Prevention strategies for vasovagal reaction in whole blood donors: A quadri-armed randomised control trial.

INTRODUCTION: Vasovagal reaction (VVR) is a frequently encountered generalised donor adverse reaction, associated with donor deterrence towards future donation. Several mitigation strategies for prevention of VVR were tried but still not standardised. This quadri-armed randomised study evaluated the utility of water ingestion, applied muscle tension (AMT) and combination of both in preventing the VVR among blood donors. METHODS: A quadri-armed randomised controlled trial was performed on 4320 whole blood donors. Blood donors of 18-65 years of age were randomised into four groups based on the interventions performed i.e., control with no intervention (Group 1, n = 1081), water ingestion (Group 2, n = 1082), AMT (Group 3, n = 1070) and combined intervention (Group 4, n = 1087). VVR during and immediately after blood donation were observed along with assessment of risk factors in blood donors and the effectiveness of interventions were analysed. RESULTS: The incidence of VVR observed 1.6% in our study, with the highest occurrence in the control group (2.5%) and the lowest in the combined intervention group (0.9%). Multivariable logistic regression revealed that the control group donors faced a 1.38-fold greater risk of VVR compared to those receiving interventions (OR: 1.38, 95% CI: 1.10-1.75). Other risk factors included younger age (OR: 1.5, 95% CI: 1.05-2.17), first-time donation (OR: 5.7, 95% CI: 1.66-5.74), prior history of VVR (OR: 2.5, 95% CI: 10.4-101.52). DISCUSSION/CONCLUSION: The combined approach of water ingestion and AMT proved significantly more effective in VVR prevention compared to individual interventions.

Notification and follow-up of blood donors reactive for transfusion-transmitted infections: A narrative review of the literature from India.

BACKGROUND AND OBJECTIVES: Notifying blood donors of their reactive status for transfusion-transmitted infections (TTIs) plays a vital role in enabling early diagnosis and management while also preventing these donors from making future donation and transmission of the infectious agent. Given the limited data on donor notification processes in India, a narrative review was conducted to assess the existing notification process and identify areas requiring enhancement. MATERIALS AND METHODS: We conducted literature searches using PubMed, Google Scholar and Scopus, employing various keywords. The review included data on the year of the study, study design, donor numbers, TTI screening methods, sero-reactive donor confirmation, notification frequency and methods, donor responses, post-test counselling and risk factor assessment. RESULTS: Out of the 29 identified articles, 16 studies were included in the analysis. Repeat testing for initially reactive results was conducted in nine studies for 24.3% reactive donors. Phone calls were the primary notification method in most studies (8; 50%), with letters sent in cases of no response. Only 12 studies provided data on notified donors, revealing a notification rate of 71.2%. Of all initially reactive donors, 33.3% sought post-test counselling. Data from six studies indicated that 74.3% of responsive donors had identifiable TTI risk factors. CONCLUSION: Our review revealed significant variability in the notification processes across different studies. To enhance the management of TTI-reactive donor notifications and responses, we recommend the establishment of universal protocols encompassing pre-donation counselling, repeat/confirmatory testing, notification methods and comprehensive follow-up and treatment.

Efficacy and safety of plerixafor in pediatric cancer patients undergoing peripheral blood stem cell harvest for autologous hematopoietic stem cell transplant.

Plerixafor for peripheral blood hematopoietic stem cell (PB HSC) mobilization in children undergoing autologous hematopoietic stem cell transplantation is primarily used following failure of the initial mobilization attempt. Data on plerixafor use in pediatric patients are limited. This retrospective study conducted at a single tertiary care center in India, details the efficacy and safety of plerixafor for 10 children with relapsed/refractory solid tumors or lymphomas. High risk neuroblastomas (HR NB) underwent autologous HSCT as part of consolidation. Plerixafor was administered at a dose of 240 µg/kg body weight of the recipient, subcutaneously, approximately 11-12 h prior to harvest. Ten patients (eight males, two females), with a median age of 8 years (range 2-18 years), received plerixafor prior to PB HSC harvest. All patients were administered granulocyte colony stimulating factor (GCSF) before the administration of plerixafor. The median CD 34 count for all patients pre-plerixafor was 29/µL, nine patients exhibited higher CD 34 post plerixafor (median of 148/µL). In nine patients, the values of the CD 34 count and total leukocyte count (TLC) of the harvested product were available, and in all cases, we achieved a good yield. All patients in this study were heavily chemotherapy pre-treated, and the use of plerixafor resulted in a satisfactory yield of peripheral blood stem cells. No side effects were observed.

