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 We hypothesized that modestly outdated blood can effectively support a hemorrhaging patient until surgical control is achieved.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 DISCUSSION: Transfusion of modestly outdated RBCs was not associated with mortality in combat trauma patients.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.

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.

How do we perform intrauterine transfusions?

BACKGROUND: Intrauterine transfusion (IUT) is an invasive but critical and potentially life-saving intervention for severe fetal anemia with demonstrated improvement in outcomes. The fetus is vulnerable to hemodynamic alterations and transfusion-related adverse events; therefore, special consideration must be given to blood component selection and modification. There is widespread IUT practice variability, and existing guidance primarily relies on expert opinion and single center experiences. STUDY DESIGN AND METHODS: Experts in Maternal Fetal Medicine, Pediatric Hematology, and Transfusion Medicine from centers across the United States, collectively performing about 120 IUT annually, offer a multidisciplinary perspective on the performance of IUT and preparation of blood components. This perspective includes strategies for identifying an at-risk fetus, communicating between disciplines, determining the necessary blood volume, selecting and processing blood components, documenting the procedure in medical record, and managing the neonate. RESULTS: Identifying an at-risk fetus relies on review of the clinical history, non-invasive monitoring, and laboratory evaluation. We recommend the use of relatively fresh, group O, cytomegalovirus-safe, freshly irradiated, red blood cells (RBC) that are Hemoglobin S negative and antigen-negative for any maternal antibody, if indicated. These RBC units should be concentrated to remove additives and increase the hematocrit thus minimizing fluctuations in fetal volume status. The units intended for IUT should be labeled clearly and the documentation of transfusion differentiated in the maternal medical record. DISCUSSION: An awareness of the technical, logistical, and regulatory considerations for IUT performance will facilitate improved communication and patient care, especially when rare units of RBC are required.

How we approach transfusions in a patient with high risk of alloimmunization from McLeod phenotype.

McLeod phenotype-caused by the missing Xk protein-is a very rare red cell phenotype, one characteristic of McLeod syndrome, and sometimes associated with X-linked chronic granulomatous disease (CGD). Diagnosis of McLeod phenotype is important for appropriate transfusion management, because red blood cells from all healthy donors will have the Xk protein with its Kx antigen and can lead to red cell antibody formation without the ability to find compatible McLeod phenotype blood for transfusion. We offer a review and approach to diagnosis of the McLeod phenotype and special transfusion considerations.

Monitoring Direct Thrombin Inhibitors With Calibrated Diluted Thrombin Time vs Activated Partial Thromboplastin Time in Pediatric Patients.

OBJECTIVES: Activated partial thromboplastin time (aPTT) is the primary test used to monitor intravenous (IV) direct thrombin inhibitors (DTIs) but has many limitations. The plasma diluted thrombin time (dTT) has shown better correlation with DTI levels than aPTT. This study compared dose-response curves for dTT and aPTT in pediatric patients receiving argatroban and bivalirudin. METHODS: A retrospective review of pediatric patients treated with argatroban (n = 45) or bivalirudin (n = 14) monitored with dTT and aPTT. RESULTS: The dTT assay was calibrated to report DTI concentrations in µg/mL for argatroban and bivalirudin with good analytic sensitivity and specificity. The dTT was fivefold more likely to show a stable dose-response slope than the aPTT (P < .0002; odds ratio, 4.9). For patients in whom both dTT and aPTT showed a significant correlation between dose and assay results, dTT had a higher average correlation factor compared with aPTT (P = .007). Argatroban dose-response slopes showed more inter- and intrapatient variation than bivalirudin (dose-response slope coefficient of variation, 132% vs 52%). CONCLUSIONS: The dTT assay was more likely to show a stable dose response and have a stronger correlation with DTI dose than aPTT. Argatroban shows more variation in dose response than bivalirudin.

Drivers of blood use in paediatric trauma: A retrospective cohort study.

