Expired blood transfusion and mortality outcomes in combat trauma patients.

BACKGROUND: Expired blood can be transfused if clinically indicated but outcome data do not exist. We hypothesized that modestly outdated blood can effectively support a hemorrhaging patient until surgical control is achieved. This study assessed whether expired blood was associated with mortality in combat trauma patients. STUDY DESIGN AND METHODS: A retrospective analysis of Armed Services Blood Program and Department of Defense Trauma Registry databases evaluated combat casualty records (2001-2023). The intervention of interest was transfusion of at least one unit of whole blood (WB), red blood cells (RBC), or platelets within one week past expiration. The outcome of interest was mortality at discharge. A control cohort that only received in-date blood was matched to the treatment cohort for logistic regression analysis. RESULTS: One hundred patients received expired RBCs (86), WB (11), and platelets (3). Mortality at discharge was 11.6% for expired RBC recipients and 13.4% for the control cohort (p = .97). After adjustment for injury severity, expired RBCs were not associated with mortality (OR = 0.40 [95% CI, 0.14-1.16]; p = .09). Of 10 patients who received the most expired RBCs by volume or storage duration, two were deceased at discharge. All 14 expired WB and platelet recipients were alive at discharge, but sample sizes were underpowered for regression analysis. DISCUSSION: Transfusion of modestly outdated RBCs was not associated with mortality in combat trauma patients. Expired WB and platelet recipients did well, but sample sizes were too small to draw significant conclusions. Expired blood should be further investigated for possible use in extenuating circumstances.

Massive transfusion protocol reactivation as a novel marker of physician team under-triage after injury.

BACKGROUND: Large trauma centers have protocols for the assessment of injury and triaging of care with attempts to over-triage to ensure adequate care for all patients. We noted that a significant number of patients undergo a second massive transfusion protocol (MTP) activation in the first 24 h of care and conducted a retrospective cohort study of patients involved over a 3-year period. METHODS: Transfusion service records of MTP activations 2019-2021 were linked to Trauma Registry records and divided into cohorts receiving a single versus a reactivation of the MTP. Time of activation and amounts of blood products issued were linked to demographic, injury severity, and outcome data. Categorical and continuous data were compared between cohorts with chi-squared, Fisher's, and Wilcoxan tests as appropriate, and multivariable regression models were used to seek interactions (p < .05). RESULTS: MTP activation was recorded for 1884 acute trauma patients over our 3-year study period, 142 of whom (7.5%) had reactivation. Factors associated with reactivation included older age (46 vs. 40 years), higher injury severity score (ISS, 27 vs. 22), leg injuries, and presentation during morning shift change (5-7 a.m., 3.3% vs. 7.7%). Patients undergoing MTP reactivation used more RBCs (5 U vs. 2 U) and had more ICU days (3 vs. 2). CONCLUSIONS: Older patients and those presenting during shift change are at risk for failure to recognize their complex injury patterns and under-triage for trauma care. The fidelity and granularity of transfusion service records can provide unique opportunities for quality assessment and improvement in trauma care.

The safety of ABO minor incompatible platelets transfusions using a rapid infuser.

BACKGROUND: Administering platelets through a rapid infuser is proven to be safe. However, the clinical significance of infusing ABO-incompatible platelets with red blood cells (RBCs) in a rapid infuser remains unclear. There is a theoretical risk that isoagglutinin in the plasma of a platelet unit can interact with RBCs and induce hemolysis. MATERIALS AND METHODS: Seven in vitro studies were performed including five cases (type A RBCs and type O platelets) and two controls (type A RBCs and platelets). Anti-A titers were measured in platelet units. An RBC unit and a platelet unit were mixed in the rapid infuser reservoir and incubated for 30 min. The primary outcome was the presence of hemolysis based on the following parameters: free hemoglobin concentration, hemolysis check, direct antiglobulin test (DAT), and direct agglutination. RESULTS: The post-mix DAT was positive for IgG in all test samples (5/5), and weakly positive for complement in 3/5. The changes in free Hb in test cases between measured and calculated post-mix spanned -2.2 to +3.4 mg/dL. Post-mix hemolysis check was negative in 3/5 and slightly positive in 2/5 cases, with no significant differences compared to the control case. Anti-A titers ranged from 16 to 512 and were not associated with hemolysis. All samples were negative for direct agglutination. CONCLUSION: Our study suggested that mixing ABO-incompatible platelets with RBCs in a rapid infuser does not induce in vitro hemolysis. These findings support the use of rapid infusers regardless of platelet compatibility in support of hemostatic resuscitation.

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.

Novel method for determining when a field-collected donor unit is sufficiently full.

BACKGROUND: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete. METHODS: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed. RESULTS: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g). CONCLUSION: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full.

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.

Variations in emergency hemorrhage panel turnaround times in 2 major medical centers using the same laboratory methods.

OBJECTIVES: Demand for rapid coagulation testing for massive transfusion events led to development of an emergency hemorrhage panel (EHP; hemoglobin, platelet count, prothrombin time/international normalized ratio, and fibrinogen), with laboratory turnaround time (TAT) of less than 20 minutes. Ten years on, we asked if current laboratory practices were meeting that TAT goal and differences were evident in TAT between the 2 major institutions in our system. METHODS: We identified EHPs ordered at our 2 largest hospitals, February 2, 2021, to July 17, 2022, comparing order to specimen draw time, specimen draw to specimen received time, laboratory analytic time, and total TAT results from emergency department and operating room. Site 1 houses a level I trauma center; site 2 includes tertiary care, transplant, and obstetrics services. RESULTS: In total, 1137 EHPs were recorded in our study period. Laboratory TAT was significantly faster at site 1 (~14 vs ~27 minutes, P < .01). Average laboratory TAT was under 20 minutes at site 1 but only for 50% of specimens at site 2. Outlier specimens were collection delays at site 1 and specimen processing delays at site 2. CONCLUSIONS: The EHP can be performed as rapidly as described. However, compromises in laboratory location, available personnel, and processing differences can degrade performance.

Cumulative Donor-Specific Antibody Threshold Predicts Platelet Transfusion Response in HLA-Alloimmunized Patients.

Up to a third of multiply transfused patients with hemato-oncologic conditions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence post-transfusion platelet corrected count increments (CCI) in patients with human leukocyte antigen (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 2,012 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 post-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 ≥ 10,000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively impacted 2-hour but not 24-hour post-transfusion 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. Further, 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. Where 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.