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ABSTRACT Introduction The West African region has been lagging in terms of the availability of, and accessibility to, safe blood. According to the 2016 World Health Organization (WHO) Global Status Report on Blood Safety and Availability, none of the West African countries met the WHO benchmark of 10 blood units per 1000 inhabitants. This study is aimed at discussing the blood transfusion status of West African countries in the pre-COVID-19 period and analyze the capacity to respond to the COVID-19 blood crisis, as well as to outline the panacea. Methods Secondary data were extracted from published reports, journal articles and web pages, reviewed and analyzed. Result All the West African countries have recorded confirmed COVID-19 cases and deaths. The confirmed cases have reached 55,697, with 1069 deaths and a fatality rate of 1.9%, as of June 17, 2020. The assessed countries lagged in most of the WHO benchmarks for effective blood transfusion services. Conclusion Blood transfusion services in the West African region lacked the basic benchmark practice and policy, are not coordinated and may find it hard to tackle the blood transfusion crisis created by the COVID-19 pandemic.

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ABSTRACT Introduction The novel coronavirus disease has disrupted blood transfusion services worldwide. Despite blood transfusion services taking several precautionary measures to minimize the risks of COVID-19 during blood donations, donors became anxious regarding the risk of the COVID-19 infection during the donation and the blood transfusion services was facing the inevitable hazard of blood shortage. Methods The study was conducted at a tertiary care oncology hospital-based blood transfusion services and included analysis of blood donations, packed red blood cell units requirements, and packed red blood cell inventory in the pre lockdown and lockdown phase. New COVID-19 standard operating procedures with enhanced safety guidelines and donor confidence-building measures were implemented at the blood transfusion services. Results The total number of average monthly blood donations decreased in lockdown but the decrease was not statistically significant (238.5 vs. 197.8, P = 0.391). The requisitions for the packed red blood cell cross-matches (722.5 vs. 329.0, P = 0.001) and the packed red blood cell utilization (176.5 vs. 103.3, P = 0.028) for the hospital patients also decreased significantly due to the lockdown. In the lockdown phase, an expressive number of packed red blood cell units were outdated due to the unprecedented fall in the number of patients. In the post-lockdown phase, the packed red blood cell inventory was optimized with decreased outdating via a comprehensive approach. A special emphasis was given to the in-house donations. A second partial lockdown also decreased the blood donations. Conclusion Confidence-building in blood donors and the resolution of logistical issues were crucial for the efficient packed red blood cell inventory management in the lockdown. Implementation of COVID-19 preventive measures helped in the blood donor and blood transfusion services staff safety.

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ABSTRACT Background Carica papaya Linn. has high nutraceutical and pharmacological values. The leaves possess antimicrobial, anti-tumor and antioxidant properties. They are used to treat thrombocytopenia during dengue fever and the leaf extract is commercially available as tablets under the name Caripill™ (MicroLabs, Bengaluru). Nevertheless, platelet transfusion is recommended in severe cases of thrombocytopenia, but the platelet storage is limited to 5-7 days at 22−24 °C. Reducing oxidative stress (OS) during platelet storage might help in prolonging the shelf-life, since the OS is known to cause platelet storage lesion. Hence, this study investigated the effects of Caripill™ as an additive in Tyrode's buffer during extended platelet storage. Methods Platelets isolated from 4 months old male Wistar rats were stored with Caripill™ (50 and 100 µg/ml) at 22 °C for 12 days. Platelet functional and metabolic markers and various OS markers were analyzed on days 0, 4, 8 and 12. Results Caripill™ (50 and 100 µg/ml) maintained platelet functions and lactate dehydrogenase, elevated nitrites, reduced glucose consumption, protected proteins and up-regulated the antioxidant enzymes. However, the CP100 up-regulated catalase from day 4, elevated nitrites from day 8, prevented the formation of secondary products of lipid peroxidation and increased the total antioxidant capacity on day 4. Conclusions Caripill™ reduced platelet storage lesion up to day 8 of storage. Results suggest that a higher concentration of Caripill™ was more effective in combating the oxidative damage during platelet storage. This study throws light on the beneficial effects of Caripill™ in combating oxidative stress during platelet storage.