OBJECTIVES: We asked whether age or injury severity drives blood use patterns in paediatric trauma. BACKGROUND: Transfusion for paediatric trauma care is complicated by known developmental differences in coagulation and injury patterns. METHODS/MATERIALS: We linked 10 years of Trauma Registry and blood bank data, 2011-2020, for all acute trauma patients aged <18 treated at a large US Level 1 adult and paediatric trauma centre. We assessed age, injury severity and mechanism for association with any blood use, use within the first 4 h of care, and resuscitation balance, using grouped-age Chi-square and multivariable regression models. RESULTS: Of 60 066 acute trauma arrivals at our centre in the study period, 7979 (13.3%) met inclusion criteria. Median age (IQR) was (7.6[2.4-14.5]); 6230(78.1%) were < 15 years old; 590(7.4%) received any blood products; and 128(1.6%) died. Among the 5842(73.2%) patients with impact-related injury, 2023(34.6%) met standards for severe injury (New Injury Severity Score [NISS] ≥ 16); 541(9.3%) were transfused, 171(31.6%) in the first 4 h and 72(13.3%) using ≥3 units of products in the first hour. Firearms injuries were the most severe, most likely to be transfused urgently, using balanced resuscitation, and to die (p < 0.001 for all). Multivariable logistic regression showed any blood use as strongly associated with NISS (Odds Ratio 1.124832; p < 0.0001; 95% CI 1.11-1.13) but not with age (OR 0.98; p = 0.07; 95% CI 0.96-1.00). CONCLUSION: Transfusion in the care of acute paediatric trauma is uncommon (<10% of injured minors in our cohorts received any blood products), and injury severity, particularly firearms injury-not age-drove transfusion.

The transfusion service laboratory in virtual reality.

Due to the global SARS-CoV-2 pandemic, in-person laboratory medicine clerkships were converted to distance learning. The remote clerkship format provided advantages of allowing participation of students from more locations and greater scheduling flexibility but provided new challenges of maintaining learner engagement and providing experiential content of the laboratory environment. Gamification of educational content is one educational modality that has shown effectiveness in a multitude of different contexts to increase learner engagement and retention. Therefore, we created an interactive, educational 360° virtual reality walkthrough tour using off-the-shelf commercially available 360° cameras and software of the Transfusion service and Microbiology Laboratories. The process consists of taking multiple 360° still-images within the space, color-correction, blurring the faces of staff or sensitive information, adding navigation buttons, and other interactive elements. The virtual tours were used for both recruitment and education with further plans to integrate the learning modality into the curriculum. The clerkship is likely to remain as partially or fully as remote learning so such walkthrough tours will continue to remain relevant. This technology can be applied globally to other departments and institutions for education or recruitment.

Cold-stored whole blood and platelet counts in severe acute injury: A comparison of four retrospective cohorts.

BACKGROUND: Low-titer group O whole blood (LTOWB) is attractive for acute trauma care as it delivers concentrated and balanced hemostatic resuscitation in single large bags. Whether cold-stored LTOWB can sustain platelet counts is unclear. STUDY DESIGN AND METHODS: Four cohorts of trauma patients-three historic, one retrospective-were identified by their urgency of blood use. Admission and all subsequent platelet counts over the first 24 h of care were compared with t-tests. The cohorts were as follows: 1292 patients at Maryland Shock Trauma as described by Stansbury and colleagues in 2013; 35 patients enrolled locally in the 1:1:2 arm of the pragmatic randomized optimal plasma and platelet ratios (PROPPR) trial; 34 patients enrolled locally in the 1:1:1 arm of PROPPR; and 59 patients receiving more than 3 units of LTOWB enroute to or at our Level 1 trauma center, 2019-2020. RESULTS: Mean age of LTOWB units transfused was 9 ± 5 days and mean dose was 5 ± 2 units. All four cohorts were profoundly injured (mean Injury Severity Score ≥ 31), with mean first platelet counts 204-228 K/µ and subsequent counts approximately 100 k/µl lower. Through the first 24 h of care, mean platelet counts decreased least, 79 and 83 103 /µl, in the 1:1:1 PROPPR and LTOWB cohorts. Mean platelet counts in patients transfused with LTOWB remained stable after the third hour of care. DISCUSSION: LTOWB transfusion was associated with lesser mean decrease in platelet counts during the first 24 h after injury, similar to those observed among patients receiving components 1:1:1 component in the PROPPR study.

Rates of delayed hemolytic transfusion reactions observed in a trauma center.

