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The article presents the modern data of from national and foreign literature on the problems associated with the influence of the type and intensity of physical activity on the state of red blood cells, both in athletes and in untrained subjects. The article emphasizes the role of intensive training in the damage to the erythrocyte membrane and describes the possible mechanisms of these disorders in athletes of different sports, as well as ways to restore them. The article dwells upon the possibilities to correct red blood cell disorders in various pathologies with physical exercises.

Disorders affecting red blood cells (RBCs) are uncommon yet have many important physiologic considerations for patients undergoing cardiac surgery. RBC disorders can be categorized by those that are congenital or acquired, and further by disorders affecting the RBC membrane, hemoglobin, intracellular enzymes, or excessive RBC production. A foundational understanding of the physiologic derangement for these disorders is critical when considering perioperative implications and optimization, strategies for cardiopulmonary bypass, and the rapid recognition and treatment if complications occur. This review systematically outlines the RBC disorders of frequency and relevance with an emphasis on how the disorder affects normal physiologic processes, a review of the literature related to the disorder, and the implications and recommendations for patients undergoing cardiac surgery.

Hydroxychloroquine has been used worldwide as a first-line treatment for patients hospitalized with COVID-19. Little is known about COVID-19 and its effects on patients with congenital red blood cell disorders. We report a case of haemolytic anaemia in a 32-year-old patient and a fortuitous highlighting of G6PD deficiency. We reviewed the literature to assess the risk of hydroxychloroquine use in this context. LEARNING POINTS: A rapid drop in haemoglobin in COVID-19 patients should alert physicians to test for haemolytic anaemia and enzymopathies. Our review of the literature shows that use of hydroxychloroquine is safe in G6PD-deficient patients.

PV, NR and MMP contributed equally Introduction Patients with red blood cell disorders (RBCD), chronic life threating multisystemic disorders in their severe forms, are likely to be at increased risk of complications from SARS-Cov-2 (Covid-19), but evidence in this population is scarce due to its low frequency and heterogeneous distribution. ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting severe outcomes. Methods The ERN-EuroBloodNet registry was established in March 2020 by Vall d'Hebron Research Institute based on REDcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirmed that the exceptional case of the pandemic justifies the waiver of informed consent. The ERN-EuroBloodNet registry on RBCD and COVID-19 is endorsed by the European Hematology Association (EHA). Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 (severity grade, clinical manifestations, acute events, treatments, hospitalization, intensive care unit, death). For analysis of COVID-19 severity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Severe: pneumonia requiring oxygen/respiratory support and/or admission to intensive care unit. Continuous variables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical variables were analyzed using the Chi-square test or Fisher's Exact test. Relevant factors influencing disease or severity were examined by the logistic regression adjusted for age. Results As of June 2021, 42 medical centers from 10 EU countries had registered 373 patients: 191 Sickle cell disease (SCD), 156 Thalassemia major and intermedia (THAL) and 26 other RBCD. 84% of the SCD patients were reported by Spain, Belgium, Italy and The Netherlands and 92% of the THAL patients by Italy and Greece. The mean age of SCD was lower (22.5y) than of THAL (39.6y) with pediatric population accounting for 50.5% in SCD and 9% in THAL (p Age and BMI correlated with COVID-19 severity, as described in the general population (p=0.002, p Potential risk factors such as elevated ferritin, current chelation or history of splenectomy did not confer additional risk for developing severe COVID-19 in any patient group. Only diabetes as a comorbidity correlated with severity grade in SCD (p=0.011) and hypertension in THAL (p=0.014). While severe COVID-19 infection in SCD was associated with both ACS (p Overall, 14.8% RBC patients needed oxygen/respiratory support, 4.4% were admitted to ICU with an overall mortality rate of 0.8% (no deaths were registered in pediatric age), much lower than reported in other similar cohorts. Discussion Results obtained so far show that severe COVID-19 occurs at younger ages in more aggressive forms of SCD and THAL. Current preventive approaches (shielding, vaccinations) focus on age over disease severity. Our data highlights the risk of severe COVID-19 infection in some young patients, particularly those with SS/SB0 SCD, suggesting that immunization should be considered in this pediatric group as well. Results between similar sized cohorts of RBCD patients vary between each other and those presented here, highlighting the importance of collecting all of these small cohorts together to ensure adequate statistical power so that definitive risk factors (eg. age, genotype, comorbidities) can be reliably identified and used to guide management of patients with these rare disorders in the light of the ongoing pandemic. Figure 1 Figure 1. Disclosures Longo: Bristol Myers Squibb: Honoraria; BlueBird Bio: Honoraria. Bardón-Cancho: Novartis Oncology Spain: Research Funding. Flevari: PROTAGONIST COMPANY: Research Funding; ADDMEDICA: Consultancy, Research Funding; BMS: Research Funding; IMARA COMPANY: Research Funding; NOVARTIS COMPANY: Research Funding. Voskaridou: BMS: Consultancy, Research Funding; IMARA: Research Funding; NOVARTIS: Research Funding; ADDMEDICA: Consultancy, Research Funding; GENESIS: Consultancy, Research Funding; PROTAGONIST: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria; Celgene: Honoraria; Sanquin: Research Funding. Nur: Celgene: Speakers Bureau; Roche: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Beneitez-Pastor: Agios: Honoraria; Alexion: Honoraria; Novartis: Honoraria; Forma Therapeutics: Honoraria. Pepe: Chiesi Farmaceutici S.p.A: Other: no profit support; Bayer S.p.A.: Other: no profit support. de Montalembert: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees. Glenthøj: Agios: Consultancy; Novo Nordisk: Honoraria; Novartis: Consultancy; Alexion: Research Funding; Bluebird Bio: Consultancy; Bristol Myers Squibb: Consultancy; Saniona: Research Funding; Sanofi: Research Funding. Benghiat: Novartis: Consultancy; BMS: Consultancy. Labarque: Novartis: Consultancy; Bayer: Consultancy; Sobi: Consultancy; NovoNordisk: Consultancy; Octapharma: Consultancy. Diamantidis: Genesis Pharma: Honoraria; Uni-Pharma: Honoraria; Bristol Myers Squibb: Consultancy; IONIS Pharmaceuticals: Research Funding; NOVARTIS, Genesis Pharma SA: Research Funding. Kerkhoffs: Sanofi: Research Funding; Terumo BCT: Research Funding. Iolascon: Celgene: Other: Advisory Board; Bluebird Bio: Other: Advisory Board. Taher: Vifor Pharma: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy; Ionis Pharmaceuticals: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Colombatti: Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding. Mañú Pereira: Novartis: Research Funding; Agios Pharmaceuticals: Research Funding.

