Considerations for the development of iPSC-derived cell therapies: a review of key challenges by the JSRM-ISCT iPSC Committee.

Since their first production in 2007, human induced pluripotent stem cells (iPSCs) have provided a novel platform for the development of various cell therapies targeting a spectrum of diseases, ranging from rare genetic eye disorders to cancer treatment. However, several challenges must be tackled for iPSC-based cell therapy to enter the market and achieve broader global adoption. This white paper, authored by the Japanese Society for Regenerative Medicine (JSRM) - International Society for Cell Therapy (ISCT) iPSC Committee delves into the hurdles encountered in the pursuit of safe and economically viable iPSC-based therapies, particularly from the standpoint of the cell therapy industry. It discusses differences in global guidelines and regulatory frameworks, outlines a series of quality control tests required to ensure the safety of the cell therapy, and provides details and important considerations around cost of goods (COGs), including the impact of automated advanced manufacturing.

E-learning in transfusion medicine: An exploratory qualitative assessment.

BACKGROUND AND OBJECTIVES: E-learning programmes are increasingly offered in transfusion medicine (TM) education. The aim of this study was to explore facilitators and barriers to TM e-learning programmes, including assessment of learning outcomes and measures of effectiveness. MATERIALS AND METHODS: Participants selected from a prior survey and representing a diverse number of international e-learning programmes were invited to participate. A mixed methodology was employed, combining a survey and individual semi-structured one-on-one interviews. Interview data were analysed inductively to explore programme development, evaluation, and facilitators and barriers to implementation. RESULTS: Fourteen participants representing 13 institutions participated in the survey and 10 were interviewed. The e-learning programmes have been in use for a variable duration between 5 and 16 years. Funding sources varied, including government and institutional support. Learner assessment methods varied and encompassed multiple-choice-questions (n = 12), direct observation (n = 4) and competency assessment (n = 4). Most regional and national blood collection agencies rely on user feedback and short-term learning assessments to evaluate their programmes. Only one respondent indicated an attempt to correlate e-learning with clinical practices. Factors that facilitated programme implementation included support from management and external audits to ensure compliance with regulatory educational and training requirements. Barriers to programme implementation included the allocation of staff time for in-house development, enforcing compliance, keeping educational content up-to-date and gaining access to outcome data for educational providers. CONCLUSION: There is evidence of considerable diversity in the evaluation of e-learning programmes. Further work is needed to understand the ultimate impact of TM e-learning on transfusion practices and patient outcomes.

A machine-learning model that incorporates CD45 surface expression predicts hematopoietic progenitor cell recovery after freeze-thaw.

BACKGROUND AIMS: Sufficient doses of viable CD34+ (vCD34) hematopoietic progenitor cells (HPCs) are crucial for engraftment. Additional-day apheresis collections can compensate for potential loss during cryopreservation but incur high cost and additional risk. To aid predicting such losses for clinical decision support, we developed a machine-learning model using variables obtainable on the day of collection. METHODS: In total, 370 consecutive autologous HPCs, apheresis-collected since 2014 at the Children's Hospital of Philadelphia, were retrospectively reviewed. Flow cytometry was used to assess vCD34% on fresh products and thawed quality control vials. The ratio of vCD34% thawed to fresh, which we call "post-thaw index," was used as an outcome measure, with a "poor" post-thaw index defined as <70%. HPC CD45 normalized mean fluorescence intensity (MFI) was calculated by dividing CD45 MFI of HPCs to the CD45 MFI of lymphocytes in the same sample. We trained XGBoost, k-nearest neighbor and random forest models for the prediction and calibrated the best model to minimize falsely-reassuring predictions. RESULTS: In total, 63 of 370 (17%) products had a poor post-thaw index. The best model was XGBoost, with an area under the receiver operator curve of 0.83 evaluated on an independent test data set. The most important predictor for a poor post-thaw index was the HPC CD45 normalized MFI. Transplants after 2015, based on the lower of the two vCD34% values, showed faster engraftment than older transplants, which were based on fresh vCD34% only (average 10.6 vs 11.7 days, P = 0.0006). CONCLUSIONS: Transplants taking into account post-thaw vCD34% improved engraftment time in our patients; however, it came at the cost of unnecessary multi-day collections. The results from applying our predictive algorithm retrospectively to our data suggest that more than one-third of additional-day collections could have been avoided. Our investigation also identified CD45 nMFI as a novel marker for assessing HPC health post-thaw.