Circulating plasma miR-23b-3p as a biomarker target for idiopathic Parkinson's disease: comparison with small extracellular vesicle miRNA.

Background: Parkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques. Methods: A total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker. Results: In RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04, p < 0.05) and 16.54% downregulated (fold change -1.04 to -7.28, p < 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was "upregulated" (p = 0.002) in plasma, whereas "downregulated" (p = 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086, p = 0.0029) and plasma-derived sEVs (AUC = 0.7278, p = 0.0483) of PD and age-matched controls. Conclusion: We observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control.

A rare report of H-partially deficient, non-secretor phenotype from India. An Ah like the rèunion and unlike a Para Bombay-Clarifying misinterpretations.

BACKGROUND: H-deficient phenotypes are classified as H-deficient non- secretors (Bombay Oh), H-deficient secretors (Para Bombay), and H-partially deficient non-secretors (O h reunion, Ah and Bh, ABh). REPORT: We report the first case of H-partially deficient non-secretor- the Ah phenotype from India. What makes this report interesting is that they do not fit into the Bombay, or the Para Bombay series of H-deficient phenotypes and these partially deficient non-secretors were exclusively found on Réunion Island, off the East Coast of Africa in 1982. These reunion type phenotypes have not been reported since then and may lead to misinterpretations and confusions when encountered in the current existing laboratory settings especially in the low income (LIC's) and low middle income (LMIC's) countries like our own. Moreover, literature from LMIC and LIC incorrectly uses Ah/Bh for parabombay phenotypes. CONCLUSIONS: H-deficient phenotypes are rare, challenging to identify and assign correct notations. Hence, we have highlighted characteristic differences between H-deficient phenotypes and illustrated a diagnostic laboratory approach to correctly identify and assign notations to them especially in the resource constrained settings.

Establishment of normal reference range of serum hepcidin in Indian blood donors.

BACKGROUND: Hepcidin-25, a polypeptide hormone, plays a major role in iron metabolism and is found to be reduced during iron deficiency; therefore, testing for hepcidin can be utilized as an indicator of bioavailability of iron. Globally, reference range values for hepcidin have been established in different communities. The aim of the present study was to establish the normal reference range values of serum hepcidin in Indian blood donors to fathom the baseline and reference point of hepcidin. MATERIALS AND METHODS: A total of 90 donors fulfilling the eligibility criteria were recruited in the study consisting of 28 males and 62 females. Blood samples collected were used to execute hemoglobin (Hb), serum ferritin, and hepcidin assays. Serum hepcidin-25 isoform was detected by a commercial competitive enzyme-linked immunosorbent assay kit according to the manufacturer's instructions. Hb and ferritin were evaluated by the standard methods. RESULTS: The mean ± standard deviation (SD) of Hb level in males was 14.62 ± 1.34 g/dL and females was 13.33 ± 0.76 g/dL. The mean ± SD of ferritin level in males was 113 ± 56.12 ng/mL and females was 62.65 ± 40.8 ng/mL. Similarly, the mean ± SD of hepcidin level in male donors was 22.18 ± 12.17 ng/mL and female donors was 10.95 ± 6.06 ng/mL. The established reference range values of Hepcidin were 6.32-46.06 ng/mL for males and 3.44-24.78 for females. CONCLUSION: These findings suggest that further studies with larger groups of donors are mandatory to produce reference values of hepcidin that can be précised to the whole populace in India.

Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples.

Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC-MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value < 0.001), TNF-α (p-value = 0.025) and s-CTLA4 (p-value = 0.08) were higher in SCLC patients while IL-2 was lower (p-value = 0.003) as compared to healthy controls. IDO1 activity was significantly elevated in SCLC cohort (p-value = 0.007). We proffer that SCLC patients show immune suppressive milieu in their peripheral circulation. Analysis of CTLA4 immunohistochemical expression along with s-CTLA4 levels appears prospective as biomarkers for predicting responsiveness to ICPIs. Additionally, evaluation of IDO1 appears cogent both as prognostic marker and potential therapeutic target as well.