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ABSTRACT Background Acute lymphoblastic leukemia (ALL) is the most common malignancy in children characterized by the overproduction and accumulation of immature lymphoid cells in the bone marrow and peripheral blood. The BMI-1 is an important component of the Polycomb Repressive Complex-1 (PRC1). It is an important molecule for the self-renewal of hematopoietic stem cells (HSCs). The BMI-1 expression is generally high in HSCs and decreases after cell differentiation. The BMI-1 is required for the maintenance of normal and cancer stem cells and has been reported as an oncogene in various tumors. The NANOG is a homeodomain transcription factor responsible for maintaining the stem cell compartment at the blastocyst stage of developing embryos. The NANOG gene has been proven to be transcribed in CD34+ cells and different leukemic cells. Methods The ribonucleic acid (RNA) was extracted from the peripheral blood mononuclear cells (PBMNCs) of 30 pediatric ALL patients (16 B-ALL and 14 T-ALL) and 14 healthy controls. The Bmi-1 and NANOG expression levels were determined using the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Results Compared to normal controls, patients with ALL exhibited upregulated levels of Bmi-1 (p = 0.03). Patients who overexpressed Bmi-1 and NANOG displayed a significantly worse survival than low-expressing patients (hazard ratio (HR) 5.74, 95% confidence interval (CI):1.48-22, p = 0.012 and HR 3.8, 95% CI:1.009-14.3, p = 0.048, respectively). Conclusions Taken together, these data suggest that the Bmi-1 and NANOG might serve as a novel survival predictor in ALL patients. Our observation also suggests that the Bmi-1 and NANOG could serve as new therapeutic targets for treatment of pediatric ALL.

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ABSTRACT Objectives The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41 °C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC) < 370 g/L and in samples with the MCHC > 370 g/L, in the presence of cold agglutinins. Methods In this study, 60 blood samples (group 1) with the MCHC < 370 g/L (without cold agglutinins) and 78 blood samples (group 2) with the MCHC > 370 g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). Results The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. Conclusions The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370 g/L.

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ABSTRACT Introduction Sickle cell disease (SCD) is a monogenic disease and it is estimated that 300,000 infants are born annually with it. Most treatments available are only palliative, whereas the allogeneic hematopoietic stem cell transplantation offers the only potential cure for SCD. Objective Generation of human autologous cells, when coupled with induced pluripotent stem cell (iPSC) technology, is a promising approach for developing study models. In this study, we provide a simple and efficient model for generating hematopoietic cells using iPSCs derived from a sickle cell anemia patient and an inexpensive in-house-prepared medium. Method This study used iPSCs previously generated from peripheral blood mononuclear cells (PBMCs) from a patient with sickle cell anemia (iPSC_scd). Hematopoietic and erythroid differentiation was performed in two steps. Firstly, with the induction of hematopoietic differentiation through embryoid body formation, we evaluated the efficiency of two serum-free media; and secondly, the induction of hematopoietic stem/progenitor cells to erythroid progenitor cells was performed. Results The patient-specific cell line generated CD34+/CD45+ and CD45+/CD43+ hematopoietic stem/progenitor cells and erythroid progenitors, comprising CD36+, CD71+ and CD235a+ populations, as well as the formation of hematopoietic colonies, including erythroid colonies, in culture in a semi-solid medium. Conclusion In conjunction, our results described a simple serum-free platform to differentiate human the iPSCs into hematopoietic progenitor cells. This platform is an emerging application of iPSCs in vitro disease modeling, which can significantly improve the search for new pharmacological drugs for sickle cell disease.