COVID-19 and the impact on blood availability and transfusion practices in low- and middle-income countries.

BACKGROUND/CASE STUDIES: The coronavirus disease 2019 (COVID-19) pandemic disrupted the global blood supply. Low- and middle-income countries (LMICs) already experienced blood supply deficits that preceded the pandemic. We sought to characterize the challenges experienced during the pandemic, and adaptations, such as COVID-19 convalescent plasma (CCP). STUDY DESIGN/METHODS: A cross-sectional survey explored blood availability, challenges, and adaptations. The survey contained 31 questions, e-mailed in English, French, or Spanish, to selected LMIC blood transfusion practitioners. Data acquisition occurred between October 28 and December 28, 2020. A mixed methods analysis followed. RESULTS/FINDINGS: A total of 31 responses from 111 invitations represented 26 LMIC countries. Languages included English (22, 71%), Spanish (7, 22.6%), and French (2, 6.4%). Most respondents (29/31, 93.5%) collected blood; 58% also transfused blood (18/31). The supply of blood came from hospital-based blood donations (61%, 11/18); blood suppliers (17%, 3/18); and both sources (22%, 4/18). Collectively, 77.4% (24/31) of respondents experienced a decline in blood availability, ranging from 10% to 50%. Contributing factors included public fear of COVID-19 (21/24); stay-at-home measures (18/24); logistics (14/24); and canceled blood drives (16/24). Adaptations included increased collaboration within and between institutions (17/27), donor eligibility changes (21/31); social media or phone promotion (22/39); and replacement donation (3/27). Fifteen of 31 responses reported CCP donation (48.4%); CCP transfusion occurred in 6 (19.4%). The primary barrier was engaging recovered patients for donation (7/15). CONCLUSION: Our survey describes challenges experienced by LMIC blood systems during the COVID-19 pandemic. While the decline in blood supplies was severe, adaptive measures included collaboration, outreach, and CCP programs.

Psychological impact of the COVID-19 pandemic on young professionals in blood banks and transfusion services: A global cross-sectional survey.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic brought about changes to daily life as measures to contain the spread of the virus increased across the world. The aim of this survey was to assess the psychological impact of the pandemic on young professionals (YPs) in transfusion medicine. MATERIALS AND METHODS: A cross-sectional web-based survey was distributed electronically to ISBT members inviting YPs (≤40 years) to participate. Statistical analysis was performed using SPSS software. RESULTS: Two hundred and fifty-nine YPs completed the survey, including 107 clinicians/physicians and/or nurses. Almost half of the YPs (52.5%) indicated increased stress levels and 15.4% indicated symptoms of depression. YPs highlighted the loss of social engagement (59.1%) and increased pressure from information seen on media (35.5%) as factors negatively impacting their psychological wellbeing. Further, 20.8% expressed increased economic stress resulting from concerns about job security. Almost half of the YPs indicated that their organization provided moderate/occasional holistic support to them and their families. Sixty percent and 74.4% of YPs reported increased workload and staff absence due to COVID-19 infection, respectively. Only half of clinicians/physicians and/or nurses indicated that they often had sufficient personal protective equipment. The majority of these (76.6%) had family/household members living with them, and 61% indicated that they were significantly worried about infecting them because of the nature of their work. CONCLUSION: COVID-19 had a major impact on the well-being of YPs working in transfusion medicine. Measures are required to ensure that YPs are protected and mentally supported while undertaking their duties in current and future pandemics.

Management of blood transfusion services in low-resource countries.

