Racial-ethnicity group distributions of blood product use in acute trauma care transfusion.

BACKGROUND: Recent studies suggest Black patients are transfused less often and at lower hemoglobin levels than White patients. In elective surgery, Black and Non-White patients have greater estimated blood loss and transfusion frequency. We asked whether similar transfusion disparities are observable in acute trauma resuscitation. METHODS: In a single-center retrospective analysis of trauma registry/blood-bank-linked data from a large US trauma center, we identified all acute trauma patients 2011-2022. Our data sources permitted distinction of Race and Ethnicity and therefor binning as Non-White-race/not Hispanic plus any-race/Hispanic or White/not Hispanic. We tallied Injury Severity Scores mild through profound (ISS 1-9, 9-15, 16-25, >25), type (blunt vs. penetrating) and mechanism (firearms, etc.), and associated blood use overall and in the first, first four, and first 24 h, comparing results with chi square, p < .01. RESULTS: Overall, 50,394 (68.41%) acute trauma patients were classified as White and 23,251 (31.7%) as Other than White. White patients were more likely to receive any blood products (17.8% vs. 11.9%), but, for all measures of urgency/quantity, Non-White patients were transfused more often (respectively, first 4 h, 51.9% vs. 42.1%; ≥3u/first hour, 18.5% vs. 11.0%; ≥10u/24 h, 8.1% vs. 3.8%) (all p < .001). White patients were far more likely to have blunt injury than Non-White patients, (77.2% vs. 42.6%), less likely to have penetrating injury (10.1% vs. 14%) and far less likely to be injured by firearms (30.6% vs. 56.9%) (all p < .001). CONCLUSIONS: At our center, blood use in acute trauma resuscitation was associated with injury severity and mechanism, not race/ethnicity.

Cumulative donor-specific antibody threshold predicts platelet transfusion response in HLA-alloimmunized patients.

ABSTRACT: Up to a third of patients with hemato-oncologic conditions who have received multiply transfusions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence posttransfusion platelet corrected count increments (CCI) in patients with HLA-alloimmune platelet transfusion refractoriness remain less well elucidated. Recent advances in HLA antibody characterization using fluorescent bead-based platforms enable the study of donor-specific antibody (DSA) avidity (as measured by mean fluorescence intensity [MFI]) and its impact on HLA-alloimmune platelet transfusion refractoriness. In this large retrospective study of 2012 platelet transfusions among 73 HLA-alloimmunized patients, we evaluated the impact of cumulative HLA DSA-MFI alongside other donor, platelet component, and patient characteristics on CCI at 2 and 24 hours after transfusion. As part of a quality improvement initiative, we also developed and tested a computerized algorithm to optimize donor-recipient histocompatibility based on cumulative DSA-MFI and sought other actionable predictors of CCI. In multivariate analyses, cumulative HLA DSA-MFI of ≥10 000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively affected 2-hour but not 24-hour posttransfusion CCI. The DSA-MFI threshold of 10 000 was corroborated by greater antibody-mediated complement activation and significantly more CCI failures above this threshold, suggesting the usefulness of this value to inform "permissive platelet mismatching" and to optimize CCI. Furthermore, DSA-MFI decreases were deemed feasible by the computer-based algorithm for HLA-platelet selection in a pilot cohort of 8 patients (122 transfusions) evaluated before and after algorithm implementation. When HLA-selected platelets are unavailable, ABO-identical/minor-mismatched platelet concentrates may enhance 2-hour CCI in heavily HLA-alloimmunized patients with platelet transfusion refractoriness.

A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

BACKGROUND: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes. STUDY DESIGN AND METHODS: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581). RESULTS: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty-seven outcomes were reported with a mean of 11 (min-max. 4-32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage. CONCLUSION: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion.

Hypocalcaemia upon arrival (HUA) in trauma patients who did and did not receive prehospital blood products: a systematic review and meta-analysis.