BACKGROUND: Delayed hemolytic transfusion reactions (DHTRs) are reported to be rare occurrences but may be more frequently observed in the trauma setting where patients are heavily transfused, followed over long inpatient admissions, and have frequent subsequent blood counts as they undergo multiple surgical interventions. STUDY DESIGN AND METHODS: We examined the rates of DHTRs on a per transfusion and per patient basis in an academic county hospital with a level 1 trauma center serving a four-state region and over a 3-year period. DHTRs were entered sequentially into a registry as they were observed, and a retrospective review of all new alloantibodies detected was performed to identify any additional DHTRs. The number of units of red blood cells (RBCs), the number of unique patients, types of alloantibodies, and number of transfusions were extracted from blood bank records. RESULTS: Twenty-nine DHTRs were observed from January 1, 2017, through December 31, 2019, from newly observed alloantibodies after a median of 12 red blood cells (RBCs) transfusions per patient. These reactions occurred in response to 24,633 unique transfusions in 6905 unique patients, so the observed rates were about 1:849 RBC transfusions and 1:238 transfused patients. Evidence of delayed hemolysis was seen in five additional patients who were transfused during emergency resuscitation and later found to have had known RBC antibodies. DISCUSSION: We report a higher rate of DHTRs than previously described to demonstrate that DHTRs are not rare in trauma centers.

Benefits of lower neonatal platelet transfusion thresholds.

Degree of thrombocytopenia is not a predictor of bleeding risk in neonates, yet most platelet transfusions are given prophylactically in non-bleeding premature infants. Recent data support a lower platelet transfusion threshold of 25 × 109 /L in non-bleeding premature neonates and indicate that higher transfusion thresholds may be associated with harm including increased risk of death and bleeding. The mechanism of increased adverse events with higher platelet transfusion threshold is unknown, but considerations include adult platelets disrupting the neonatal hemostatic balance of hypoactive platelets in a hypercoagulable and fragile environment and having a pro-inflammatory effect.

Physical activity in children at risk of postthrombotic sequelae: a pilot randomized controlled trial.

Increased physical activity is protective against worsening of postthrombotic syndrome (PTS) in adults. We assessed patient eligibility, consent, adherence, and retention rates in a pilot trial of prescribed physical activity following venous thromboembolism (VTE) in children. Secondary objectives were to describe the within-subject changes in PTS, quality of life, and coagulation biomarkers before and after the intervention in each group. We enrolled and randomized patients between 7 and 21 years of age to the physical activity group or the standard care (education-only) group in a 1:1 allocation ratio. The physical activity group wore a Fitbit for 4 weeks to determine habitual activity and then increased activity over an 8-week "active" period, followed by a 4-week "do-as-you-wish" period. Two hundred thirty-five children were diagnosed with VTE; 111 patients were screened, of whom 40 (36%) met study eligibility criteria. Of these, 23 (57%) consented to participate and were randomized (Fitbit,11; standard group, 12). The trial was of greater interest to overweight and obese children, as they comprised 83% of consented patients. Only 33% adhered to the activity prescription, and 65% (15/23) completed the trial. The PTS scores (P = .001) improved in the physical activity group compared with the education-only group. It is feasible to enroll and randomize pediatric VTE patients to a prescribed physical activity regimen 3 months following VTE. Metrics for adherence to enhanced physical activity and retention were not met. These results provide the rationale to explore low adherence and retention rates before moving forward with a larger trial of exercise training following VTE. This trial was registered at www.clinicaltrials.gov as #NCT03075761.

The gut microbiome and thromboembolism.

The gut microbiome plays a critical role in various inflammatory conditions, and its modulation is a potential treatment option for these conditions. The role of the gut microbiome in the pathogenesis of thromboembolism has not been fully elucidated. In this review, we summarize the evidence linking the gut microbiome to the pathogenesis of arterial and venous thrombosis. In a human host, potentially pathogenic bacteria are normal residents of the human gut microbiome, but significantly outnumbered by commensal anaerobic bacteria. Several disease states with an increased risk of venous thromboembolism (VTE) are associated with an imbalance in the gut microbiome characterized by a decrease in commensal anaerobic bacteria and an increase in the abundance of pathogenic bacteria of which the most common is the gram-negative Enterobacteriaceae (ENTERO) family. Bacterial lipopolysaccharides (LPS), the glycolipids found on the outer membrane of gram-negative bacteria, is one of the links between the microbiome and hypercoagulability. LPS binds to toll-like receptors to activate endothelial cells and platelets, leading to activation of the coagulation cascade. Bacteria in the microbiome can also metabolite compounds in the diet to produce important metabolites like trimethylamine-N-oxide (TMAO). TMAO causes platelet hyperreactivity, promotes thrombus formation and is associated with cardiovascular disease. Modulating the gut microbiome to target LPS and TMAO levels may be an innovative approach for decreasing the risk of thrombosis.