BACKGROUND AND OBJECTIVES: Enabling universal access to safe blood components should be a key component of every country's national healthcare strategy. This study aimed to assess the current status of infrastructure and resources of blood transfusion services (BTS) in low- and middle-income countries. MATERIALS AND METHODS: A cross-sectional survey was designed to gather information on blood donations, components, redistribution, testing resources and quality management systems (QMSs). The survey was distributed to the International Society of Blood Transfusion members between October 2021 and November 2021. RESULTS: A total of 54 respondents from 20 countries responded to the survey. This included hospital-based BTS/blood centres (46%), national blood centres (11%)and national and regional blood services (11%). Voluntary non-remunerated, replacement and paid donors accounted for 94.2%, 84.6% and 21.1% of donations, respectively. Apheresis donation was available in 59.6% of institutions. National/regional criteria for redistribution of blood components were reported by 75.9% of respondents. Blood components incurred payment charges in 81.5% of respondents' institutions, and payments were borne by patients in 50% of them. Testing methods, such as manual (83%), semi-automated (68%) or fully automated (36.2%), were used either alone or in combination. QMSs were reported in 17 institutions, while accreditation and haemovigilance were reported in 12 and 8 countries, respectively. CONCLUSION: QMS was implemented in most of the countries despite the common use of paid donations and the lack of advanced testing. Efforts to overcome persistent challenges and wider implementation of patient blood management programmes are required.

Molecular blood group screening in Omani blood donors.

BACKGROUND AND OBJECTIVES: Blood group genotyping has been used in different populations. This study aims at evaluating the genotypes of common blood group antigens in the Omani blood donors and to assess the concordance rate with obtained phenotypes. MATERIAL AND METHODS: Blood samples from 180 Omani donors were evaluated. Samples were typed by serological methods for the five blood group systems MNS, RH (RHD/RHCE), KEL, FY and JK. Samples were genotyped using RBC-FluoGene vERYfy eXtend kit (inno-train©). Predicted phenotypic variants for 70 red blood cell antigens among the MNS, RH (RHD/RHCE), KEL, FY, JK, DO, LU, YT, DI, VEL, CO and KN blood group systems were assessed. RESULTS: Simultaneous phenotype and genotype results were available in 130 subjects. Concordance rate was >95% in all blood group systems with exception of Fy(b+) (87%). Homozygous GATA-1 mutation leading to erythroid silencing FY*02N.01 (resulting in the Fy(b-)ES phenotype) was detected in 81/112 (72%) of genotyped samples. In addition, discrepant Fyb phenotype/genotype result was obtained in 14/112 samples; 13 of which has a heterozygous GATA-1 mutation and one sample with a wild GATA genotype. D and partial e c.733C>G variants expressing the V+VS+ phenotype were found in 22/121 (18.2%) and 14/120 (11.7%) of the samples, respectively. Di(a-b+), Js(a-b+), Yt(a+b-) and Kn(a+b-) genotype frequencies were 99.4%, 95.8%, 91.9% and 97.7%, respectively. CONCLUSION: In conclusion, we report a high frequency of FY*02N.01 allele due to homozygous c.-67T>C GATA-1 single-nucleotide variation. This is the first study reporting the detailed distribution of common and rare red cell genotypes in Omani blood donors.

Early and out-of-hospital use of COVID-19 convalescent plasma: An international assessment of utilization and feasibility.

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.

International Society of Blood Transfusion survey of experiences of blood banks and transfusion services during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has impacted blood systems worldwide. Challenges included maintaining blood supplies and initiating the collection and use of COVID-19 convalescent plasma (CCP). Sharing information on the challenges can help improve blood collection and utilization. MATERIALS AND METHODS: A survey questionnaire was distributed to International Society of Blood Transfusion members in 95 countries. We recorded respondents' demographic information, impacts on the blood supply, CCP collection and use, transfusion demands and operational challenges. RESULTS: Eighty-two responses from 42 countries, including 24 low- and middle-income countries, were analysed. Participants worked in national (26.8%) and regional (26.8%) blood establishments and hospital-based (42.7%) institutions. CCP collection and transfusion were reported by 63% and 36.6% of respondents, respectively. Decreases in blood donations occurred in 70.6% of collecting facilities. Despite safety measures and recruitment strategies, donor fear and refusal of institutions to host blood drives were major contributing factors. Almost half of respondents working at transfusion medicine services were from large hospitals with over 10,000 red cell transfusions per year, and 76.8% of those hospitals experienced blood shortages. Practices varied in accepting donors for blood or CCP donations after a history of COVID-19 infection, CCP transfusion, or vaccination. Operational challenges included loss of staff, increased workloads and delays in reagent supplies. Almost half of the institutions modified their disaster plans during the pandemic. CONCLUSION: The challenges faced by blood systems during the COVID-19 pandemic highlight the need for guidance, harmonization, and strengthening of the preparedness and the capacity of blood systems against future infectious threats.

