Survey-based assessment of hematopoietic stem cell graft manipulation (minimal) by cell therapy labs supporting hematopoietic stem cell transplants in India.

BACKGROUND AIMS: Hematopoietic stem cell transplants (HSCTs) are increasingly being offered to patients in India for various conditions. The Indian Stem Cell Transplant Registry shows that a total of 2533 transplants were done in India in 2019. METHODS: An epidemiological descriptive cross-sectional survey (55 questions) of centers providing HSCT in India was planned to analyze variations in policies and practices regarding HSCT graft manipulation (i.e., plasma reduction, red blood cell [RBC] depletion and cryopreservation). A total of 63 of 102 centers responded to the survey (response rate, 61.7%), mostly from the northern part of India (27 of 63 [42.8%]). RESULTS: The majority of responding centers reported performing >50 HSCTs annually (n = 24 [38%]), and 92% (58 of 63) performed stem cell collections from a pediatric donor/patient (age <18 years). A total of 56 of 63 responding centers indicated that they did product manipulations involving cryopreservation (n = 45), plasma reduction (n = 42) and RBC depletion (n = 28). Cryopreservation was primarily done by blood centers (27 of 45 [60%]), with dimethyl sulfoxide (DMSO) being the primary constituent, used most commonly at a concentration of 5-10% (28 of 45 centers). Dump freezing was most commonly used (27 of 45) with a -80°C deep freezer. A 7-aminoactinomycin D based viability assessment was also most commonly used (30 of 45). Thawing of the product was done mainly at the bedside (30 of 45) using a wet-type thawer (36 of 45), and washing of DMSO was done by a few centers (seven of 45). Plasma reduction and RBC depletion were primarily done for ABO incompatibility at blood centers. CONCLUSIONS: This survey demonstrates the lack of standardization and uniformity in the minimal manipulation of hematopoietic stem cell grafts in centers supporting HSCT in India. This work also highlights the need for more studies and country-specific recommendations to establish best practices.

Knowledge assessment of a donor adverse reaction severity grading tool by the National Blood Donor Vigilance Programme of India.

BACKGROUND AND OBJECTIVES: The severity grading tool (SGT) was recently designed by the Association for Advancement of Blood and Biotherapies (AABB) to have more objectivity in severity assignment for an adverse donor reaction after blood donation. A study was performed in India to assess the knowledge (post-training) and determine the degree of agreement of the SGT between participating centres and the subject expert group. MATERIALS AND METHODS: This prospective cross-sectional survey-based study was conducted by the National Coordinating Centre (NCC) of the National Blood Donor Vigilance Programme (NBDVP) of India. Thirty-five real-world case scenarios, validated by seven national and two international experts, were sent to the participating centres, and their responses received (diagnosis and severity grade) were compared and analysed. RESULTS: A total of 50 blood centres participated in the study. The overall agreement between the participating centres and the expert group was 66.4%, with a fair Kendall's coefficient of concordance (W) of 0.271 (p-value < 0.05). The degree of agreement was observed to be more than 80% for 12 centres, 60%-80% for 27 centres and <60% for 11 centres. The overall degree/percentage of agreement for cases with single and multiple types of donor adverse reaction was 71.3% and 42.6%, respectively. CONCLUSION: The SGT will be an efficient mode to have uniform objective reporting of the adverse donor reactions and may be implemented in the NBDVP of India. This study also highlights the need for training of the blood centres on the basic definitions and categorization of the donor's adverse reaction.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Patient blood management in adults and children: What have we achieved, and what still needs to be addressed?

An overview of Patient Blood Management (PBM), with its main scope to preserve the patient's own blood to improve the patient's outcome, is presented here, including the research gaps that needs to be addressed, particularly in the pediatric age group. Next, novel techniques to analyse PBM data and the challenges and strategies of PBM implementation will also be discussed.

Neonatal and pediatric transfusion practices and policies in India: A survey-based cross-sectional assessment of blood centers.

