) in study group; 1.3% (95% CI: 0.58, 2.06) in control group. The association between chemotherapy and alloimmunization was not significant (p value = 0.38 Fisher’s exact test; OR 0.46, 95% CI: 0.10, 2.09). Due to low outcome rate, logistic regression to explore the association was not feasible. Conclusions: This is the first study exploring the frequency of alloimmunization in pediatric patients by diagnosis and the association between chemotherapy and alloimmunization. The frequency of alloimmunization was low and no association between chemotherapy and alloimmunization was observed. Low event rate would have contributed to low power. / Thesis / Master of Science (MSc)

No description available.

Sickle cell disease (SCD) is one of the most common genetic diseases worldwide. HbS polymerisation causes altered red blood cell (RBC) rheology and fragility, increase in blood viscosity with blockage of small blood vessels, and RBC membrane permeability changes. Excessive levels of cell-free Hb, high autoxidation of Hb, contribute to the production of reactive oxygen species (ROS) in SCD patients. In this work, oxidants showed direct and indirect effects on the main cation permeability pathways involved in dehydration of HbS/S RBCs - Psickle, the Gardos channel and the KCl cotransporter (KCC) - and thus on RBC volume causing polymersation. Psickle and Gardos channel activities showed significant correlation, consistent with the hypothesis that Ca2+ entry via Psickle causes activation of the Ca2+-dependent K+ channel. Treatment of SCD remains inadequate relying on the blood transfusion and supportive therapy depending on the organ affected. In the present study antioxidants and aromatic aldehydes showed some promising results towards future alternative treatments for SCD. Antioxidants showed inhibitory effects on the cation permeability pathways leading to inhibition of polymerisation and haemolysis and thus maintained RBC volume. Aromatic aldehydes interact with HbS and are usually given to increase oxygen affinity, thereby reducing its tendency to polymerise. GBT1118 had a marked inhibitory effect on all three cation permeability pathways. It reduced sickling, Psickle and Gardos activity. It inhibited KCC by affecting the regulatory protein phosphorylation cascade. It maintained RBC hydration, and stabilised RBCs. Historically Oman was the principal trading port of the Persian Gulf region, resulting in the complex mix of social and ethnic backgrounds. In 1989 a second mutation in the β chain of Hb, at position β121 was found in an Omani patient in addition to the usual HbS mutation at the β6 position, and termed HbS-Oman. At low percentage of HbS-Oman patients show severe SCD symptoms. Despite RBCs containing at most 25% HbS-Oman, there was high sickling percentage and K+ permeability showed many features similar to those seen in homozygous HbS/S patients. The presence of α thalassaemia was protective and represents an obvious potential prognostic marker for this rare SCD genotype. Overall, the present work contributes to elucidation of the pathogenesis of SCD, suggests approaches to the development of novel therapies and increases our understanding of a rare SCD genotype, HbS-Oman.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

No description available.