E-learning/online education in transfusion medicine: A cross-sectional international survey.

OBJECTIVES: This survey aims to assess the scope of transfusion e-learning courses in blood establishments and transfusion services internationally. BACKGROUND: E-learning/online education is increasingly used in the education of medical professionals. There is limited published data on the use of e-learning for transfusion medicine. MATERIAL AND METHODS: An International survey was designed and distributed to all members of the International Society of Blood Transfusion to assess utilisation of e-learning in their institutions. Descriptive statistics were used to summarise the results. RESULTS: A total of 177 respondents participated, 68 of which had e-learning modules in their institutions. Approximately two-thirds of the courses were developed in-house (66%), and 63% are available to learners from outside the host institutions. In one-third of institutions, these courses were established during the COVID-19 pandemic, while 15% had used e-learning courses for more than 10 years. The courses target different audiences and topics ranging from blood donation to hemovigilance. The most common audiences were physicians (71%), laboratory scientists/technologists (69%) and transfusion practitioners (63%). Formal assessment of learning outcomes is used in 70% of the programs. CONCLUSIONS: The survey demonstrates the widespread use of e-learning courses in transfusion education, with a substantial proportion being developed during the COVID-19 pandemic.

Quality of evidence-based guidelines for platelet transfusion and use: A systematic review.

BACKGROUND: Guidelines for platelet (PLT) transfusion are an important source of information for clinicians. Although guidelines intend to increase consistency and quality of care, variation in methodology and recommendations may exist that could impact the value of a guideline. We aimed to determine the quality of existing PLT transfusion guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument and to describe the inconsistencies in recommendations. STUDY DESIGN AND METHODS: A systematic search was undertaken for evidence-based guidelines from January 1, 2013, to January 25, 2019. Citations were reviewed in duplicate for inclusion and descriptive data extracted. Four physicians appraised the guideline using the AGREE II instrument and the scaled score for each item evaluated was calculated. The protocol was registered in PROSPERO. RESULTS: Of 6744 citations, 6740 records were screened. Seven of 28 full-text studies met the inclusion criteria. The median scaled score (and the interquartile range of the scaled score) for the following items were as follows: scope and purpose, 94% (8%); stakeholder involvement, 63% (18%); rigor of development, 83% (14%); clarity of presentation, 94% (6%); applicability, 58% (20%); and editorial independence, 77% (4%). Overall quality ranged from 4 to 7 (7 is the maximum score). Inconsistent recommendations were on prophylactic PLT transfusion in hypoproliferative thrombocytopenia in the presence of risk factors and dose recommendations. CONCLUSION: Inconsistencies between guidelines and variable quality highlight areas for future guideline writers to address. Areas of specific attention include issues of stakeholder involvement and applicability.

Transfusion medicine and blood banking education and training for blood establishment laboratory staff: A review of selected countries in Africa.

BACKGROUND: Avoidable human error is a significant cause of transfusion adverse events. Adequately trained, laboratory staff in blood establishments and blood banks, collectively blood facilities, are key in ensuring high-quality transfusion medicine (TM) services. Gaps in TM education and training of laboratory staff exist in most African countries. We assessed the status of the training and education of laboratory staff working in blood facilities in Africa. STUDY DESIGN AND METHODS: A cross-sectional study using a self-administered pilot-tested questionnaire was performed. The questionnaire comprised 26 questions targeting six themes. Blood facilities from 16 countries were invited to participate. Individually completed questionnaires were grouped by country and descriptive analysis performed. RESULTS: Ten blood establishments and two blood banks from eight African countries confirmed the availability of a host of training programs for laboratory staff; the majority of which were syllabus or curriculum-guided and focused on both theoretical and practical laboratory skills development. Training was usually preplanned, dependent on student and trainer availability and delivered through lecture-based classroom training as well as formal and informal on the job training. There were minimal online didactic and self-directed learning. Teaching of humanistic values appeared to be lacking. CONCLUSION: We confirmed the availability of diverse training programs across a variety of African countries. Incorporation of virtual learning platforms, rather than complete reliance on didactic, in-person training programs may improve the education reach of the existing programs. Digitalization driven by the coronavirus disease 2019 pandemic may provide an opportunity to narrow the knowledge gap in low- and middle-income countries (LMICs).