Critical appraisal of knowledge, attitude and practice studies for blood donation in India.

BACKGROUND AND OBJECTIVES: A critical appraisal of the literature helps to assess the strength and weakness of the research and suggests ways to improve future research. Our aim was to critically appraise the knowledge, attitude, and practice (KAP) studies conducted in India for blood donation. MATERIALS AND METHODS: Of 70 articles identified in our search on PubMed, Scopus and Google Scholar, 32 were assessed for quality using an appraisal tool for cross-sectional studies (AXIS) and questionnaire items. RESULTS: Quality assessment revealed that only 6 of 32 studies had acceptable reporting (≥80% score on the AXIS tool). The most frequently identified shortcomings were failure to address the non-responders, lack of justification for sample size, assessment of outcome variables and demographic results for the survey. Our evaluation of questionnaires revealed that knowledge for need for blood donation, its benefits and site/place for blood donation were assessed by very few studies. With this, issues such as parental/family consent, religious beliefs, and indifference to blood donation process were amongst the common reasons for non-donation. Many studies also failed to ask questions related to procedural information/instructions, which are necessary for promoting voluntary blood donations. CONCLUSION: Most published KAP studies for blood donation in India were not appropriately described, especially the methodology and result section. These deficiencies could have led to suboptimal interpretation of the prevalent issues. Use of an open-ended and validated KAP questionnaire with a problem-based approach and inclusion of participants from various socio-cultural backgrounds is required for good quality of evidence.

Assessment of Transfusion Practices Among Doctors During COVID-19 Pandemic Using Questionnaire-Based Survey.

During COVID-19 pandemic, many doctors were redirected from various disciplines for care of COVID-19 patients. A survey was conducted among doctors involved, to assess transfusion practices during the pandemic. To assess the knowledge, attitude, and practices of blood transfusion among doctors involved in care of COVID-19 patients. A cross-sectional survey using an online questionnaire (Google form) was used to assess knowledge and need of transfusion, attitude towards modifications in transfusion process, and practices during pandemic. Analysis was done among subgroups based on experience (designation), user type (speciality) and frequency of blood usage in parent department. Of 1900 invitations, 437 responses were received from resident doctors and faculty members across various disciplines. Of these, 354(81%) participants were included in analysis. Mean knowledge score was 6.2, majority 297(83.9%) had adequate knowledge scores (≥ 5 of total 12). Knowledge levels were higher among frequent blood users. Positive attitude towards changes in transfusion process was observed in 72.9% participants with similar scores in subgroups. Practice was assessed in 222(62.7%) participants. Mean practice score was 6.9, wherein 57.7% participants had optimal scores (≥ 7 of total 14). Positive correlation was observed between attitude and practice, unlike knowledge and practice. Although most participants had demonstrated adequate transfusion knowledge levels and positive attitude, transfusion practices during pandemic were affected mainly due to shortage of blood components and modifications in transfusion requisition process due to stringent COVID-19 containment measures. Thus, indicating need for improvement in the basic understanding of the transfusion process. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01613-2.

Epidemiology of severe acute respiratory syndrome-related coronavirus 2 antibodies in healthy blood donors and their follow-up.

BACKGROUND: Asymptomatic/presymptomatic COVID-19 affected individuals who may appear healthy during blood donor screening can donate blood despite being infective. Most blood donors in India are relatives/friends/acquaintances of patients, who under peer pressure overlook the donor selection process, which can significantly impact the transfusion safety. AIMS: The prevalence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) antibodies among blood donors was assessed, along with the possible transmissibility of SARS-CoV-2 virus in transfusion recipients of blood components prepared from sero-reactive blood donors. SETTINGS AND DESIGN: A prospective cross-sectional study was conducted among eligible blood donors from November-2020 to April 2021. METHODS: 1500 blood donors were tested for SARS-CoV-2 IgG antibodies. Sero-reactive donors were followed-up telephonically to inquire about risk factors prior to donation or appearance of COVID-19 related symptoms postdonation. Patients transfused with blood components from seroreactive donors were also followed up for posttransfusion symptoms suggestive for COVID-19. Descriptive analysis was done for the donor and patient follow-up data. RESULTS: A total of 452 (30.1%) donor were reactive, with median S/CO ratio of 2.8 (interquartile range 1.5-5.5). Risk factors such as travel, contact, or quarantine were significantly higher among reactive donors. History of diabetes and/or hypertension was associated with seroreactivity. Total 516 patients were transfused with blood components from these seroreactive donors. Three patients developed fever after transfusion, one of which was found to be PCR positive after 4 days of transfusion. CONCLUSION: Sero-reactivity rate among blood donors was lower than the general population. Optimum blood donor screening strategies can help decrease the possibility of blood collection from infected blood donors.

Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility.

Background: Alcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD. Methods: Patients with alcohol use disorder with ALD (n = 128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined. Results: The CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype [ORTT, 95% CI = 2.19, 1.16-4.13 for ALD vs. ALC and OR, 2.09, 1.18-3.72 for ALD vs. NALC]. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1ß, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression. Conclusion: Enhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.

Residual risk estimates of transfusion transmissible hepatitis B, hepatitis C and human immunodeficiency virus using nucleic acid testing yield/window period model in an Indian setting.

BACKGROUND: Estimation of residual risk (RR) is necessary to understand status of blood safety with current testing strategies and need to improve it further. These estimates from India are lacking till date. Present study was aimed to estimate RR and incident rate (IR) of transfusion transmitted infectious disease (TTIDs) in Indian setting. STUDY DESIGN AND METHODS: Blood donor demographic data, serological testing results and nucleic acid testing (NAT) screening results were collected retrospectively from January 2015 to June 2017. Mathematical modelling using NAT yield/window period model was done to estimate IR and RR of TTIDs. Data was compared between different groups based on age-group, gender, donation repeatability and type of donor. RESULTS: A total 106 119 blood donors donated 109 441 units with overall TTID reactivity of 2.22%. HBV was most prevalent TTID (1.26%) with RR of 16.1 per million followed by HCV and HIV with RR of 4.4 and 3.1 per million donations, respectively. NAT testing variably reduced RR ranging from 69.4% to 96.1% depending on TTID. Younger, repeat and voluntary donors had significantly lower prevalence of TTIDs compared to older, first time and replacement donors. DISCUSSION: Gaps in the blood safety could be bridged significantly by implementing NAT testing and using quality serological assays. Comparatively high RR despite using quality serological assays and ID-NAT testing highlights need to develop long term strategies to improve blood safety by focusing on improving donor pool by recruiting regular voluntary donors among youth and imparting knowledge of healthy practices.

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.

Comparative evaluation of ADVIA Centaur® XP chemiluminescence system for screening of HBV, HCV, HIV and syphilis in Indian blood donors.

BACKGROUND: The introduction of chemiluminescent immunoassay (CLIA) in blood donor screening has led to a gradual replacement of enzyme-linked-immunosorbent assay (ELISA) as the former offers automation, higher sensitivity and lower turn-around-time. However, only a few CLIA platforms are used for blood donor screening in India. The present study evaluated one such newer platform viz., Adiva Centaur XP CLIA for screening of HBV, HCV, HIV and syphilis. MATERIAL AND METHODS: Prospective comparative study wherein 4843 whole blood donors were screened for HBsAg, Anti-HCV, HIV Ag-Ab and Anti-treponemal antibodies in both Advia Centaur XP and Architect i2000SR platforms. Additional tests were performed in samples which were reactive in only one of the platforms. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false positive rate and false negative rate of both the platforms were compared. Kappa coefficient was calculated to determine the agreement between the testing platforms. RESULTS: The sensitivity of Advia Centaur platform for HBV, HCV, HIV and syphilis detection were 94.9 %, 100 %, 100 % and 100 % respectively as compared to 96.6 %, 100 %, 100 % and 100 % in Architect i2000SR platform. The specificity of both the platforms were 99.8-99.9 % for all the four tests. The agreement between the two platforms was almost perfect for HBV, HCV and syphilis testing; and fair for HIV testing. CONCLUSION: The Advia Centaur CLIA platform was found to be comparable with the Architect CLIA platform for blood donor screening. Unexpected finding was the occurrence of HBV false negatives in both the platforms, possibly due to HBsAg mutations.