BACKGROUND:Human Cellular Therapy Laboratories (HCTL) use liquid nitrogen (LN2) tanks to preserve human cells, tissues, and cellular and tissue-based products (HCT/Ps). Continuous monitoring and proactive maintenance of LN2 tanks are critical to ensuring product potency and safety. Contingency planning is necessary to protect irreplaceable HCT/Ps should LN2 storage failure occur. Here we describe the management of 779 hematopoietic progenitor cell products (HPCs) and 7680 ampules from a failing tank in our HCTL. METHODS:A multidisciplinary working group, including HCTL technical staff, management, facilities, healthcare technology management (HTM), and leadership, was established to manage the at-risk HPCs. The group evaluated local resources and engaged geographic partners to support emergency storage relocation. The goal was to maintain temperature integrity, ensure safe transfer, and sustain uninterrupted operations. RESULTS:Over a 72-h period, 779 HPCs and 7680 ampules were relocated to on-site and off-site storage. Collaboration with a local partner provided LN2 dry shippers (DS), allowing transport of approximately 40 HPCs per trip to off-site storage. The operation was completed without loss of product integrity, and clinical operations proceeded uninterrupted. DISCUSSION:Frequent inspection and continuous monitoring of tanks are crucial for early detection of potential failures. Rescuing HPCs from a failing tank is challenging and carries risks to product integrity and staff safety. Careful contingency planning, including access to backup storage, LN2 DSs, and trained personnel, is essential for mitigating catastrophic tank failure.
BACKGROUND:The increasing diversity of blood donor populations has created new challenges for transfusion services worldwide. The identification of donors lacking relevant high-prevalence antigens is becoming increasingly important to ensure compatible blood products for alloimmunized patients and to support the development of rare donor registries. CD36 (ISBT 045) is a glycoprotein expressed on platelets, monocytes, and erythroid precursor cells. CD36 deficiency has been reported across multiple populations and is of relevance due to its association with anti-CD36 isoantibodies, which may cause platelet transfusion refractoriness and fetal/neonatal alloimmune thrombocytopenia. STUDY DESIGN AND METHODS:We analyzed CD36 expression in 1250 blood donors of diverse ancestry using flow cytometry. CD36-negative samples underwent molecular characterization using Sanger sequencing and next-generation sequencing of genomic DNA, complemented by cDNA analysis and cloning to investigate transcript-level alterations. RESULTS:We identified CD36 deficiency in 27 donors (2.16%). Genomic sequencing revealed 18 distinct coding variants, including three novel variants, most in the heterozygous state. In one CD36-negative donor, cDNA analysis demonstrated a 52-bp deletion in exon four and complete skipping of exon 9, despite the absence of splice-site variants in genomic DNA. Cloning confirmed coexistence of aberrant and wild-type transcripts in this individual. CONCLUSION:Our findings demonstrate that CD36 deficiency can arise from transcript-level defects in the absence of detectable coding or splice-site variants. These results indicate that genomic sequencing alone may be insufficient to fully resolve CD36-negative phenotypes and highlight the importance of integrating transcriptomic approaches to improve molecular diagnostics and transfusion support in increasingly diverse donor populations.
BACKGROUND:Remediation of physician learners is not infrequently discussed in the graduate medical education (GME) literature. However, none of this literature is specific to blood banking/transfusion medicine (BB/TM) fellows and their typical 1-year fellowship program. Identifying a fellow's deficiencies and establishing an effective remediation program during a time-limited BB/TM fellowship is challenging. STUDY DESIGN AND METHODS:GME literature on remediation of physician learners was reviewed. A group of current and former BB/TM fellowship directors convened virtually to discuss if and how this literature could apply to BB/TM fellowships. Possible best practices in the remediation of BB/TM fellows were then recommended. RESULTS:Challenges in the remediation of BB/TM fellows were identified, including the limited duration of the fellowship, the often-small number of faculty available for remediation activities, and faculty unfamiliarity with remediation techniques. Beyond these challenges, many remediation best practices can be gleaned from the GME literature, including adequately documenting a fellow's deficiencies and any remediation programs implemented, as well as involving institutional GME leadership early in remediation efforts. DISCUSSION:Remediation of any physician learner can be difficult, but remediation of BB/TM fellows has unique challenges. Providing discipline-specific insights into remediation may make the remediation of BB/TM fellows more effective and improve the competency of future physicians in the field.