Global survey of transfusion medicine curricula in medical schools: Challenges and opportunities.

BACKGROUND: Physician's knowledge in transfusion medicine (TM) is critical for patient safety. Therefore, ensuring that medical schools provide adequate education in TM is important. The aim of this study was to assess the status of TM education at a global level. STUDY DESIGN AND METHODS: A comprehensive anonymous survey to assess TM education in existing medical school curricula was developed. The survey was distributed to deans and educational leads of medical schools in a range of low-, medium-, high-, and very high-human development index (HDI) countries. It included 20 questions designed to assess specific domains including structure of TM curriculum and teaching faculty. RESULTS: The response rate was 53%. The majority of responding schools from very-high-HDI countries offered a 6-year curriculum after high school or a 4-year curriculum after college education, whereas most schools from medium-HDI countries offered a 5-year medical curriculum. A formal teaching program was available in only 42% of these schools in contrast to 94% of medical schools from very high-HDI. Overall, 25% of all medical schools did not offer structured TM teaching. When offered, most TM teaching was mandatory (95%) and integrated within the third and fourth year of medical school. Formal assessment of TM knowledge was done in 72% of all responding medical schools. More than half of the deans considered the TM education in their medical schools as inadequate. CONCLUSION: Despite its limitations, the current survey highlights significant gaps and opportunities of TM education at a global scale.

Clinical use of Convalescent Plasma in the COVID-19 pandemic: a transfusion-focussed gap analysis with recommendations for future research priorities.

BACKGROUND AND OBJECTIVES: Use of convalescent plasma for coronavirus disease 2019 (COVID-19) treatment has gained interest worldwide. However, there is lack of evidence on its dosing, safety and effectiveness. Until data from clinical studies are available to provide solid evidence for worldwide applicable guidelines, there is a need to provide guidance to the transfusion community and researchers on this emergent therapeutic option. This paper aims to identify existing key gaps in current knowledge in the clinical application of COVID-19 convalescent plasma (CCP). MATERIALS AND METHODS: The International Society of Blood Transfusion (ISBT) initiated a multidisciplinary working group with worldwide representation from all six continents with the aim of reviewing existing practices on CCP use from donor, product and patient perspectives. A subgroup of clinical transfusion professionals was formed to draft a document for CCP clinical application to identify the gaps in knowledge in existing literature. RESULTS: Gaps in knowledge were identified in the following main domains: study design, patient eligibility, CCP dose, frequency and timing of CCP administration, parameters to assess response to CCP treatment and long-term outcome, adverse events and CCP application in less-resourced countries as well as in paediatrics and neonates. CONCLUSION: This paper outlines a framework of gaps in the knowledge of clinical deployment of CPP that were identified as being most relevant. Studies to address the identified gaps are required to provide better evidence on the effectiveness and safety of CCP use.

Guidance for the procurement of COVID-19 convalescent plasma: differences between high- and low-middle-income countries.

BACKGROUND AND OBJECTIVES: COVID-19 convalescent plasma (CCP) has been used, predominantly in high-income countries (HICs) to treat COVID-19; available data suggest the safety and efficacy of use. We sought to develop guidance for procurement and use of CCP, particularly in low- and middle-income countries (LMICs) for which data are lacking. MATERIALS AND METHODS: A multidisciplinary, geographically representative group of individuals with expertise spanning transfusion medicine, infectious diseases and haematology was tasked with the development of a guidance document for CCP, drawing on expert opinion, survey of group members and review of available evidence. Three subgroups (i.e. donor, product and patient) were established based on self-identified expertise and interest. Here, the donor and product-related challenges are summarized and contrasted between HICs and LMICs with a view to guide related practices. RESULTS: The challenges to advance CCP therapy are different between HICs and LMICs. Early challenges in HICs related to recruitment and qualification of sufficient donors to meet the growing demand. Antibody testing also posed a specific obstacle given lack of standardization, variable performance of the assays in use and uncertain interpretation of results. In LMICs, an extant transfusion deficit, suboptimal models of donor recruitment (e.g. reliance on replacement and paid donors), limited laboratory capacity for pre-donation qualification and operational considerations could impede wide adoption. CONCLUSION: There has been wide-scale adoption of CCP in many HICs, which could increase if clinical trials show efficacy of use. By contrast, LMICs, having received little attention, require locally applicable strategies for adoption of CCP.