A deformabilidade é a característica que permite ao eritrócito normal de 7 a 8 micrômetros (m) circular por capilares de até 3m de diâmetro. Esse fenômeno depende da geometria celular, da viscosidade interna e das propriedades visco-elásticas da membrana eritrocitária. Dentre as várias técnicas de estudo da deformabilidade eritrocitária (DE), como: a aspiração por micropipeta, a filtração e a reoscopia, destaca-se a ectacitometria. Essa técnica utiliza um viscosímetro de fluxo laminar onde as modificações de forma dos eritrócitos são monitoradas continuamente por um feixe de raio LASER, processadas por microcomputador e inseridas em gráfico para posterior análise. A ectacitometria fornece o Índice de Deformabilidade (ID), o qual proporciona a medida da eliptocitogênese dos eritrócitos quando submetidos a uma força denominada shear stress. A anemia ferropriva é uma patologia muito freqüente na prática médica. Apresenta anormalidades morfológicas expressivas como: microcitose, hipocromia, ovalócitos, eliptócitos e hemácias em alvo. Alterações de deformabilidade eritrocitária foram descritas em diversas situações como na esferocitose hereditária, eliptocitose hereditária e anemias hemolíticas auto-imune. Na anemia ferropriva os trabalhos de deformabilidade eritrocitária são controversos. O presente estudo avalia a DE, utilizando a técnica da ectacitometria, em 21 pacientes portadores de anemia ferropriva documentada, antes e depois do tratamento com sais de ferro. Embora o tratamento da anemia tenha sido eficaz (Hb antes- 8,52 g/dl e Hb depois -12,74 g/dl), alguns pacientes persistiram com morfologia eritrocitária alterada. Os resultados demonstram DE diminuída em pacientes portadores de anemia ferropriva, quando comparada ao grupo controle (p< 0,0007). A ausência de normalização e manutenção da diferença estatística após a terapêutica (p< 0,03), em baixos valores de shear stress, pode ser atribuida à manutenção das alterações morfológicas eritrocitárias. Não foi verificada correlação entre o grau da anemia e a redução da DE. A diminuição da DE apresenta maior correlação com a microcitose, sendo que a hipocromia parece não interferir de maneira importante. A concomitância dos dois fatores pode somar ou anular os seus efeitos sobre a DE. O presente estudo sugere que o fator responsável pela diminuição da DE na anemia ferropriva é a microcitose. Recentemente, relatos de anemia ferropriva associada a fenômenos trombóticos aumentaram o interesse no estudo da DE para melhor compreensão desses casos. / The deformability allows the 7 to 8 cm red cell to circulate through capillaries of 3 cm. This phenomenon depends on cellular geometry, internal viscosity and viscoelastic properties of the membrane. Among the various techniques of erytrocyte deformability (ED) analysis such as: micropipette aspiration, filtration and reoscopy, we chose ektacytometry. This technique uses a laminar flow viscometry, where red cell shape changes are continuously monitorated by LASER, processed by a computer and inserted in a graphic for further analysis. Ektacytometry measures the Deformability Index (DI), which shows the size of eliptocytogenesis of the eritrocyte under shear stress force. Iron deficiency anemia is a very frequent disease in medical practice. It presents expressive morphologic alterations such as microcytosis, hypocromy, ovalocytosis, eliptocytosis and target cells. Erytrocyte deformability has been described in a number of situations like hereditary spherocytosis, hereditary elitptocytosis and autoimmune hemolytic anemia. Concerning iron deficiency anemia, authors are controversial. The present study evaluates erytrocyte deformability, using ectacytometry in 21 patients carrying documented iron deficiency before and after therapeutics with iron components. Although the anemia treatment proved to be efficient (before Hb- 8,52 g/dl and after Hb- 12,74 g/dl), some patients persisted with erytrocyte alteration morfology. Results demonstrate diminished erytrocyte deformability in people with iron deficiency anemia, when compared with the control group (p< 0,0007). The absence of regularization and maintenance of statistical difference after treatment (p< 0,03) in low shear stress can be attributed to the persistence of red cell anomalies. There is no relation between the level of anemia and reduced ED. The erytrocyte deformability diminished is greatly related to microcitosys, even if hipocromy seems to not interefere importantly. The two factors altogether can either sum or nulify the effects over erytrocyte deformability. The present study suggests that the responsible factor for diminished erytrocyte deformability is microcitosys. Recently, iron deficiency anemia has been associated to thrombotic phenomenon has raised interest in the studying of erytrocyte deformability, in order to understand such cases.

