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Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

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Abstract Introduction Audit and education are essential pre-requisites in the review and update of blood transfusion practices. Although standard guidelines on appropriate utilization of blood components exists, erroneous use of blood components with no justification still continues. This study evaluates appropriateness of blood transfusion in obstetric settings and identifies key areas requiring educational intervention to improve blood transfusion practice toward the evidence-based at our hospital. Method This was a prospective observational study on the analysis of blood transfusion requisition forms for obstetric patients before and after educational intervention, performed in two Phases from September 2011 to August 2012 and October 2012 to September 2013. The appropriateness of blood utilization was assessed against the Royal College of Obstetricians and Gynecologists Guidelines for blood transfusion and Green-Top Guideline no. 47. Data required for the study were obtained from department records and statistical analysis was performed using the SPSS, version 20 (IBM, USA). Results The total transfusion episodes were 214 in 51 patients and 181 in 43 patients in Phases 1 and 2, respectively. Fresh frozen plasma was the most misused blood component, next to whole blood in Phase 1. However, appropriate utilization of components, including cryoprecipitate (6.6%), reduction in whole blood (34.5-14.4%) and single unit transfusion (23.3-18.2%) were observed in Phase 2. Inappropriate use of blood components, namely, packed red blood cells and fresh frozen plasma dropped significantly (p < 0.05) from 29.7% to 13.1% and 45.1% to 22.5%, respectively, with the exclusion of platelet concentrate (33.3-20.6%, p-value 0.414). Conclusion Audit and targeted education helped in optimizing transfusion practices in the obstetric setting.

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Abstract Introduction Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (β-thal). Therefore, the single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of β-thal phenotypic manifestations. Objective and method In order to better understand the genotypic and/or allelic distributions among β-thal patients, we evaluated 83 β-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among β-thal homozygotes. Results We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the β-thal group (p< 0.0001 and p= 0.00014, respectively). The most common clinical manifestations found among β-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences. Conclusion Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the β-thal homozygotes studied.

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Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

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Abstract Introduction Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood. Objective The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA. Method It was a cross-sectional study on adult participants with SCA followed at Fundação Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ± 10.7 years); 30 had LU and 57 were controls without LU. Results Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU. Conclusion In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA.

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Abstract Introduction There is a demand to update national mortality trends data related to sickle cell disease (SCD) in Brazil. This study describes causes of death and mortality issues related to SCD using the multiple-cause-of-death methodology. Methods The annual SCD mortality data was extracted from the public databases of the Mortality Information System by researching deaths in rubric D57 “sickle-cell disorders” of the International Classification of Diseases, Tenth Revision and processed by the Multiple Cause Tabulator. Results From 2000 to 2018 in Brazil, a total of 9817 deaths related to SCD occurred during the 19-year period, as the underlying cause in 6924 (70.5%) and as the associated cause of death in 2893 (29.5%). The mean and median ages at death during the entire period were significantly lower for males, 29.4 (±19.6) and 27.5 (15.5-41.5), respectively, than for females, 33.3 (±20.3) and 31.0 (19.5-46.5), respectively. The leading SCD overall associated causes of death were septicemias (32.1%), followed by pneumonias (19.4%) and respiratory failure (18.2%). On certificates with SCD as an associated cause, the underlying causes of death were circulatory system diseases (8.7%), followed, in males, by digestive system and infectious diseases and respiratory system failures, while in females, maternal deaths, included in the chapter on pregnancy, childbirth and the puerperium, accounting for 4.6% of female deaths, were succeeded by digestive system and infectious diseases. Conclusion This study revised mortality data on death rate trends, underlying and associated causes of death, age at death and regional distribution of death in Brazil.

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Abstract Introduction Sickle cell disease is an autosomal recessive genetic disease caused by a single point mutation in the β-globin chain of the hemoglobin. It has been recognized by the World Health Organization as a public health priority since 2006. Methods The Scopus database was used in this study with the search descriptors: “sickle cell” and “sickle cell disease”. We applied common bibliometric indicators to evaluate the trend in scientific literature in sickle cell disease research. Results We retrieved a total of 19,921 pieces of scientific literature in the repertoire from 1997 to 2017. The Price law was fulfilled in the trend of production of scientific literature on SCD as the growth of scientific literature was more exponential (r = 0.9751; r2 = 0.9509) than linear (r = 0.9721; r2 = 0.9449). We observed a duplication time of 4.52 years. The Bradford core was made up of 69 journals with Blood at the top, publishing the greatest number of articles. The most productive institutions were mostly United States agencies and hospitals. The United States was the most productive country. The National Institute of Health was the most productive institution and also had the highest number of citations. Vichinsky E was the most productive author, while the most cited article was published by Circulation. Conclusion The growth of scientific literature in Sickle cell disease was found to be high. However, the exponential growth trend shows a “yet-to-be-explored” area of research. This study will be useful for physicians, researchers, research funders and policy-cum-decision makers.