PURPOSE: Hypocalcaemia upon arrival (HUA) to hospital is associated with morbidity and mortality in the trauma patient. It has been hypothesised that there is an increased incidence of HUA in patients receiving prehospital transfusion as a result of citrated blood products. This research aimed to determine if there was a difference in arrival ionised calcium (iCa) levels in trauma patients who did and did not receive prehospital transfusion. METHODS: We conducted a systematic review and meta-analysis of patients with an Injury Severity Score (ISS) > / = 15 and an iCa measured on hospital arrival. We then derived mean iCa levels and attempted to compare between-group variables across multiple study cohorts. RESULTS: Nine studies reported iCa on arrival to ED, with a mean of 1.08 mmol/L (95% CI 1.02-1.13; I2 = 99%; 2087 patients). Subgroup analysis of patients who did not receive prehospital transfusion had a mean iCa of 1.07 mmol/L (95% CI 1.01-1.14; I2 = 99%, 1661 patients). Transfused patients in the 3 comparative studies had a slightly lower iCa on arrival compared to those who did not receive transfusion (mean difference - 0.03 mmol/L, 95% CI - 0.04 to - 0.03, I2 = 0%, p = 0.001, 561 patients). CONCLUSION: HUA is common amongst trauma patients irrespective of transfusion. Transfused patients had a slightly lower initial iCa than those without transfusion, though the clinical impact of this remains to be clarified. These findings question the paradigm of citrate-induced hypocalcaemia alone in trauma. There is a need for consensus for the definition of hypocalcaemia to provide a basis for future research into the role of calcium supplementation in trauma.

Effects of pre-freeze pathogen reduction with riboflavin and UV light on red cells stored post-thaw in AS-3 additive solution.

BACKGROUND: Pathogen reduction technology (PRT) may improve the safety of RBCs for transfusion. As the Czech Republic considers PRT, we asked what effects riboflavin and UV light PRT pre-freezing has on the post-thaw recovery and properties of cryopreserved RBCs (CRBCs) after deglycerolization and liquid storage. STUDY DESIGN AND METHODS: 24 Group O whole blood (WB) units were leukoreduced and then treated with riboflavin and UV light PRT (Mirasol, Terumo BCT, USA) before cryopreservation (T-CRBC); 20 similarly-collected units were untreated controls (C-CRBC). Units were processed to RBCs and then cryopreserved with 40% glycerol (wt/vol), frozen at -80°C, stored >118 days, reconstituted as deglycerolized RBC units in AS-3, and stored at 4 ± 2°C for 21 days. One treated unit sustained massive hemolysis during the post-thaw wash process and was removed from data analysis. The remaining units were assessed pre-PRT, post-PRT, and post-thaw-wash on days 0, 7, 14, and 21 for hematocrit, volume, hemoglobin per transfusion unit, pH, % hemolysis, hemoglobin in the supernatant, potassium, phosphorus, NH3 , osmolality, ATP, and 2,3-diphosphoglycerate. RESULTS: PRT with leukoreduction caused a 5% loss of RBC followed by a 24% freeze-thaw-wash related loss for a total 28% loss but treated units contained an average of 45 g of hemoglobin, meeting European Union guidelines for CRBC. T-CRBCs displayed higher post-wash hemolysis, potassium, and ammonia concentrations, and lower ATP at the end of storage. CONCLUSIONS: Cryopreserved RBCs from Riboflavin and UV light-treated WB meet the criteria for clinical use for 7 days after thawing and provide additional protection against infectious threats.

Epidemiological survey and screening strategy for dengue virus in blood donors from Yunnan Province.

BACKGROUND: Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies. METHODS: Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed. RESULTS: Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P < 0.001), and ethnicity (P = 0.026). CONCLUSION: The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials.

OBJECTIVE: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. BACKGROUND: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. METHODS: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. CONCLUSIONS: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

Quality management of a massive transfusion protocol.

BACKGROUND: Massive transfusion is a response to massive uncontrolled hemorrhage. To be effective, it must be timely and address the patient's needs for blood volume, oxygen transport, and hemostasis. STUDY DESIGN AND METHODS: A review was performed on all activations of the massive transfusion protocol (MTP) in a hospital with large emergency medicine, trauma, and vascular surgery programs. Indications, transfused amounts, and outcomes were determined for each MTP event to determine appropriateness of MTP use. Results are presented as descriptive statistics, categorical associations, and simple linear trend relationships. RESULTS: The MTP was activated 309 times in 2016. Of these episodes, 237 were for trauma, 29 for gastrointestinal bleeding, 16 for ruptured abdominal aortic aneurisms, and 25 for a variety of other causes. Trauma-related MTP activations had a mean injury severity score of 32. Blood use averaged 6.6 units of red blood cells (RBCs), 6.5 units of plasma, and 1.2 units of apheresis platelets. Fourteen activations ended without the administration of any blood products, and 45 (14%) did not meet the critical administration threshold of three components. Only 60 (19%) activations met the historic definition of massive with at least 10 units of RBCs administered. Mortality was 15% for the trauma-related activations. CONCLUSIONS: Massive transfusion protocol activations were frequent and conducted with high fidelity to the 1:1:1 unit ratio standard. Making blood components available quickly was associated with low rates of total component usage and low mortality for trauma patients and was not associated with overuse.