Lessons learned in the collection of convalescent plasma during the COVID-19 pandemic.

BACKGROUND: The lack of definitive treatment or preventative options for COVID-19 led many clinicians early on to consider convalescent plasma (CCP) as potentially therapeutic. Regulators, blood centres and hospitals worldwide worked quickly to get CCP to the bedside. Although response was admirable, several areas have been identified to help improve future pandemic management. MATERIALS AND METHODS: A multidisciplinary, multinational subgroup from the ISBT Working Group on COVID-19 was tasked with drafting a manuscript that describes the lessons learned pertaining to procurement and administration of CCP, derived from a comprehensive questionnaire within the subgroup. RESULTS: While each country's responses and preparedness for the pandemic varied, there were shared challenges, spanning supply chain disruptions, staffing, impact of social distancing on the collection of regular blood and CCP products, and the availability of screening and confirmatory SARS-CoV-2 testing for donors and patients. The lack of a general framework to organize data gathering across clinical trials and the desire to provide a potentially life-saving therapeutic through compassionate use hampered the collection of much-needed safety and outcome data worldwide. Communication across all stakeholders was identified as being central to reducing confusion. CONCLUSION: The need for flexibility and adaptability remains paramount when dealing with a pandemic. As the world approaches the first anniversary of the COVID-19 pandemic with rising rates worldwide and over 115 million cases and 2·55 million deaths, respectively, it is important to reflect on how to better prepare for future pandemics as we continue to combat the current one.

ABO blood group and COVID-19: a review on behalf of the ISBT COVID-19 Working Group.

Growing evidence suggests that ABO blood group may play a role in the immunopathogenesis of SARS-CoV-2 infection, with group O individuals less likely to test positive and group A conferring a higher susceptibility to infection and propensity to severe disease. The level of evidence supporting an association between ABO type and SARS-CoV-2/COVID-19 ranges from small observational studies, to genome-wide-association-analyses and country-level meta-regression analyses. ABO blood group antigens are oligosaccharides expressed on red cells and other tissues (notably endothelium). There are several hypotheses to explain the differences in SARS-CoV-2 infection by ABO type. For example, anti-A and/or anti-B antibodies (e.g. present in group O individuals) could bind to corresponding antigens on the viral envelope and contribute to viral neutralization, thereby preventing target cell infection. The SARS-CoV-2 virus and SARS-CoV spike (S) proteins may be bound by anti-A isoagglutinins (e.g. present in group O and group B individuals), which may block interactions between virus and angiotensin-converting-enzyme-2-receptor, thereby preventing entry into lung epithelial cells. ABO type-associated variations in angiotensin-converting enzyme-1 activity and levels of von Willebrand factor (VWF) and factor VIII could also influence adverse outcomes, notably in group A individuals who express high VWF levels. In conclusion, group O may be associated with a lower risk of SARS-CoV-2 infection and group A may be associated with a higher risk of SARS-CoV-2 infection along with severe disease. However, prospective and mechanistic studies are needed to verify several of the proposed associations. Based on the strength of available studies, there are insufficient data for guiding policy in this regard.

The impact of blood donation on blood counts and ferritin levels: A multi-center study from the Eastern Mediterranean region.

Regular donation of whole blood may lead to iron deficiency. In this study, we aimed to assess the impact of frequent whole blood donation on hematological parameters. Whole blood donors were enrolled from four blood banks located in Saudi Arabia, United Arab Emirates (UAE), Libya and Oman, between 2016 and 2017. SPSS version 21.0 was used to generate descriptive and inferential statistics. A total number of 3096 blood donors were screened (males 93.8 %, females; 6.2 %), with a mean donor age of 35.29 ± 9.31 years. For male blood donors, the majority (1073) had 1-3 previous donations. Increased frequency of donations was significantly associated with increases in age and weight, decreases in Hemoglobin (Hb) and ferritin measures, and increases in Red Blood Cells (RBC) counts. A General Linear Model (GLM) adjusted for age and weight indicated negative impacts on White Blood Cells (WBC) counts and ferritin. A weak correlation between the Hb and ferritin levels was observed (r = 0.160, P > 0.001). For female donors, the majority (63 out of 114) were first time donors. Increased frequency of donations was significantly associated with an increase in age and a decrease in HCT readings. A GLM adjusted for age and weight indicated a negative impact on ferritin. A strong correlation was observed between the Hb and ferritin levels for the most frequent female donors (r = 0.636, P > 0.001). In conclusion, regular whole blood donation impacts hematological parameters in particular the levels of ferritin in the serum.

