Resumo em Inglês:

ABSTRACT Background: The large diversity of red blood cell antigens favors, especially in multi-transfused patients, the occurrence of autoimmunization and alloimmunization with the risk of hemolytic transfusion reactions. Thus, this study aimed to determine the rates of alloimmunization and autoimmunization in these individuals, as well as the types of alloantibodies and their systems, clinical and epidemiological aspects and the frequency of autoimmunity in alloimmunized and non-alloimmunized patients. Methods: In a retrospective study, 153 multi-transfused patients from 2006 to 2014 were evaluated. Sixty-eight had onco-hematological diseases, 64 had hemoglobinopathies and 21 had chronic renal failure. Descriptive analyses were carried out with the proportions being compared using the chi-square test, with the significance level set at 5%. Results: The Rh system was the most frequently involved (53.11%) and anti-E and anti-K (Kell system) were the most prevalent alloantibodies (21.87% each). Autoantibodies were found in ten patients (6.54%) with the percentages of autoimmunization in alloimmunized and non-alloimmunized individuals being 29.16% and 2.32%, respectively (p = 0.0001). There was a significant difference between autoimmunization and the number of transfusions (16.21% in 6–10 vs. 5.26% <6 vs. 2.56% >10; p = 0.0203) and diseases (19.04% in chronic renal failure vs. 6.25% in hemoglobinopathies vs. 2.94% in onco-hematological diseases; p = 0.0329). Conclusion: The results show a strong correlation between alloimmunization and autoimmunization. Moreover, they reinforce the need for further studies on the clinical and epidemiological profile of multi-transfused patients in relation to alloimmunity and autoimmunity, especially the latter, for a better understanding of its etiopathogenesis and physiopathogenesis.

Resumo em Inglês:

ABSTRACT Background: This study investigated the influence of two conditioning regimens on the chimerical status of 104 patients with acquired severe aplastic anemia. Methods: Patients were monitored for at least 18 months after related bone marrow transplantation and reaching partial or complete hematologic recovery. Group I patients (n = 55) received 200 mg/kg cyclophosphamide alone and Group II (n = 49) received 120 mg/kg cyclophosphamide associated with 12 mg/kg busulfan. Patients were classified in three chimerism levels according to the percentage of donor cells in the peripheral blood. Results: Chimerism ≤50% occurred in 36.4% of Group I and none of Group II; chimerism 51–90% was found in 20.0% of Group I and 10.2% of Group II; and chimerism >90% was found in 43.6% of Group I versus 89.8% of Group II. A significant association (p-value < 0.001) was found between conditioning type and chimerism levels. A higher number of infused cells was associated with higher levels of chimerism only in Group I (p-value = 0.013). Multivariate analysis showed that chimerism >90% is associated with the cyclophosphamide plus busulfan conditioning (p-value < 0.001) and higher number of infused cells (p-value = 0.009), suggesting that these factors are predictive of graft outcome. Regarding hematological recovery, higher chimerism levels were associated with higher neutrophil (p-value = 0.003) and platelet counts (p-value < 0.001) in Group I only. These results show that myeloablative conditioning favors full donor chimerism and non-myeloablative conditioning predisposes to mixed chimerism or autologous recovery of hematopoiesis. Conclusion: These data show that autologous recovery depends on the intensity of immunosuppression and that the immunosuppressive function of cyclophosphamide alone can induce this type of hematopoietic recovery.

Resumo em Inglês:

ABSTRACT Background: Cytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms. Methods: This study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters. Results: The proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients. Conclusions: Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.

Resumo em Inglês:

ABSTRACT Background: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. Methods: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. Results: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). Conclusions: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Resumo em Inglês:

ABSTRACT Background: Hematopoietic stem cell transplantation is a curative treatment for many patients with hematological disorders. Donor–recipient genetic disparity, especially involving the human leukocyte antigen system is a critical factor for transplant outcome. Objective: To evaluate retrospectively donor characteristics and correlations with the occurrence of acute and chronic graft-versus-host disease, disease-free survival and overall survival in a Brazilian population submitted to allogeneic hematopoietic stem cell transplantation between 1994 and 2012 in a single center. Results: Three hundred and forty-seven consecutive transplantations were included. Related transplants (81.2%) were significantly more common than unrelated transplants (18.7%); donor and recipient median ages were 34 (range: 1–61) and 33 (range: 3–65) years respectively with donor HLAs being matched for 333 (95.9%) patients. Donor gender, cytomegalovirus status and ABO incompatibility did not influence the five-year overall survival. In univariate analyses, overall survival was negatively influenced by the presence of acute graft-versus-host disease (33% vs. 47%, respectively; p-value = 0.04), unrelated transplant (41.5% vs. 50.9%, respectively; p-value = 0.045) and donors aged over 40 years (41% vs. 52%, respectively; p-value = 0.03). Older donors were associated with a higher rate of acute (52% vs. 65.8%; p-value = 0.03) and chronic graft-versus-host disease (60% vs. 43%, respectively; p-value = 0.015). In multivariate analyses, acute graft-versus-host disease [relative risk (RR): 1.8; 95% confidence interval (CI): 1.1–29; p-value = 0.008] and older donors (RR: 1.6; 95% CI 1.11–2.24; p-value = 0.013) were associated with higher transplant-related mortality. Conclusions: In transplant patients, to have a donor older than 40 years of age seems to significantly increase the incidence of acute and chronic graft-versus-host disease and transplant-related mortality with no impact on disease-free survival and overall survival. In spite of the rather small cohort of patients, these findings are similar to what is described in the literature suggesting that a younger donor should be chosen whenever possible.

Resumo em Inglês:

ABSTRACT Background: Reticulocytes are immature red blood cells containing RNA remnants. Their population kinetics has been documented under various in vivo and in vitro conditions, including after storage of red blood cells in blood banks. The purpose of this study was to describe the influence of blood bank storage on the kinetics of reticulocyte disappearance by in vitro culturing. Method: Samples of reticulocyte-enriched fractions (Percoll density-gradient) were obtained over different storage times from six red blood cell units stored in additive solution-1 (AS-1). Reticulocyte fractions were then cultured in enriched media at 37 ºC and analyzed by flow cytometry with thiazole orange taking into account hemolysis. Results: Density-gradient enriched reticulocyte fractions were obtain from standard red blood cell units with <1% of reticulocytes. An exponential drop of reticulocytes was observed in cultures. The time taken for reticulocyte disappearance in cultures was shorter with increased blood bank storage time (144 ± 46 h at 0.5 weeks of storage and 15 ± 14 h in the sixth week). High fluorescence reticulocytes disappeared completely in 42.5 ± 8.5 h, medium fluorescence reticulocytes in 73.4 ± 20.8 h and low fluorescence reticulocytes in 269.9 ± 98.8 h in red blood cell units stored for half a week. These times significantly decreased in red blood cell units stored for more time. Conclusion: In vitro reticulocyte disappearance was significantly faster after prolonged storage of red blood cell units at 4 ºC. The in vitro half-life at 0.5 weeks of storage was not significantly different from the values reported for fresh venous blood, but after the sixth week of storage, the half-lives were shorter. The possible explanation is that blood bank storage does not cause irreversible damage to the human reticulocyte maturational machinery.

Resumo em Inglês:

ABSTRACT Background: Anemia during childhood is one of the biggest public health problems worldwide, including Brazil. Insufficient or abnormal production of hemoglobin, loss of iron and excessive destruction of red blood cells are the most common causes of anemia. Among the reasons of anemia, iron deficiency accounts for 50% of anemia cases in developing countries. Affected individuals present a wide range of clinical problems, including delayed neuropsychomotor progression, impaired cellular immunity and reduction of intellectual capacity. This study aimed to evaluate the prevalence of anemia in children attending public schools in the metropolitan region of Curitiba, Paraná, Brazil. Method: A retrospective study was conducted of 409 children aged 8–12 years old included in an extension project of the Universidade Federal do Paraná. The results of complete blood count and hemoglobin electrophoresis of all children were evaluated. Anemia was considered when the hemoglobin levels were <11.5 g/dL. Results: The prevalence of anemia was found to be 2.2% of the population studied, with hypochromic microcytic anemia being the most common type. Seven children had sickle cell trait and one had β-thalassemia. Conclusion: The prevalence of anemia in this study was considered normal according the World Health Organization classification, which is different from the data found in other Brazilian regions.

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ABSTRACT Background: The Brazilian elderly population is growing exponentially, making prevention and treatment of chronic diseases a priority in this age group. Anemia in older adults is underdiagnosed, undervalued and associated with high morbimortality. Objective: To assess the prevalence of anemia in the elderly residents of a long-term care institution and to correlate this with individual patient history, the use of polypharmacy and mortality. Method: A retrospective study was carried out of data extracted from medical records of patients treated in 2014 at the Hospital Geriátrico e de Convalescentes Dom Pedro II under the Preventive Actions Program. Results: Data were collected from 88 female (48%) and 95 male (52%) elderly residents at a long-term care institution. Patient ages ranged from 60 to 102 years with a mean age of 76.3 years. Overall, 76 participants were diagnosed with anemia, representing 41% of the sample. Of those diagnosed, 35 were women (46%) and 41 were men (54%). Conclusion: Anemia in the elderly is a clinical condition associated with increased morbimortality. However, the disorder remains underdiagnosed, resulting in higher risks for older adults. The present study found 76 patients with anemia among the 183 residents at the long-term care institution. The patient profile of this population with anemia is non-smokers, male, aged between 70 and 79 years, with normochromic/normocytic anemia and taking multiple medications.