Massive Transfusion in Cardiac Surgery: The Impact of Blood Component Ratios on Clinical Outcomes and Survival.

BACKGROUND: Cardiac surgery is the most common setting for massive transfusion in medically advanced countries. Studies of massive transfusion after injury suggest that the ratios of administered plasma and platelets (PLT) to red blood cells (RBCs) affect mortality. Data from the Red Cell Storage Duration Study (RECESS), a large randomized trial of the effect of RBC storage duration in patients undergoing complex cardiac surgery, were analyzed retrospectively to investigate the association between blood component ratios used in massively transfused patients and subsequent clinical outcomes. METHODS: Massive transfusion was defined as those who had ≥6 RBC units or ≥8 total blood components. For plasma, high ratio was defined as ≥1 plasma unit:1 RBC unit. For PLT transfusion, high ratio was defined as ≥0.2 PLT doses:1 RBC unit; PLT dose was defined as 1 apheresis PLT or 5 whole blood PLT equivalents. The clinical outcomes analyzed were mortality and the change in the Multiple Organ Dysfunction Score (ΔMODS) comparing the preoperative score with the highest composite score through the earliest of death, discharge, or day 7. Outcomes were compared between patients transfused with high and low ratios. Linear and Cox regression were used to explore relationships between predictors and continuous outcomes and time to event outcomes. RESULTS: A total of 324 subjects met the definition of massive transfusion. In those receiving high plasma:RBC ratio, the mean (SE) 7- and 28-day ΔMODS was 1.24 (0.45) and 1.26 (0.56) points lower, (P = .007 and P = .024), respectively, than in patients receiving lower ratios. In patients receiving high PLT:RBC ratio, the mean (SE) 7- and 28-day ΔMODS were 1.55 (0.53) and 1.49 (0.65) points lower (P = .004 and P = .022), respectively. Subjects who received low-ratio plasma:RBC transfusion had excess 7-day mortality compared with those who received high ratio (7.2% vs 1.7%, respectively, P = .0318), which remained significant at 28 days (P = .035). The ratio of PLT:RBCs was not associated with differences in mortality. CONCLUSIONS: This analysis found that in complex cardiac surgery patients who received massive transfusion, there was an association between the composition of blood products used and clinical outcomes. Specifically, there was less organ dysfunction in those who received high-ratio transfusions (plasma:RBCs and PLT:RBCs), and lower mortality in those who received high-ratio plasma:RBC transfusions.

Restrictive versus liberal red blood cell transfusion strategy after hip surgery: a decision model analysis of healthcare costs.

BACKGROUND: Red blood cell transfusion related to select surgical procedures accounts for approximately 2.8 million transfusions in the United States yearly and occurs commonly after hip fracture surgeries. Randomized controlled trials have demonstrated lack of clinical benefit with higher versus lower transfusion thresholds in postoperative hip fracture repair patients with cardiac disease or risk factors for cardiac disease. The economic implications of a higher versus lower hemoglobin (Hb) threshold have not yet been investigated. STUDY DESIGN AND METHODS: A decision tree analysis was constructed to estimate differences in healthcare costs and charges between a Hb transfusion threshold strategy of 8 g/dL versus 10 g/dL from the perspective of both Centers for Medicare and Medicaid Services (CMS) as well as hospitals. Secondary outcome measures included differences in transfusion-related adverse events. RESULTS: Among the 133,697 Medicare beneficiaries undergoing hip fracture repair in 2012, we estimated that 45,457 patients would be anemic and at risk for transfusion. CMS would save an estimated $11.3 million to $24.3 million in payments, while hospitals would reduce charges by an estimated $52.7 million to $93.6 million if the restrictive transfusion strategy were to be implemented nationally. Additionally, rates of transfusion-associated circulatory overload, transfusion-related acute lung injury, acute transfusion reactions, length of stay, and mortality would be reduced. CONCLUSIONS: This model suggests that the uniform adoption of a restrictive transfusion strategy among patients with cardiac disease and risk factors for cardiac disease undergoing hip fracture repair would result in significant reductions in clinically important outcomes with significant cost savings.