BACKGROUND:Plerixafor (P) is a rescue mobilization agent given to improve circulating CD34+ for peripheral blood stem cell (PBSC) collection in donors with inadequate response to granulocyte colony-stimulating factor (G-CSF, [G]). In this study, we evaluated the impact of immediate plerixafor administration without leukapheresis interruption for the same-day PBSC collection in G-mobilized allogeneic donors with pre-apheresis peripheral blood CD34+ count ≤30/μL. STUDY DESIGN:Retrospective analysis of two-center data from 10/2023 to 11/2025 was conducted. The study group (G + P) received G-CSF for 5 days and plerixafor without leukapheresis interruption (n = 12). The control group (G, n = 24) received 5-day G-CSF and had similar median apheresis procedure time as study group. Outcomes were evaluated at early procedure (EP) and late procedure (LP) periods, separated by the timing of the interim PBSC product characterization. RESULTS:G + P donors did not experience increased platelet loss or grade 2 or greater adverse reactions in gastrointestinal and immune systems or required day-2 collection. During the LP period, G + P group had approximately 5.5-fold increase in median CD34+ cells/L processed/h apheresis (p < .0001). During the LP period, while G + P group had significant gains in CD34+ yield, there was a significant loss in the control group (p < .0087). CD34+ collection efficiency was significantly higher in G + P (p < .0001). All PBSC products from G + P group contained ≥4.5 × 106 CD34+/kg recipient while only 63% of controls met this threshold (p = .016). CONCLUSIONS:Same-day rescue plerixafor without leukapheresis interruption in allogeneic donors suboptimally responding to G-CSF results in safe and efficient leukapheresis collection while preserving PBSC product quality.
BACKGROUND:The cluster of differentiation 44 glycoprotein carries the Indian blood group system, including the antithetical antigens Ina and Inb. The Inb antigen is highly prevalent, with more than 99.9% of Caucasians being Inb-positive, whereas Inb-negative individuals are found almost exclusively in South Asian populations (~0.02%). Anti-Inb can cause hemolytic transfusion reactions, but little data are available on hemolytic disease of the fetus and newborn (HDFN), suggesting minimal placental transfer, with only one reported case of a positive neonatal direct antiglobulin test (DAT). CASE REPORT:A woman of Indian origin developed an anti-Inb alloantibody with a titer of 64 during her first pregnancy. This was detected only at delivery, with no evidence of transplacental transfer of antibodies or HDFN. The anti-Inb titer increased after delivery, reaching a peak of 1024, and remained stable throughout the second pregnancy. At birth, the second neonate showed a strongly positive DAT, with anti-Inb detectable in both the plasma and eluate, confirming transplacental transfer and red blood cell binding. Testing of maternal plasma showed immunoglobulin G1 predominance over immunoglobulin G3 and moderate-to-high hemolytic potential in the monocyte monolayer assay and antibody-dependent cellular cytotoxicity (ADCC) test, with a monocyte index of 7.7-10% and ADCC of ~40%. Despite these findings, the neonate exhibited no signs of hemolysis. CONCLUSION:This case demonstrates that high-titer, functionally active maternal anti-Inb antibodies can coexist with neonatal anti-Inb reactivity without causing hemolysis. The marked discrepancy between serological, functional, and clinical findings underscores the limited predictive value of current assays in rare blood group incompatibilities.
BACKGROUND:CD47-targeted agents can interfere with pretransfusion testing due to CD47 expression on red blood cells (RBCs). IMC-002 is a novel anti-CD47 human IgG4 monoclonal antibody engineered to minimize RBC binding; however, its interference profile during pretransfusion testing remains poorly characterized. STUDY DESIGN AND METHODS:Whole blood samples were incubated with IMC-002 and tested by tube, gel card, and automated methods for ABO/RhD typing, direct antiglobulin test (DAT), and RBC phenotyping. Plasma spiked with IMC-002 underwent antibody screening by tube and gel methods, adsorption studies, and carryover assessment. Flow cytometry compared IMC-002 binding between RBCs and T cells. RESULTS:IMC-002 interfered with ABO/RhD typing, DAT, and antibody screening, but the extent varied by assay. Forward grouping interference was mitigated by saline washing. In contrast, reverse grouping interference was most prominent in gel cards but was resolved in tube testing via saline replacement. Antibody screening showed panreactive false-positive results, which were stronger in gel cards and with papain-treated RBCs. However, the magnitude of interference was lower than that reported for other CD47-targeted agents. Flow cytometry confirmed minimal IMC-002 binding to RBCs compared to dose-dependent binding to CD3+ T cells. CONCLUSIONS:IMC-002 exhibits a distinct pretransfusion interference profile compared with previously reported CD47-targeted agents. Its interference appears partly mitigable by routine laboratory measures and is consistent with its engineered low RBC affinity, underscoring the need for agent-specific evaluation of CD47-targeted therapeutics in transfusion practice.