BACKGROUND: Blood centers play a critical role in supporting neonatal and pediatric transfusions. We aim to study the variation in pediatric/neonatal transfusion policies and practices for blood centers in India. STUDY DESIGN AND METHODS: This is a survey-based (45 question) cross-sectional assessment of blood centers in India supporting pediatric/neonatal transfusions. RESULTS: One hundred three centers responded to the survey (response rate 51.2%; 103/201). As a part of pretransfusion testing, use of "microtainers" was reported by 58.4% (59/101) centers and only 57.4% (58/101) centers provide antibody screening. In case of absence of maternal sample, type O negative blood is most commonly used (48.5%; 49/101), and in case of ABO incompatibility, 68.3% (69/101) use units compatible with both mother and newborn. Leukoreduced RBCs are provided by 89% (90/101) centers and irradiated products are provided by 48.5% (49/101). 82% (83/101) of centers reported not receiving requests for CMV negative units considering the high incidence of CMV-seropositivity in donors. Fresh units are defined as <7 days old by 44.5% (45/101) and <5 days old by 31.6% (32/101) centers. 97% centers reported SAGM suspended RBCs in inventory but only 67.3% (68/101) use them for top-up transfusions to neonates. Overall >80% centers use the buffy-coat method for platelet concentrates preparation. Volume-based (ml/kg) aliquots preparation is done by 88% (89/101), mainly using the sterile connecting device (84.6%; 83/98). CONCLUSION: This survey shows heterogeneity and lack of standardization in practices across blood centers in India and highlights the need for more studies to establish best practices for this vulnerable age group.

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.

Autoimmune hemolytic anemia in children: Clinical presentation and treatment outcome.

BACKGROUND: Autoimmune hemolytic anemias (AIHA) are characterized by the destruction of red cells following the production of autoantibodies directed against them. Although AIHA in children is usually self-limiting, many still succumb to the illness due to delay in the diagnosis and treatment. AIHA in children may be secondary to autoimmune diseases, drugs, or immune deficiencies. Early diagnosis and appropriate immunohematological evaluation can aid in the diagnosis and treatment. OBJECTIVE: To analyze the evaluation, treatment, and outcome of AIHA in children. METHODS: Prospective data of patients aged 0-18 years diagnosed with AIHA between June 2017 and May 2019 were collected. INTERVENTION: Prednisolone was the first-line agent in all; second-line agents included cyclosporine and rituximab. Red cell transfusion was given in those with severe anemia with cardiac decompensation. RESULTS: Eleven patients were diagnosed during the study period. Hemoglobin ranged from 1.2 to 9 g/dl. The initial presentation was severe anemia in 8 children and moderate anemia with thrombocytopenia in 3. The trigger was infection in 5. Polyspecific direct coomb's test (DCT) was positive in 10 patients. 2/10 polyspecific DCT-positive cases on further evaluation had immunoglobulin G (IgG) and C3d positivity, whereas rest 8 had only IgG. One infant was diagnosed with DCT-negative immunoglobulin A-mediated AIHA. 4/11 attained remission following the short course of prednisolone. Cyclosporine was used as the second-line agent in 2 and rituximab was used in 3. Seven children are in sustained remission and off medication. One died within 12 h of diagnosis. CONCLUSION: AIHA is not an uncommon problem in children and can vary in its clinical severity. Early and correct diagnosis helps in deciding appropriate treatment.

National blood donor vigilance programme of India: Analysis of donor adverse reactions reported during initial 2 years of implementation (2016 and 2017).

INTRODUCTION: The donor vigilance program is intended to collect and assess information on unexpected or undesirable effects or reactions resulting from blood donation. In this report, we discuss the analysis of the blood donor adverse reactions (DARs) reported in the National Blood Donor Vigilance Programme of India during the first 2 years of implementation. MATERIALS AND METHODS: DAR reporting form prepared and approved by the National Executive Committee of the Haemovigilance Programme of India was used to capture the data by the blood centers and submitted to Donor-Vigil software prepared and hosted by the official website of the National Institute of Biologicals. Data reported for the years 2016 and 2017 were reviewed, analyzed, and validated by independent transfusion medicine experts. RESULTS: During this period, a total of 19,98,101 donations denominator data were reported, in which 1,622,600 (80.9%) were valid. A total of 6091 DARs were reported, out of which 3980 (65.35%) were found valid. Only validated numerator and denominator data were included in the analysis. Generalized DARs were the most common type of DARs reported (83.7%), followed by "others" type (7.7%), localized (7.6%), allergic (0.4%), and complications related to apheresis (0.4%). The overall DAR rate was 2.45/1000 blood donations, which was higher in apheresis donations (3.07/1000) as compared to whole blood donations (2.39/1000). The DARs rates were higher in females (3.5/1000) compared to male donors (2.3/1000) and in the first time (2.5/1000) compared to repeat donors (2.15/1000). CONCLUSION: In this report, we concluded that younger age, first time, and female donors are more prone to DARs as compared to older age, repeat, and male donors. During the analysis of the data, we found some limitations, which can be improved by upgrading the reporting form and conducting regular continuing medical education (CMEs) of participant blood centers.

Survey based cross-sectional study to analyse the variation of practices at blood centres during COVID-19 pandemic in India.