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Abstract Introduction The isolation of captured peripheral blood mononuclear cells (PBMNCs) from leukoreduction filters (LRFs) can be of great importance in terms of bringing the lost cells back into use. Objective The aim of this study was to evaluate various methods based on their potential to recover the peripheral blood cells from LRFs with a focus on mononuclear cells (MNCs). Method For cell isolation from LRFs, three distinct methods (back-flushing, direct and vacuum pump) were compared through the calculation of the yield of isolated MNCs. The viability of extracted cells was determined by the flow cytometry technique. Moreover, the recovered MNCs were characterized regarding the presence of blood stem cell purification. The cell culture, microscopic observation, and immunophenotyping were employed to characterize the blood stem cells (hematopoietic, mesenchymal and progenitor endothelial stem cells). Results The yield of isolation obtained in the back-flushing, direct and vacuum pump methods were 17.7 ± 1.28, 17.3 ± 0.96 and 21.2 ± 0.90 percent, respectively. Although the highest potential for total blood cell recovery belonged to the vacuum pump method, the lowest cell viability (85.73 ± 4.84%) was observed in this method. However, the isolation process of the back-flushing and direct methods had less effect on cell viability. The characterization of the isolated MNCs displayed that the dominant positive phenotype was for CD34/CD45, indicating hematopoietic stem cells. In addition, the endothelial stem/progenitor cells were significantly detected as CD31/CD133 positive cells. Conclusion According to our results and considering the safety and efficiency potential of each of the applied methods, the back-flushing in comparison with the other methods can be considered a suitable procedure for MNC isolation from LRFs.

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Abstract Introduction Convalescent Plasma therapy is one of the therapeutic strategies that has been used for patients with the Covid-19 disease. Implementing a program with national extension to supply hospitals with this blood component is a great challenge mainly in a middle-income economy. Objectives Our objective was to develop and implement a Covid-19 Convalescent Plasma Program which met established quality standards and was adapted to a reality of limited resources. Methods A multicentric convalescent plasma collection program was developed and implemented, based on four main sequential procedures: selective donor recruitment, pre-donation antibody screening (Anti-SARS-CoV-2- Chemiluminescence IgG Abbott), convalescent plasma collection by apheresis or whole-blood processing and distribution to the hospitals according to local demand. Results From the 572 candidates submitted to the pre-donation antibody screening, only 270 (47%) were considered eligible for plasma donation according to the established criteria. Higher levels of total antibody were associated with the donor age being above 45 years old (p= 0.002), hospital admission (p= 0.018), and a shorter interval between the diagnosis of the SARS-CoV-2 infection and plasma donation (p < 0.001). There was no association between the ABO and Rh blood groups and their antibody levels. Of the 468 donations made, 61% were from the collection of whole-blood and 39%, from apheresis. The Covid-19 Convalescent Plasma units obtained were distributed to 21 different cities throughout the country by air or ground transportation. Conclusion The implementation of a Covid-19 Convalescent Plasma program in a continental country with relatively scarce resources is feasible with alternative strategies to promote lower cost procedures, while complying with local regulations and meeting quality standards.