BACKGROUND:Plasma has been used as an efficient resuscitation fluid to improve prehospital survival from hemorrhagic shock. The 25% albumin (25% ALB, w/v in aqueous diluent) is a hyperoncotic fluid, and we hypothesize that it can be used as a lower-volume alternative to plasma in hypovolemic shock. METHOD:Isoflurane-anesthetized Sprague-Dawley rats were subjected to a lethal decompensated hemorrhagic shock via removing 65% estimated blood volume (EBV, calculated by 6% body weight (gram) + 0.77 mL) of blood within 20 min. At 20 min post-hemorrhage, rats randomly received plasma (20% EBV), 25% ALB (4% EBV), or respective vehicles, followed by fresh whole blood (FWB, 20% EBV) at 1 h post-hemorrhage. The outcome was also compared between plasma and 25% ALB without FWB resuscitation in a separate experiment. RESULTS:20% EBV of plasma or 4% EBV of 25% ALB led to 100% survival at 60 min from the start of hemorrhage, compared to zero survival without treatment. Survival was maintained at least 4 h following limited resuscitation, with or without FWB at 1 h post-hemorrhage. The lack of fibrinogen in 25% ALB was notable and compromised the hemostatic outcome as compared to using plasma, which was partially restored by FWB resuscitation with the reduction in prothrombin time. CONCLUSION:The current study indicates that 25% ALB enhances survival and maintains hemodynamics at only one-fifth the volume of plasma. The results also suggest that 25% ALB requires hemostatic agents or subsequent blood products to counteract the hemostatic deficiency caused by hemodilution.
BACKGROUND:In China, current blood donation eligibility criteria classify men who have sex with men (MSM) as ineligible to donate blood. We aimed to examine perceptions, attitudes, and blood donation behaviors among MSM in China. METHODS:We conducted a nationwide multicenter cross-sectional survey followed by qualitative interviews from April to July 2024. Survey data included sociodemographic characteristics, sexual behaviors, and awareness, attitudes, and experiences related to blood donation eligibility criteria. Multivariable modified Poisson regression was used to identify the correlates of prior blood donation and attitudes toward the eligibility criteria. Interviews explored motivations for blood donation and perceptions of the eligibility criteria. RESULTS:A total of 2725 MSM participated in the survey. 1255 (46%) were unaware that MSM were prohibited from donating blood in China, and 887 (33%) reported having previously donated blood. After all participants were introduced to the current eligibility criteria, 442 (16%) supported the criteria, and 934 (34%) opposed them. Prior blood donation was associated with positive attitudes toward blood donation and perceptions of the eligibility criteria. Qualitative interviews (n = 16) indicated that motivations for blood donation included contributing to society and securing priority access to blood products, while reliance on self-reported sexual behaviors was perceived to limit effective implementation of the criteria. CONCLUSIONS:Blood donation was common among MSM in China despite limited awareness of current eligibility criteria. These findings highlight the need for further research on how existing eligibility criteria are communicated, understood, and implemented in practice while maintaining blood safety as a primary consideration.