The heritability of hemolysis in stored human red blood cells.

BACKGROUND: The transfusion of red blood cells (RBCs) with maximum therapeutic efficacy is a major goal in transfusion medicine. One of the criteria used in determining stored RBC quality is end-of-storage hemolysis. Between donors, a wide range of hemolysis is observed under identical storage conditions. Here, a potential mechanism for this wide range is investigated. We hypothesize that the magnitude of hemolysis is a heritable trait. Also, we investigated correlations between hemolysis and RBC metabolites; this will establish pathways influencing hemolysis as future targets for genetic analysis. STUDY DESIGN AND METHODS: Units of RBCs from identical and nonidentical twins were collected and stored under standard conditions for 56 days. Hemolysis, adenosine triphosphate (ATP), and total glutathione (tGSH) were measured throughout storage. Nontargeted metabolic analyses were performed on RBCs that had been stored for 28 days. Heritability was determined by comparing values between identical and nonidentical twins. RESULTS: Hemolysis was found to be heritable (mean > 45%) throughout the storage period. Potential correlations were observed between hemolysis and metabolites from the purine metabolism, lysolipid, and glycolysis pathways. These also exhibited heritability (>20%). No correlation was found with ATP or tGSH. CONCLUSION: The susceptibility of RBCs to lysis during storage is partly determined by inheritance. We have also uncovered several pathways that are candidate targets for future genomewide association studies. These findings will aid in the design of better storage solutions and the development of donor screening tools that minimize hemolysis during storage.

Overnight, room temperature hold of whole blood followed by 42-day storage of red blood cells in additive solution-7.

BACKGROUND: Overnight, room temperature hold (ONH) of whole blood before component processing offers several benefits. This study evaluated the storage and in vivo recovery characteristics of ONH red blood cells (RBCs) stored in additive solution-7 (AS-7). STUDY DESIGN AND METHODS: We conducted a three-center, three-arm evaluation of a new blood collection system with AS-7 compared to leukoreduced RBCs processed within 8 hours and stored in AS-1 (control). Whole blood (500 ± 50 mL) from healthy research subjects (n = 240) was held at room temperature 0 to 2 hours, 6 to 8 hours, or ONH (18-24 hr) before component processing and storage at 1 to 6 °C. RBCs were evaluated on Days 42 and 56 with a panel of in vitro assays. Subsets of the AS-7-stored RBCs were evaluated for (51) Cr 24-hour in vivo recovery and long-term survival. RESULTS: Adenosine triphosphate (ATP) levels in ONH RBCs were not different than AS-7 RBCs prepared within 8 hours. ATP was higher in the ONH group on Day 42 than control, and ATP was maintained in all AS-7 groups through Day 56. ONH units had 0.36 ± 0.14% on Day 42 hemolysis (60/60 < 0.8%), and 0.54 ± 0.22% on Day 56 (10/60 > 0.8%, 2/60 > 1%). In vivo recoveries of stored RBCs were not different between the AS-7 arms at 42 days (p = 0.16; 27/27 ONH units > 75%), but the Day 56 ONH was significantly less than ONH on Day 42 (p = 0.008; 7/28 < 75%). CONCLUSIONS: Overnight hold of whole blood at room temperature before component processing meets current regulatory requirements when RBCs are stored up to 42 days in AS-7.

Heritability of glutathione and related metabolites in stored red blood cells.

Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the "RBC storage lesion." There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage time and varies markedly between individuals. Oxidative damage is considered a significant factor in the development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG,2H(+)/2GSH couple (Ehc), and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107 mM, respectively, over 42 days). Taking into account the decline in pH, Ehc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study population heritability estimates for GSH, GSSG, tGSH, and Ehc measured over 56 days of storage are 79, 60, 67, and, 75%, respectively. We conclude that susceptibility of stored RBCs to oxidative injury due to variations in the GSH redox buffer is highly variable among individual donors and strongly heritable. Identifying the genes that regulate the storage-related changes in this redox buffer could lead to the development of new methods to minimize the RBC storage lesion.