α-Globin Genotypes Associated with Hb H Disease: A Report from Oman and a Review of the Literature from the Eastern Mediterranean Region.

α-Thalassemia (α-thal) is the most common autosomal recessive hemoglobinopathy. There is a vast diversity and geographical variability in underlying genotypes in Hb H (ß4) patients. Herein, we describe the genotypes found in the largest report of Omani Hb H patients. Moreover, we reviewed and summarized the literature published from the Eastern Mediterranean region. A retrospective review of all genetically confirmed Hb H disease patients diagnosed between 2007 and 2017 at Sultan Qaboos University Hospital, Muscat, Oman, was performed. Hematological parameters and clinical presentations were assessed. Both α-globin genes were screened for deletional and nondeletional mutations using a stepwise diagnostic strategy as described before. A total of 52 patients (27 females and 25 males) with a mean age of 20.6 years (range 0.23-80.0) were molecularly confirmed to carry Hb H disease. The patients had a hemoglobin (Hb) level of 9.3 g/dL (range 5.7-13.0) and mean corpuscular volume (MCV) of 58.4 fL (range 48.2-82.1). A total of eight genotype combinations were identified, with α2 polyadenylation signal mutation (polyA1) (AATAAA>AATAAG (αPA1α/αPA1α), often cited as αT-Saudiα/αT-Saudiα, being the most common (53.8%) followed by -α3.7/- -MED I (28.8%). Our cohort also included patients with combinations of αPA1 with other Hb variants: αPA1α/αPA1α with Hb S (HBB: c.20A>T) trait (n = 2), -α3.7/αPA1α (n = 2) and αcodon 19α (HBA2: c.56delG)/αPA1α (n = 1). Nondeletional Hb H disease due to the αPA1 mutation is the most common in Omanis. Molecular diagnosis is necessary for accurate confirmation of the diagnosis of α-thal, determination of underlying genotypes, follow-up and counseling.

Red cell alloimmunization in transfusion-dependent and transfusion-independent beta thalassemia: A review from the Eastern Mediterranean Region (EMRO).

BACKGROUND: ß-Thalassemia is considered one of the common hemoglobin disorders in the Arabian Peninsula. Red blood cell (RBC) transfusion is a crucial component of the management of transfusion-dependent ß-Thalassemia patients. Patients with Thalassemia Intermedia (TI), also known as non-transfusion dependent ß-thalassemia, have a wide clinical presentation and variable transfusion dependence. Rates of RBC alloimmunization and its risk factors in transfusion-dependent ß-thalassemia patients varied between different reports. Risk of alloimmunization is higher in TI patients. MATERIAL AND METHODS: A literature review on existing reports on alloimmunization rates and risk factors in transfusion dependent and non-transfusion dependent ß-thalassemia in the Eastern Mediterranean region was performed. RESULTS: A total of 17 publications were found. Reported rates of alloimmunization among transfusion-dependent ß-Thalassemia patients ranged between 2.87 and 30 % and between 6.8 and 19.5 % among TI patients. Most centers utilize ABO and RhD matched RBCs. The most common antibodies described are anti-K and anti-E. The risk factors described included age at onset of transfusion, gender, history of splenectomy, duration of transfusion and number of units transfused. Rate of autoantibody formation ranged between 0.1 and 45 %. CONCLUSION: Our review showed variable alloimmunization rates and risk factors in thalassemia patients and scant data on TI patients. The commonest antibodies are anti-K and anti-E. Further studies are required in addressing the rate of alloimmunization, cross-match requirements and role of genotyping in this group of patients. Transfusion support of patients with thalassemia necessitates the availability of blood bank facilities and specialized expertise.