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ABSTRACT Introduction Mutations affecting genes involved in oxidative and signaling pathways may be associated with kidney disease in sickle cell anemia. We determined the allele and genotype frequencies of some polymorphisms in the promoter regions of the Heme Oxygenase-1 (HMOX1) [rs2071746 (A > T) and (GT)n repeats, short (S) and long (L) alleles] and Bone Morphogenetic Protein Receptor type-1B (BMPR1B) [rs17022863 (A > G), rs4331783 (A > G) and rs1470409 (A > G)] genes in 75 adult patients with sickle cell anemia and 160 healthy controls and investigated whether these polymorphisms may influence the estimated glomerular filtration rate for the patients. Methods The single nucleotide polymorphisms were genotyped using the TaqMan assays, the HMOX1(GT)n repeats were determined by polymerase chain reaction fragment size analysis and the estimated glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula. Results Regarding the HMOX1rs2071746, the estimated glomerular filtration rate median was significantly higher in TT patients (p = 0.019), including when TT was compared with AT + AA (p = 0.009); for the (GT)n repeats, the estimated glomerular filtration rate medians of SS, SL and LL significantly differed (p = 0.009), being the LL estimated glomerular filtration rate median significantly higher, when compared with the LS + SS (p = 0.005). These results suggest that both the homozygotes, TT for rs2071746 and LL for (GT)n repeats, lead to a higher risk of developing renal complications. Concerning the BMPR1B, the frequencies of GG for rs17022863 and AA for rs4331783 were significantly higher in patients than in controls (p = 0.002 and p = 0.008, respectively), however no association with estimated glomerular filtration rate was found. Conclusion These results contribute to a better understanding of the genetic factors related to the development of nephropathy in sickle cell anemia patients.

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ABSTRACT Introduction Multiple cause of death methodology enhances mortality studies beyond the traditional underlying cause of death approach. Aim: This study aims to describe causes of death and mortality issues related to haemophilia with the use of multiple-cause-of-death methodology. Methods: Annual male haemophilia mortality data was extracted from the public multiple-cause-of-death databases of the Mortality Information System, searching deaths included in rubrics D66 "hereditary factor VIII deficiency" (haemophilia A), and D67 "hereditary factor IX deficiency" (Haemophilia B) of the International Classification of Diseases, Tenth Revision, and processed by the Multiple Cause Tabulator. Results: In Brazil, from 1999 to 2016, a total of 927 male deaths related to haemophilia occurred during the 18 year period, of which 418 (45,1 %) as underlying cause, and 509 (54,9 %) as associated cause of death. The leading associated cause of 418 deaths of haemophilia as underlying cause was hemorrhage (52.6%), half of which intracranial hemorrhage. Infectious and parasitic diseases accounted for 40,5% as the underlying causes of 509 deaths where haemophilia was an associated cause, where human immunodeficiency virus disease prevailed, however falling from 37,0% to 19.7%, and viral hepatitis increased from 6.0% to 7.9%; diseases of the circulatory system, increased from 13.5% to 18.4%, including intracranial hemorrhage from 5.7% to 7.0%, and neoplasms, from 8,5% to 13.2%, respectively from 1999-2007 to 2008-2016, followed as main underlying causes. Conclusion: Hemorrhages, mainly intracranial hemorrhage, human immunodeficiency virus disease, and viral hepatitis are the chief prevention goals aiming at the control of haemophilia mortality.

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ABSTRACT Background Transfusion of platelets (PLTs) with high ABO antibody titres can pose a risk of hemolysis if the unit crosses the ABO type. The PLTs stored in the platelet additive solution (PAS) remove asubstantial fraction of plasma and replace it with an isotonicbuffered solution.We aimed to assess the difference in anti-A/B antibody levels in Groups O, A and B apheresis platelets (APs) suspended in plasma and PAS. Methodology Apheresis donors are categorized into two groups, Plasma (Group I) and PAS (Group II), each blood group (A, B and O) had 20 samples. The anti-A/B(IgM)antibody levels were recorded from the AP donor (Group II) and from the AP units for both groups. The reduction in the anti-A/B(IgM) antibody levels in the APs suspended in the PAS for each blood group was determined. Results The median anti-A titres in blood Groups B (p = 0.009) and O (p = 0.005) was significantly lower in Group II. However, the difference in anti-B levels was not significant in the blood groups A (p = 0.057) and O (p = 0.205). The median level of reduction in IgM antibody titres across donor samples and the PAS-stored platelets was two-fold. The regression showed a level of reduction in antibody titres which can be explained by baseline donor antibody titres in blood groups A and B compared to blood group O. Conclusion The medianABO antibody titres were lower in APs suspended in PAS than in plasma. Addition of the PAS significantly lowered the IgM antibody titres by twofold, compared to plasma.