Resumo em Inglês:

ABSTRACT Objective: This study aimed to investigate the relationship between hematological parameters, serum iron, and vitamin B12 levels in adult hospitalized Palestinian patients infected with Helicobacter pylori. Methods: This case–control study included 150 adult (18–50 years old) patients infected with H. pylori and 150 healthy adults. A complete blood count was performed, and serum iron and vitamin B12 levels of the patients were measured, statistically analyzed and compared with the control group. All parameters in cases were reassessed after the triple treatment of omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d. for 14 successive days. The triple treatment was the same for males and females. Results: The results revealed that the mean levels of hemoglobin, red cell count, white cell count and hematocrit were significantly lower and the red blood cell distribution width significantly higher in cases compared to controls, while no significant differences were found for mean corpuscular volume, mean corpuscular hemoglobin and platelet count. Serum vitamin B12 and iron levels were significantly lower in cases compared to controls (262.5 ± 100.0 vs. 378.2 ± 160.6 pg/mL and 71.6 ± 24.8 vs. 80.1 ± 20.7 µg/dL, respectively). Vitamin B12 and serum iron increased significantly and was restored to close to normal levels after medical treatment. Conclusions: H. pylori infection appears to cause decreases in vitamin B12, iron levels and some hematological parameters. However, these were almost normalized after treatment with omeprazole, amoxicillin and clarithromycin. H. pylori is associated with vitamin B12 and iron deficiency, thus, this may be a useful marker and a possible therapeutic agent of anemic patients with gastritis.

Resumo em Inglês:

ABSTRACT Cerebrovascular disease, particularly stroke, is one of the most severe clinical complications associated with sickle cell disease and is a significant cause of morbidity in both children and adults. Over the past two decades, considerable advances have been made in the understanding of its natural history and enabled early identification and treatment of children at the highest risk. Transcranial Doppler screening and regular blood transfusions have markedly reduced the risk of stroke in children. However, transcranial Doppler has a limited positive predictive value and the pathophysiology of cerebrovascular disease is not completely understood. In this review, we will focus on the current state of knowledge about risk factors associated with ischemic stroke in patients with sickle cell disease. A search of PubMed was performed to identify studies. Full texts of the included articles were reviewed and data were summarized in a table. The coinheritance of alpha-thalassemia plays a protective role against ischemic stroke. The influence of other genetic risk factors is controversial, still preliminary, and requires confirmatory studies. Recent advances have established the reticulocyte count as the most important laboratory risk factor. Clinical features associated with acute hypoxemia as well as silent infarcts seem to influence the development of strokes in children. However, transcranial Doppler remains the only available clinical prognostic tool to have been validated. If our understanding of the many risk factors associated with stroke advances further, it may be possible to develop useful tools to detect patients at the highest risk early, improving the selection of children requiring intensification therapy.

Resumo em Inglês:

ABSTRACT Hemoglobin is an essential biological component of human physiology and its production in red blood cells relies upon proper biosynthesis of heme and globin protein. Disruption in the synthesis of these precursors accounts for a number of human blood disorders found in patients. Mutations in genes encoding heme biosynthesis enzymes are associated with a broad class of metabolic disorders called porphyrias. In particular, one subtype – erythropoietic protoporphyria – is caused by the accumulation of protoporphyrin IX. Erythropoietic protoporphyria patients suffer from photosensitivity and a higher risk of liver failure, which is the principle cause of morbidity and mortality. Approximately 90% of these patients carry loss-of-function mutations in the enzyme ferrochelatase (FECH), while 5% of cases are associated with activating mutations in the C-terminus of ALAS2. Recent work has begun to uncover novel mechanisms of heme regulation that may account for the remaining 5% of cases with previously unknown genetic basis. One erythropoietic protoporphyria family has been identified with inherited mutations in the AAA+ protease ClpXP that regulates ALAS activity. In this review article, recent findings on the role of ClpXP as both an activating unfoldase and degrading protease and its impact on heme synthesis will be discussed. This review will also highlight the role of ClpX dysfunction in erythropoietic protoporphyria.