In red blood cell (RBC) disorders, such as sickle cell disease, hereditary spherocytosis, and diabetes, alterations to the size and shape of RBCs due to either mutations of RBC proteins or changes to the extracellular environment, lead to compromised cell deformability, impaired cell stability, and increased propensity to aggregate. Numerous laboratory approaches have been implemented to elucidate the pathogenesis of RBC disorders. Concurrently, computational RBC models have been developed to simulate the dynamics of RBCs under physiological and pathological conditions. In this work, we review recent laboratory and computational studies of disordered RBCs. Distinguished from previous reviews, we emphasize how experimental techniques and computational modeling can be synergically integrated to improve the understanding of the pathophysiology of hematological disorders. Keywords: red blood cell disorders; numerical modeling; laboratory approaches, National Institutes of Health (U.S.) (Grant U01HL114476), National Institutes of Health (U.S.) (Grant U01HL116323)

Keywords: haemoglobinopathies; malaria; miscarriage; red blood cell disorders; sickle cell disease

This paper investigates the possibility of rapid and accurate automated diagnosis of red blood cell disorders and describes a method to detect and classify malarial parasites in blood sample images acquired from light microscopes. Malaria is an infectious disease and is mainly diagnosed by microscopical evaluation of Giemsa stained blood smears. Since it causes a serious health problem, automation of the evaluation process is of high importance. The image classification system is designed to positively identify malaria parasite in thin blood smears. Morphological and novel threshold selection techniques are used to identify red blood cell and possible parasites present on microscopic slides. Image features based on colour, texture and the geometry of the cells and parasites are generated. Classifier based on back propagation feed forward neural network distinguishes between parasite infected and non-infected blood images.