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ABSTRACT Introduction Multiple myeloma is a progressive and incurable hematological disease characterized by disordered and clonal multiplication of plasmacytes in the bone marrow. The main clinical manifestations are caused by the presence of neoplastic cells in bone tissue, as well as the excessive production of immunoglobulins and normal humoral immunity suppression. Daratumumab is an anti-CD38 monoclonal antibody that has promising results in managing the multiple myeloma disease. Objective This study aimed to investigate the scientific evidence concerning the impact of the cytomegalovirus infections in the daratumumab treatment course in extensively pretreated multiple myeloma patients. Method To this end, an integrative literature review was performed in different databases, comprising a 5-year period. Results The studies analysis revealed that the cytomegalovirus infection reactivation can occur during the use of daratumumab in multiple myeloma patients previously treated, which led to treatment discontinuation, compromised the drug efficacy and favored the disease progression. Moreover, it was observed that even with prophylactic antiviral therapy there was an infection reactivation in some cases, as well as deaths, in more severe situations. Conclusion Thus, even considering that few reports on such a topic are available in the scientific literature, the present review showed that cytomegalovirus reactivation can impair daratumumab therapy, mainly in multiple myeloma patients heavily pretreated. In addition, this study could contribute as a tool for the clinical decision and management of adverse effects in medical practices, demonstrating the importance of patient monitoring for the possibility of cytomegalovirus reactivation in heavily pretreated myeloma patients.

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ABSTRACT This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation.In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low).Once stratified, the treatment of the CV risk factors should be administered. If the patient presents risk factors, such as hypertension, diabetes, renal disease, smoking and hypercholesterolemia, the evaluation and initial treatment may be done by the hematologist, being an option the request for evaluation by a specialist. If the patient has a history of previous CV disease, we recommend referral to a specialist. As the CV risk score is dynamic and the control of risk factors can reduce the patient risk, this expert consensus recommends that the re-evaluation of the CV risk after the baseline should be performed at 3 months, 6 months and 12 months. After this period, it should be done annually and, for specific patients, at the clinician's discretion.The evaluation of the baseline CV risk and the safe administration of a TKI allow the patient to benefit from the maximum treatment, avoiding unwanted effects.

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ABSTRACT The COVID-19 pandemic has pushed the world towards social, economic, and medical challenges. Scientific research in medicine is the only means to overcome novel and complex diseases like COVID-19. To sum up the therapeutic wild-goose chase, many available antivirals and repurposed drugs have failed to show successful clinical evidence in patient recovery, several vaccine candidates are still waiting in the trial pipelines and a few have become available to the common public for administration in record time.However, with upcoming evidence of coronavirus mutations, available vaccines may thrive on the spirit of doubt about efficacy and effectiveness towards these new strains of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2). In all these collective uncertainties, plasma therapy has shown a ray of hope for critically ill patients. To date, with very few published case studies of convalescent plasma in COVID-19, there are two school of thought process in the scientific community regarding plasma therapy efficiency and this leads to confusion due to the lack of optimal randomized and controlled studies.Without undertaking any robust scientific studies, evidence or caution, accepting any therapy unanimously may cause more harm than good, but with a clearer understanding of SARS-CoV2 immunopathology and drug response, plasma therapy might be the silver lining against COVID-19 for the global community.