O grau de hemólise (GH) é um dos parâmetros de qualidade de concentrados de hemácias (CH). Conforme a Portaria 158/2016, ao menos 1% da produção mensal de CH deve ser controlada para o GH e 75% desta parcela deve apresentar resultado inferior a 0,8% de hemólise em relação à massa eritrocitária no último dia de validade do CH. O GH é definido como a porcentagem de hemoglobina livre (HbL) em relação à hemoglobina total (HbT) com a devida correção do volume globular do CH. O método analítico utilizado para a dosagem da HbL pela maioria dos hemocentros da rede pública nacional não referencia a fonte bibliográfica consultada. A hemoglobina liberada dos eritrócitos devido à hemólise é tóxica e desencadeia reações fisiopatológicas, resultando em implicações clínicas com gravidade que varia em função do grau de hemólise e do volume de hemácias transfundidas. O objetivo deste estudo foi avaliar os resultados de três metodologias analíticas espectrofotométricas para a determinação da HbL. Foram comparados o método de espectrofotometria direta de Harboe, o método de espectrofotometria direta de Cinco comprimentos de onda (5CO) e o método espectrofotométrico de Primeira derivada (1ªD). Os métodos de Harboe e de 5CO utilizam fórmulas matemáticas que convertem diretamente as absorbâncias lidas no espectrofotômetro UV/Visível em concentração de HbL. O método de 1ªD requer espectrofotômetro de varredura para a visualização dos espectros e a concentração da HbL é dada pelo valor referente à distância entre o vale e o pico de absorção da hemoglobina e do fator de correção, resultante de curva de calibração. Nesse estudo foram testados os sobrenadantes de 187 CH com CPDA-1 e CH com solução aditiva de SAG-Manitol. As amostras foram diluídas segundo o aspecto visual de hemólise do sobrenadante. A cada corrida analítica foram incluídas amostras controle preparadas in-house a partir de CH com concentração de HbT conhecida. O método de Harboe emprega leituras espectrofotométricas em 380, 415 e 450 nm. Para o método de 5 CO as absorbâncias são lidas em 370, 415, 510, 577 e 600 nm. O método da 1ªD utiliza o espectro de absorção analisado em 568 nm e 580 nm. A correlação entre as três metodologias testadas foi considerada ótima, evidenciando a equivalência entre os métodos. O método de Harboe mostrou-se compatível para a dosagem de baixas e de altas concentrações de HbL. O intervalo de linearidade espectrofotométrica oscilou de 0,00041 a 0,06075 g/dL. Entretanto, para resultados confiáveis de HbL, é imprescindível que o espectrofotômetro tenha especificação de largura da banda espectral igual ou inferior a 5 nm. O método de Harboe é embasado cientificamente, de fácil execução e baixo custo. Este método proporciona resultados fidedignos, reprodutíveis e padronizados, além de dispensar o uso de substâncias químicas perigosas. Complementarmente, disponibilizou-se um Procedimento Operacional Padrão para a determinação da HbL pelo método de Harboe e um Guia visual de hemólise para assessorar os profissionais que atuam na área de controle de qualidade de hemocomponentes em hemocentros nacionais. / The hemolysis is one of the parameters of the red cell concentrate (RCC) control quality. According to the Brazilian Ordinance 158/2016, at least 1% of the monthly production of RCC should be controlled regarding hemolysis and 75% of this amount should present below than 0.8% of hemolysis in relation to the red cell mass at end of RCC storage. The hemolysis is defined as the percentage of free hemoglobin (FHb), relative to the total hemoglobin (THb), with the appropriate correction of the RCC hematocrit. The analytical method used by most the national public healthcare blood centers to dosage FHb does not reference the bibliography that has been consulted. Hemoglobin released from the erythrocytes due to hemolysis is toxic and triggers pathophysiological reactions, resulting in clinical implications whose severity varies depending on the hemolysis grade and the amount of transfused RCC. The aim of this study was to evaluate the results of three spectrophotometric analytical methodologies for the determination of FHb. The Harboe spectrophotometry method, the method of five wavelengths direct spectrophotometry (5Wa) and the first derivative spectrophotometric method (1stD) were compared to each other. The Harboe and the 5Wa methods use mathematical formulas that directly convert the absorbance read from the UV/visible spectrophotometer in FHb concentration. The 1stD method requires scanning spectrophotometer to visualize the spectra and concentration of the FHb is given by the value calculated from the distance between the valley and the peak absorption of hemoglobin and a correction factor, resulting from the calibration curve. One hundred eighty-seven (187) RCC supernatants with CPDA-1 and RCC with SAG-mannitol additive solution were tested in this study. The samples were diluted according to the visual appearance of supernatants hemolysis. For each analytical run in-house control samples, prepared from RCC with known THb concentration, were included. The Harboe method employs spectrophotometric readings at 380, 415 and 450 nm. Absorbance is read at 370, 415, 510, 577 and 600 nm with the 5 Wa method. In the 1stD method the absorption spectrum is analyzed at 568 and 580 nm. There was correlation between the three tested methodologies that were tested, demonstrating equivalence between the methods. The Harboe method was compatible for dosage of low and high FHb concentrations. The spectrophotometer linear range varied from 0.00041 to 0.06075 g/dL. However, in order to achieve reliable FHb dosages it is imperative that the spectrophotometer has a spectral bandwidth equal to 5 nm or below. The Harboe method is scientifically based, easy to perform and inexpensive. It provides reliable, reproducible and standardized results, dismissing the use of dangerous chemical substances. In addition, this study has provided an Operational Procedure to determine FHb by the Harboe method and a Visual Guide of hemolysis to assist professionals working in the quality control of blood products.