Introduction Sickle cell disease (SCD) is a severe inherited red blood cell disorder with high morbidity requiring integrated comprehensive care. There are not many chronic diseases that primarily affect those from an often impoverished, minority background. Care delivery is complicated by disparities in healthcare regarding access. Cultural mismatches between providers and families also play a role. Healthcare access can be defined as the degree of fit between patients and the healthcare system (1, 2), and is described by four overlapping dimensions: physical accessibility, affordability, information accessibility and non-discrimination (3, 4). This qualitative study focuses on the challenges regarding the right to healthcare for children and adolescents with SCD and their families. The aims of this study were to (a) map the various perspectives and initiatives of SCD healthcare professionals, while focusing on existing best practices and lessons learned and (b) to provide practical recommendations relevant for high-income countries to improve accessibility of healthcare in SCD. Methods This qualitative study consisted of semi-structured, in-depth interviews which were conducted from February 1st to May 1st 2019 with SCD healthcare professionals, including (pediatric) hematologists, nurses, and psychosocial staff. Participants were affiliated with the SCORE (Sickle Cell Outcome REsearch) consortium which includes all SCD comprehensive care centers in the Netherlands (Fig 1). We identified eligible participants within SCORE and recruited participants using a combination of maximum variation and snowball sampling. Interviews occurred privately and were audio-recorded. The audio-recordings were transcribed verbatim and analyzed using the NVivoâ qualitative analysis software. Results Twenty-four healthcare professionals from different clinical sites participated in the study (Fig 1). Transcripts were coded into the four dimensions of health care access. Content analyses of the four dimensions in turn, revealed seven themes associated with best practices on topics related to improving accessibility of health care for children and adolescent SCD patients and their families (Fig 2). These themes included: 1) Cutting invisible costs: addressing the financial burden of a child with SCD; 2) Same-day appointments: reducing the amount of hospital visits; 3) Specialized and shared care: bridging the gap; 4) Optimizing methods of verbal and written communication: enabling mutual understanding between patients and healthcare professionals; 5) Building strong digital connections: improving the use of e-health while watching out for pitfalls; 6) Tools for patient empowerment and resilience: being aware of (self) stigmatization; and 7) Changing society: towards compassion and public awareness. Discussion The United Nations Convention on The Rights of the Child is the most widely signed and ratified human rights treaty and safeguards the right of the child to the enjoyment of the highest attainable standard of health. This right must be interpreted broadly, paying attention to all factors that may affect the realization of this right (5). Equity of access to healthcare for all patient populations requires the appreciation of intersecting vulnerabilities. This qualitative study provides best practices and solution-based recommendations from a grassroots-level to improve access to healthcare for children and adolescents with SCD and their families. Healthcare professionals experience a unique combination of intersecting vulnerabilities that characterize SCD patients and hampers their overall access to necessary healthcare. The seven key recommendations address these obstacles across all four dimensions of accessibility. Holistic implementation would positively impact the access to the highest attainable standard of healthcare for pediatric SCD patients and their families. These recommendations are built on local best practices that deserve wider implementation. They are especially relevant in the organization of SCD care, but all physicians will recognize these experiences with regard to healthcare in vulnerable patient populations in general. Disclosures Cnossen: Pfizer: Other: Travel Grants, Research Funding; Bayer: Other: Travel Grants, Research Funding; Novo Nordisk: Research Funding; Nordic Pharma: Research Funding; CSL Behring: Other: Travel Grants, Research Funding; Sobi: Research Funding; Baxter: Other: Travel Grants, Research Funding; Shire: Other: Travel Grants, Research Funding; Takeda: Other: Travel Grants, Research Funding; Roche: Other: Travel Grants; NWO: Other: Governmental grants , ZonMW, Innovation fund and Nationale Wetenschapsagenda 2018.

Raman tweezers have been used to study single blood cells in vivo without requiring invasive procedures. In the present study, we use optical tweezers to capture single blood cells (RBCs) in the microvessel of a mouse ear. Without the use of any invasive procedures, we were able to obtain the Raman spectra of single red blood cells from a mouse ear. An analysis of these spectra indicated that RBCs in arterioles are oxygenated, while those in the capillaries of venules are deoxygenated, those in vitro are similar to that in venules. In addition, hemoglobin in vivo was observed to be more concentrated than that in vitro. By studying the change of the band at 1604 cm−1, we concluded that the pH in arterioles is higher than that in venules. The information gained from the single RBCs in vivo is important for the understanding of the reaction of RBCs to changes in their environment and may have many applications in the diagnosis and treatment of red blood cell disorders.