India has almost 3,000 blood centres collecting more than 11 million units annually. Maintaining blood supply during the COVID-19 pandemic is a huge challenge. We conducted a cross-sectional study by an online survey to analyse the variation of practices across blood centers of India during this pandemic. A total of 196 blood centers completely responded to the online survey. Most of the blood centres who responded were part of Government hospitals (60 %), part of an academic institutes (55.6 %) and were directly supporting a COVID hospital (67.5 %). Almost 95.4 % blood centers reported reduction of blood donation mainly due to lockdown (50 %) and inability to conduct camps (17.3 %). Scheduling blood donations was one of the most difficult to implement strategy for maintaining adequate blood donation (40.2 %). Blood center manpower management was also a challenge and upto 48 % blood centers operated in two batches to ensure social distancing in blood banks and reduce the risk of exposure. Hemato-oncology (36.8 %) and obstetrics (33.7 %) were major utilizer of blood during the pandemic. There were marked variations in use of PPE by blood banks staff as well as strategies adopted while conducting immunohematology tests on COVID-19 positive patients samples. This pandemic has highlighted some of the major limitations of the health services but blood services have risen to the challenge and strived to maintain the blood supply chain while ensuring blood donor and staff safety. The wide variations in the practices adopted highlights the need for uniform guidelines for blood services in future pandemics.

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.

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India.

India is one of the most affected countries by COVID-19 pandemic; but little is understood regarding immune responses to SARS-CoV-2 in this region. Herein we examined SARS-CoV-2 neutralizing antibodies, IgG, IgM, IgA and memory B cells in COVID-19 recovered individual from India. While a vast majority of COVID-19 recovered individuals showed SARS-CoV-2 RBD-specific IgG, IgA and IgM antibodies (38/42, 90.47%; 21/42, 50%; 33/42, 78.57% respectively), only half of them had appreciable neutralizing antibody titers. RBD-specific IgG, but not IgA or IgM titers, correlated with neutralizing antibody titers and RBD-specific memory B cell frequencies. These findings have timely significance for identifying potential donors for plasma therapy using RBD-specific IgG assays as surrogate measurement for neutralizing antibodies in India. Further, this study provides useful information needed for designing large-scale studies towards understanding of inter-individual variation in immune memory to SARS CoV-2 natural infection for future vaccine evaluation and implementation efforts.

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.

Convalescent plasma to aid in recovery of COVID-19 pneumonia in a child with acute lymphoblastic leukemia.

The natural history of COVID-19 infection in children is still evolving as the pandemic unfolds. Few cases of severe and often fatal COVID-19 have been reported although the infection is mild in the large majority. Children with cancers are recognised as a high risk group for all infections. Since there aren't any definite treatment guidelines established in children with severe COVID, treatment is guided by adult recommendations which too are often not evidence based. We report the case of a 4-year-old girl with severe COVID-19 associated pneumonia who presented to us as febrile neutropenia. The use of convalescent plasma along with steroids and IVIG showed dramatic results in this child and she recovered without the need for any specific treatment. This is highlighted as one of the earliest cases that is reporting the use of convalescent plasma in a child; the first ever in a child with underlying malignancy.

IgA-mediated autoimmune hemolytic anemia in an infant.

Autoimmune Hemolytic anemia (AIHA) a relatively uncommon form of hemolytic anemia in children, occurs due to the premature destruction of red blood cells caused by presence of autoantibodies directed against antigens on RBCs. Warm reactive AIHA is the most common form due to IgG isotype of immunoglobulin class binding to autologous RBCs at 370C and confirmed with a positive DAT screening. We present a case of DAT-negative primary warm AIHA in an infant due to IgA antibody. A 10 month old male infant presented with dark colored urine and irritability for past two months, with associated history of fever, diarrhea and vomiting. He had received one red cell transfusion 10 days prior. On physical examination he had pallor with tachycardia without splenomegaly. On investigation his hemoglobin was 5.8 g/dl, WBC 25.9 × 103/mm3 and normal platelets counts. Peripheral blood smear had spherocytes and biochemical values showed high bilirubin and LDH. Immunohematological work up revelaed polyspecific DAT was negative but monospecific DAT screening showed strong (4+) positivity for IgA and a weak IgG positivity. The patient was diagnosed as IgA-mediated Warm AIHA and was started on prednisolone at 2 mg/kg/day following which hemoglobin improved over the next 2 months. After 2 weeks, prednisolone was tapered and stopped by the end of 3 months. Patients with clinical and laboratory evidence of acute hemolysis, an additional screening for IgA antibody may be done even in cases where poly-specific DAT is negative. Early detection helps in avoiding further investigations and provide efficient management.