BACKGROUND:The RH blood group system, particularly the RH1 (D) antigen, is highly immunogenic and clinically significant in transfusion medicine. Standard serological donor RH1 typing may fail to detect very weakly expressed RH1 variants, resulting in a risk of alloimmunization in recipients negative for the corresponding antigen. In 2012, routine molecular screening of RH1-negative first-time donors was implemented in Switzerland to improve transfusion safety. In this context, we present three novel RH1 variant alleles discovered through molecular analysis. METHODS:Serological RH phenotyping was performed using column agglutination, adsorption-elution testing, and monoclonal antibody panels. Genomic DNA and RNA were extracted and analyzed by SSP-PCR, RHD exon sequencing, and cDNA sequencing. RESULTS:Three previously undescribed RHD variant alleles were identified in four first-time donors. Two donors carried a nonsense mutation NM_016124.5:c.265C>T resulting in a premature stop codon (NP_057208.2:p.Gln89Ter), associated with an apparent RH1-negative phenotype but weakly positive adsorption-elution results. One donor carried a missense mutation NM_016124.5:c.863 T>A (NP_057208.2:p.Ile288Asn), associated with extremely weak RH1 expression. In one donor with a true RH1-negative phenotype, a frameshift mutation NM_016124.5:c.970del was identified, resulting in NP_057208.2:p.His324Thrfs*35 and predicted truncation of the RH1 protein. DISCUSSION:The findings demonstrate that routine molecular RHD screening of serologically RH1-negative first-time donors is essential for the detection of rare RHD variants that may escape serological testing. Molecular characterization of such alleles improves transfusion safety by preventing inadvertent transfusion of RH1-positive red blood cells to RH1-negative recipients and contributes to a more comprehensive understanding of RHD genetic diversity.
BACKGROUND/CASE STUDIES:Efficient blood and blood components supply is key to the stable operation of a health care system, especially to a civilian population and military under martial law. The blood system is an important component of a state's defense capability and national security. Since 2022, Ukraine has advanced experience in self-sufficiency with whole blood and blood components in the conditions of a land war, without importing blood components. STUDY DESIGN/METHODS:In October 2022, a Ukrainian transfusion medicine delegation-headed by Specialized State Institution «Ukrainian Transplant Coordination Center» (SSI «UTCC»), the national coordinator of Ukraine's blood system-visited several Midwestern US blood banks, including Northwestern Memorial Hospital, to exchange information on blood system organization, transfusion practice, and disaster preparedness. During a daylong seminar and follow-up communications, delegation members described the Ukrainian blood system, wartime challenges, and plans to meet European Union standards, while also learning about US laboratory standards, transfusion practices, and emerging blood components such as cold-stored platelets. The approaches presented during this exchange have since demonstrated sustained effectiveness and systemic resilience across subsequent years of full-scale conflict, through to the present day. RESULTS/FINDINGS:In 2021, Ukraine had 24 regional blood establishments and 385 hospital blood banks collecting whole blood and blood components. The donor rate was 7.5 per 1000 inhabitants, and 44% of donors were first-time donors. Most donors (95%) were voluntary donors aged 18-45 years. The national blood system served both civilian and military needs. Since the invasion, some blood establishments and hospital blood banks have been damaged, destroyed, or occupied. These disruptions created urgent challenges, including coordination of blood system activities to maintain a continuous blood supply for civilian and military healthcare systems, management of the donor pool, development and management of national whole blood and blood component inventories, implementation of new transfusion practices and basic transfusion training for the security and defense forces, and traceability and hemovigilance during the prehospital stage of medical evacuation. In response, the Ministry of Health of Ukraine established the Operational Headquarters to coordinate the blood system under martial law. Blood establishments now report blood stocks daily, and some operate on a 24-h cycle to increase collection volumes. New approaches to donor recruitment and blood collection were developed to improve donor safety, and organizational partnerships and national donor campaigns were launched, including "Your blood can fight. Become a donor." The production, supply, logistics, and redistribution of whole blood and blood components to areas of need were centralized and codified into law, resulting in a more efficient blood supply network. To meet emergency needs, group O Rh-negative whole blood was prioritized, followed by group-compatible red blood cells and lyophilized plasma. Despite severe wartime challenges, Ukraine's blood system has met the increased demand for transfusion support since the start of the invasion without relying on imported labile blood products. CONCLUSIONS:Military conflict, particularly land war, presents unique challenges to blood establishments and current transfusion practices that require urgent solutions. Exchange of experience on these issues strengthens the capacity of the blood system, defense capability and national security of states.