The recent report by Kurtul et al on ‘‘Red Cell Distribution Width (RDW) and Contrast-Induced Nephropathy (CIN)’’ is very interesting. A similar finding that RDW could be predictive for CIN was also reported by Akkoyun et al. There are some concerns regarding using RDW. First, RDW is a red blood cell parameter derived from automated hematology analyzers. The results from different measurement techniques can vary and Kurtul et al did not mention this limitation. Furthermore, fragmented red cells can influence RDW values. In addition to coronary heart problems, several conditions can also result in increased fragmented red cells. In an area with a high prevalence of inherited red blood cell disorders, especially thalassemia, a high RDW value is common despite the absence of cardiac problems. Due to the possible problem with RDW, some newer parameters such as RDWstandard deviation and RDW coefficient of variation should be considered for use instead.

BACKGROUND: Sickle cell disease (SCD) describes a group of inherited red blood cell disorders. People with SCD have abnormal haemoglobin (Hb), called Hb S. In all forms of SCD, at least one of the two abnormal genes causes a person's body to make Hb S. In countries with limited resources, diagnostic technique should be simple and easy to perform with high sensitivity and specificity. METHODS: This study compared the paperbased sickle cell test and sodium metabisulfite sickling test using Hb electrophoresis as a gold standard. It was a crosssectional hospitalbased study which was conducted from July to October 2017 involving a total of 140 blood samples of under 10 years children presumed to have SCD. Blood samples in ethylenediaminetetraacetic acid anticoagulantcontaining vacutainers were used for SCD diagnosis by using paperbased and sodium metabisulfite sickling tests then confirmed by Hb electrophoresis as the gold standard. RESULTS: Blood specimens were from individuals aged 4 years ranged from 2 to 9 years. Slightly majority of blood specimens belonged to males, 54.3% (76/140) while the majority was from inpatients, 82.9% (116/140). Paperbased sickle cell test identified 46/140 (32.9%) Hb AA, 81/140 (57.9%) Hb, and 6/140 (4.3%) Hb AS. Sickling test identified 50/140 (35.7%) Hb AA and 87/140 (62.1%) Hb SS. Hb electrophoresis identified 50/140 (35.7%) Hb AA, 83/140 (59.3%) Hb SS, and 7/140 (5%) Hb AS. The paperbased sickle cell test had a sensitivity of 97.8% and specificity of 96.7% while the sickling test had the sensitivity of 96.7% and specificity of 100%. CONCLUSION: Paperbased sickle cell test was able to detect sickle cell carriers, Hb AS and shown high sensitivity and specificity; therefore, it can be used as a substitute for sickling test in countries with limited resource. However, paperbased sickle test is suitable for adults' population.

"Common red blood cell disorders encountered in the normal newborn nursery include hemolytic disease of the newborn and resultant hyperbilirubinemia, anemia, and polycythemia. A less frequent clinically relevant hematologic issue in newborns to be covered herein is thrombocytopenia."

The haemoglobinopathies are a complex group of red blood cell disorders. The ethnic diversity of the population in many parts of the UK means that these disorders are increasingly being seen in the antenatal setting. With the planned introduction of both antenatal and newborn screening programmes for haemoglobinopathies in England and Wales, a review of the subject is timely. This article explains the genetic background and clinical features of the major haemoglobinopathies, discusses antenatal screening and prenatal diagnosis, and highlights the implications of pregnancy for women with these disorders.

A vast excess of α-globin production and inadequate γ-globin compensation lead to the development of severe anemia in human β-thalassemia. Newly identified modifiers of α- and γ-globin synthesis and insights into the mechanisms of globin regulation provide the tools for potential new approaches to treating this and other red blood cell disorders. In the study by Han and colleagues in this issue of the JCI, the activity of a heme-regulated protein, HRI, is shown to modulate the accumulation of excess α-globin chains in murine β-thalassemia and to decrease the severity of the disease.

PubMedID: 24376176 Background: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC)

Hereditary disorders of erythrocytes are common in many areas of the world, including the Middle East. In some regions of the Middle East more than 10% of the population are carriers of a gene for one of these conditions. When patients from the Middle East seek medical care in the West, an unrecognized but clinically important erythrocyte disorder can result in serious complications during routine medical care, such as a drug-induced hemolytic crisis. This article reviews the most important and most common inherited red blood cell disorders in Middle Eastern patients, including glucose-6-phosphate dehydrogenase deficiency, the thalassemias, and sickle cell disorders. We discuss when to suspect such conditions, how to determine their presence, and how to avoid potential complications related to them. Although a detailed discussion of treatment of erythrocyte disorders is beyond the scope of this article, some general management principles are described.