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ABSTRACT Introduction The pro-inflammatory immune response underlies severe cases of COVID-19. Antigens of the Duffy blood group systems are receptors for pro-inflammation chemokines. The ACKR1 c.-67T>C gene variation silences the expression of Duffy antigens on erythrocytes and individuals presenting this variant in homozygosity have impaired inflammatory response control. Our aim was to evaluate the association between the ACKR1 c.-67T>C and the severity of COVID-19. Methods This was a retrospective single-center case-control study, enrolling 164 participants who were divided into four groups: 1) Death: COVID-19 patients who died during hospitalization; 2) Hospital Discharge: COVID-19 patients who were discharged for home after hospitalizations; 3) Convalescent Plasma Donors: COVID-19 patients who were not hospitalized, and; 4) Controls: patients with diagnosis other than COVID-19. Patients were genotyped for the ACKR1 c.-67T>C (FY*02 N.01 allele) and the frequency of individuals presenting the altered allele was compared between the groups. Results The groups significantly differed in terms of the percentage of patients presenting at least one FY*02N.01 allele: 36.8% (Death group), 37% (Hospital Discharge group), 16.1% (Convalescent Plasma group) and 16.2% (Control group) (p= 0.027). The self-declared race (p < 0.001) and the occurrence of in hospital death (p= 0.058) were independently associated with the presence of the FY*02N.01 allele. Hypertension (p < 0.001), age (p < 0.001) and the presence of at least one FY*02N.01 allele (p= 0.009) were independently associated with the need for hospitalization. Conclusion There is a suggestive association between the presence of the FY*02N.01 and the severity of COVID-19. This may be a mechanism underlying the worse prognosis for Afro-descendants infected with SARS-CoV-2.

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Abstract Introduction The novel SARS-CoV-2 infection has been spreading around the world since January 2020 causing the Corona Virus Disease 2019. Leukopenia, lymphopenia and hypercoagulability with elevated D- Dimers have been described in COVID-19 patients to date. This study aimed to clarify if some blood parameters can be used as biomarkers to facilitate diagnosis and establish prognosis. Methods: We selected patients who had tested positive for SARS-CoV-2 and had had a hemogram performed between the March 15 and April 15, 2020. Socio-demographic and analytical data were obtained from 274 patients at admission in two Portuguese public hospitals. We then analyzed the hemogram parameters at admission in the intensive care and collected data on patient survival during the SARS-CoV-2 disease follow-up. The data were analyzed using appropriate statistical tests. Results: Patients requiring the intensive care unit (ICU) present an increase in leukocytes and neutrophils (+3.1 × 109/L and +6.4 × 109/L, respectively), a lymphocyte decrease and a platelet rise (-1.6 × 109/L and +60.8 × 109/L, respectively). The erythrocytes, hemoglobin and median globular volume tend to decrease (-0.5 × 1012, - 1.2 g/dL; -3 fL, respectively). The lactic acid dehydrogenase (LDH) at admission was significantly higher (+58.1 U/L). The age, sex, platelets, lymphocyte count neutrophil counts, neutrophil/lymphocyte ratio, erythrocytes and cell hemoglobin concentration mean (CHCM) are independently associated with mortality (odds ratio (OR) = 0.046, p < 0.001; OR = 0.2364, p= 0.045; OR = 9.106, p= 0.001; OR = 0.194, p= 0.033; OR = 0.062, p= 0.003; OR = 0.098, p= 0.002; OR = 9.021, p < 0.001; OR = 7.016, p= 0.007, respectively). Conclusion The hematological data at admission in the health care system can predict the mortality of the SARS-CoV-2 infection and we recommend its use in the clinical decisions and patient prognosis evaluation.

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Introduction The coronavirus disease-2019 (COVID-19) has emerged as a novel infection which has spread rapidly across the globe and currently presents a grave threat to the health of the cancer patient. Objective The aim of this meta-analysis was to evaluate the proportion of hematological cancer patients with the SARS-CoV-2 infection during the COVID-19 pandemic. Method A comprehensive literature review was performed on PubMed, Web of Science, Scopus, EKB SciELO, SID, CNKI and Wanfang databases to retrieve all relevant publications up to January 31, 2021. Observational studies, consecutive case-series and case-control studies were included. The proportion for hematological cancer patients with COVID-19 was estimated using the odds ratios (ORs) and 95% confidence interval (95% CIs). Results Fourteen studies with a total of 3,770 infected cancer patients and 685 hematological cancer cases with COVID-19 were selected. Combined data revealed that the overall proportion of hematological cancer patients with COVID-19 was 16.5% (95% CI 0.130 - 0.208, p ≤ 0.001). The stratified analysis by ethnicity showed that the proportion was 18.8% and 12.4% in Caucasian and Asian hematological cancer patients with COVID-19, respectively. Moreover, subgroup analysis by country of origin showed that its proportion was the highest in the United Kingdom (22.5%), followed by France (17.1%) and China (8.2%). Conclusion This meta-analysis result indicated that the proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic was 16.5%. Further larger sample sizes and multicenter studies among different ethnic groups are necessary to get a better assessment of the proportion.

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Abstract Introduction The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.