BACKGROUND:Frequent plasma donation is associated with reduced circulating IgG levels, prompting many jurisdictions to apply IgG-based deferral thresholds as a precautionary donor-safety measure. However, whether low IgG in healthy individuals reflects clinically meaningful immunosuppression remains unclear. This study evaluated IgG as a marker for donor health by integrating immunological, behavioral and self-reported outcomes, including vaccine responses, return to donation, and health problems. STUDY DESIGN AND METHODS:The kinetics of IgG decline associated with frequent plasma donation were analyzed over 18 months in 49 first-time and 50 repeat donors. Vaccine responses were evaluated in repeat donors with low or high IgG using ELISA to measure SARS-CoV-2 Spike receptor-binding domain antibodies and avidity after primary and booster COVID-19 vaccination. Return to plasma donation was examined in 3897 first-time plasma donors followed up to 22 months. Self-reported health problems were analyzed in 5347 plasma donors over 10 years. RESULTS:IgG levels declined during early donations in first-time donors but stabilized thereafter, suggesting a new homeostatic set point rather than progressive IgG depletion. All vaccinated donors seroconverted after primary vaccination regardless of IgG level. Although antibody levels were slightly lower in low-IgG donors, affinity maturation was comparable after boosting. IgG levels were not associated with return to donation or increased self-reported health problems. DISCUSSION:Low IgG levels in healthy plasma donors were not associated with impaired immunity, donor retention, or increased self-reported health problems. These findings support cautious interpretation of isolated IgG values in donor management and favor longitudinal monitoring over fixed thresholds.
BACKGROUND:Antibody identification testing is essential for preventing hemolytic transfusion reactions from unexpected red cell antibodies. Although automated interpretation is desirable to improve efficiency and consistency, conventional algorithmic approaches show limited accuracy, particularly in complex cases. Large language models (LLMs) offer a potential alternative; however, their performance is known to be sensitive to tabular data, which is a standard format for antigen profiles in antibody identification. STUDY DESIGN AND METHODS:We generated 100 simulated antibody identification cases comprising single alloantibodies, dual alloantibodies, autoantibodies, and unidentifiable patterns. Seven LLMs (GPT-4o, GPT-4.1, o3, GPT-5, Gemini 2.0 Flash, Gemini 2.5 Flash, and Gemini 2.5 Pro) were evaluated. Antigen profile tables were provided using five text-based formats (Markdown, CSV, JSON, list-based, and sentence-based serialization) and as uploaded spreadsheet files. Each model interpreted all cases 10 times per format, and accuracy was assessed overall and by antibody category. RESULTS:Reasoning-capable LLMs significantly outperformed non-reasoning models, achieving a median accuracy of 84.5%. Among text-based formats, sentence-based serialization yielded the highest accuracy, whereas CSV performed poorest. The maximum accuracy difference between table formats reached 40.5 percentage points. GPT-5 and o3 performed comparably when antigen profiles were supplied as uploaded spreadsheet files, achieving accuracy similar to that of the sentence-based format. CONCLUSIONS:Reasoning LLMs demonstrated measurable baseline capability for interpreting antibody identification results when accompanied by appropriately structured antigen profile inputs. However, performance varied markedly with data representation and case complexity, and the use of LLMs in transfusion practice should remain limited to an assistive role under specialist supervision.
BACKGROUND:To maximize the utilization of cold-stored platelets (CSPs) in preclinical research, the use of small-volume storage bags (mini-bags) or tubes would allow multiple treatment groups to be investigated from a single component. It is necessary to determine the effect of using downscaled storage formats on CSP quality and function. METHODS:Mini-bags were prepared by vacuum sealing platelet storage bags to ¼ the standard size. Apheresis platelets (n = 8) in 40% plasma/60% PAS-E (SSP+) were aseptically aliquoted into mini-bags (30 mL) or polypropylene tubes (15 mL; CSP-tubes), and the remaining volume (~190 mL) was retained in the original bag (control). Platelets were refrigerated (2-6°C), and in vitro quality parameters were assessed over 21 days. RESULTS:Metabolic capacity was altered for CSP-tubes, with a significant decline in pH, mitochondrial membrane depolarization, and rapid glycolysis. CSP-tubes had greater storage-related activation, as evidenced by a higher proportion of annexin-V-positive platelets and a greater number of CD61+/annexin-V+ extracellular vesicles (EVs). Similarly, platelet functional capacity in CSP-tubes was compromised, with reduced clot strength compared to controls. CSPs stored in mini-bags remained comparable to controls, with the exception of a greater proportion of annexin-V-positive platelets and EVs at day 21. Importantly, despite these changes, no functional deficits were observed in mini-bag components. CONCLUSIONS:Storage in tubes markedly impairs the metabolic, structural, and functional quality of CSPs, indicating that this approach is unsuitable. In comparison, mini-bag storage preserves key in vitro parameters, supporting a scalable strategy that maximizes the utilization of CSPs for preclinical evaluation.