The congenital dyserythropoietic anemias (CDAs) are inherited red blood cell disorders representing ineffective erythropoiesis and dyserythropoietic changes in the bone marrow. We recently diagnosed a female patient with undiagnosed congenital anemia as type IV CDA caused by a heterozygous missense mutation of the erythroid-specific transcription factor, KLF1; c.973G>A, p. E325K. Although the mutation has been reported in a male patient characterized as hydrops fetalis, severe neonatal jaundice and transfusion-dependent anemia (Arnaud L et al., Am J Hum Genet, 2010), the proband showed relatively mild phenotype showing moderate dyserythropoietic anemia. In order to investigate the pathological significance of mutant KLF1 during erythroid cell development and differentiation, we generated induced pluripotent stem cells (iPSCs) from peripheral blood of the CDA patient (CDA-iPSCs), and utilized these cells to establish in vitro CDA model for better understanding of its molecular basis. CDA-iPSCs were generated from T lymphocytes in peripheral blood mononuclear cells. Hematopoietic precursors were induced from CDA-iPSCs by embryoid bodies formation. CD34(+) precursor cells were isolated and further cultured in liquid culture with cytokine cocktail (erythropoietin (EPO), interleukin (IL)-3, and stem cell factor (SCF)) for additional 1-3 weeks. Flow cytometric analysis showed that CDA-iPSC-derived cells contained significantly lower percentage of CD235a(+)/CD71(+) erythroid lineage cells than the cells derived from control iPSCs, and lack expression of the adhesion molecule CD44, which is known to be down regulated in peripheral blood erythroid cells of CDA patients (Arnaud L et al., Am J Hum Genet, 2010). In addition, colony-forming unit (CFU) assay indicated that CD34(+) fraction derived from CDA-iPSCs contained a lower number of erythroid colony-forming cells and the most of the cells in these colonies are morphologically abnormal, in comparison with control iPSCs. We next evaluated mRNA expression levels of fetal (HBG1 and HBG2), embryonic (HBE), and adult (HBB) globins, resulting that HBG1 and HBG2 were significantly increased in CDA-iPSCs-derived erythroid lineage cells, whereas HBE showed no significant change and HBB was decreased in CDA-iPSCs-derived erythroid lineage cells. However, BCL11A, one of the target genes of KLF1 and also known as a suppressor of HBG1 and HBG2, was not decreased in the presence KLF1 gene mutation, indicating that elevated HBG1 and HBG2 in CDA-iPSCs-derived erythroid cells was mediated by other mechanism like Leukemia/lymphoma Related Factor (LRF; Masuda T et al., Science, 2016). Here we suggest that our model provides insights on understanding the mechanisms of type IV CDA and the effect of KLF1 gene mutation on clinical phenotype and it would be a useful tool for drug screening and identification of novel biomarker for the rare congenital anemia. Figure 1 Induction of erythroid differentiation from human iPSCs Figure 2 Flow cytometric analysis of erythroid cells induced from CDA-iPSCs Figure 3 RT-PCR analysis of erythroid cells induced from CDA-iPSCs Disclosures Kohara: SBI Pharmaceuticals: Research Funding. Miyamoto:SBI Pharmaceuticals: Research Funding. Tani:Oncolys BioPharma: Equity Ownership; SymBio Pharmaceuticals: Consultancy, Equity Ownership; SBI Pharmaceuticals: Research Funding; Shinnihonseiyaku: Research Funding.

Human red blood cells exist to facilitate exchange of respiratory gases between the lungs and the tissues of the body. The article is a «biographical sketch» of red blood cells, describing how their structure, chemistry and activities are geared to serve this purpose. In the process, the cause of some red blood cell disorders has been explained in a simplified manner.

This chapter focuses on genetic diseases that are expressed primarily as disorders of the red blood cell (RBC), although leukocytes and platelets also can be affected. Some of these conditions cause hemolytic anemia (enzyme and membrane disorders), some are associated with impaired RBC production (hypoplastic, megaloblastic, sideroblastic, and dyserythropoietic anemias) and some, although not associated with anemia, cause clinical problems due to abnormal erythrocyte function (methemoglobinemia).

Hematopoietic stem cell transplantation remains the only curative therapy for certain genetic diseases of the hematopoietic system, including some inheritable deficiencies in red blood cells (RBC). Recent advances in induced pluripotent stem cells may open a new era for the cure of such severe genetic RBC diseases.