Impact of COVID status and blood group on complications in patients in hemorrhagic shock.

Objective: Among critically injured patients of various blood groups, we sought to compare survival and complication rates between COVID-19-positive and COVID-19-negative cohorts. Background: SARS-CoV-2 infections have been shown to cause endothelial injury and dysfunctional coagulation. We hypothesized that, among patients with trauma in hemorrhagic shock, COVID-19-positive status would be associated with increased mortality and inpatient complications. As a secondary hypothesis, we suspected group O patients with COVID-19 would experience fewer complications than non-group O patients with COVID-19. Methods: We evaluated all trauma patients admitted 4/2020-7/2020. Patients 16 years or older were included if they presented in hemorrhagic shock and received emergency release blood products. Patients were dichotomized by COVID-19 testing and then divided by blood groups. Results: 3281 patients with trauma were evaluated, and 417 met criteria for analysis. Seven percent (29) of patients were COVID-19 positive; 388 were COVID-19 negative. COVID-19-positive patients experienced higher complication rates than the COVID-19-negative cohort, including acute kidney injury, pneumonia, sepsis, venous thromboembolism, and systemic inflammatory response syndrome. Univariate analysis by blood groups demonstrated that survival for COVID-19-positive group O patients was similar to that of COVID-19-negative patients (79 vs 78%). However, COVID-19-positive non-group O patients had a significantly lower survival (38%). Controlling for age, sex and Injury Severity Score, COVID-19-positive patients had a greater than 70% decreased odds of survival (OR 0.28, 95% CI 0.09 to 0.81; p=0.019). Conclusions: COVID-19 status is associated with increased major complications and 70% decreased odds of survival in this group of patients with trauma. However, among patients with COVID-19, blood group O was associated with twofold increased survival over other blood groups. This survival rate was similar to that of patients without COVID-19.

Fibrinogen Fragment X Mediates Endothelial Barrier Disruption via Suppression of VE-Cadherin.

INTRODUCTION: Major traumatic injury is associated with early hemorrhage-related and late-stage deaths due to multiple organ failure (MOF). While improvements to hemostatic resuscitation have significantly reduced hemorrhage-related deaths, the incidence of MOF among trauma patients remains high. Dysregulation of vascular endothelial cell (EC) barrier function is a central mechanism in the development of MOF; however, the mechanistic triggers remain unknown. Accelerated fibrinolysis occurs in a majority of trauma patients, resulting in high circulating levels of fibrin(ogen) degradation products, such as fragment X. To date, the relationship between fragment X and EC dysregulation and barrier disruption is unknown. The goal of this study was to determine the effects of fragment X on EC barrier integrity and expression of paracellular junctional proteins that regulate barrier function. METHODS: Human lung microvascular endothelial cells (HLMVECs) were treated with increasing concentrations of fragment X (1, 10, and 100 µg/mL), and barrier function was monitored using the xCELLigence live-cell monitoring system. Quantitative PCR (qPCR) was performed to measure changes in EC expression of 84 genes. Immunofluorescent (IF) cytostaining was performed to validate qPCR findings. RESULTS: Fragment X treatment significantly increased endothelial permeability over time (P < 0.05). There was also a significant reduction in VE-cadherin mRNA expression in fragment X-treated HLMVECs compared to control (P = 0.01), which was confirmed by IF staining. CONCLUSIONS: Fragment X may induce EC hyperpermeability by reducing VE-cadherin expression. This suggests that a targeted approach to disrupting EC-fragment X interactions could mitigate EC barrier disruption, organ edema, and MOF associated with major trauma.

Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury.

The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure following traumatic brain injury (TBI). We assessed the influence of these genotypes on clinical outcomes and ICP in TBI patients. We included 292 trauma patients with TBI. DNA extraction and real-time PCR were used for TRPM4 rs8104571 and rs150391806 allele discrimination. Five participants were determined to have the rs8104571 homozygous variant genotype, and 20 participants were identified as heterozygotes; 24 of these 25 participants were African American. No participants had rs150391806 variant alleles, preventing further analysis of this SNP. Genotypes containing the rs8104571 variant allele were associated with decreased Glasgow outcome scale-extended (GOSE) score (P = 0.0231), which was also consistent within our African-American subpopulation (P = 0.0324). Regression analysis identified an association between rs8104571 variant homozygotes and mortality within our overall population (P = 0.0230) and among African Americans (P = 0.0244). Participants with rs8104571 variant genotypes exhibited an overall increase in ICP (P = 0.0077), although a greater frequency of ICP measurements > 25 mmHg was observed in wild-type participants (P = < 0.0001). We report an association between the TRPM4 rs8104571 variant allele and poor outcomes following TBI. These findings can potentially be translated into a precision medicine approach for African Americans following TBI utilizing TRPM4-specific pharmaceutical interventions. Validation through larger cohorts is warranted.

Is Low-Titer Group O Whole Blood Truly a Universal Blood Product?

BACKGROUND: Whole blood was historically transfused as a type-specific product. Given recent advocacy for low-titer group O whole blood (LTOWB) as a universal blood product, we examined outcomes after LTOWB transfusion stratified by recipient blood groups. STUDY DESIGN: Adult trauma patients receiving prehospital or in-hospital transfusion of LTOWB (November 2017 to July 2020) at a single trauma center were prospectively evaluated. The patients were divided into blood type groups (O, A, B, and AB). Major complications and survival to 30 days were compared. Univariate analyses among blood groups were followed by purposeful regression modeling, reflecting 6 variables of significance: male sex, White race, injury severity, arrival lactate, arrival systolic blood pressure, and emergency department blood products. RESULTS: Of 1,075 patients receiving any LTOWB, 539 (50.1%) were Group O, 340 (31.6%) were Group A, 150 (14.0%) were Group B, and 46 (4.3%) were Group AB. There were no statistically significant differences in demographics, injury severity, hemolysis panels, prehospital vitals, or resuscitation parameters (all p > 0.05). However, arrival systolic pressure was lower (91 vs 102, p = 0.034) and lactate was worse (5.5 vs 4.1, p = 0.048) in Group B patients compared to other groups. While survival and most major complications did not differ across recipient groups, acute kidney injury (AKI) initially appeared higher for Group B. Stepwise regression did not show a difference in AKI rates. This analysis was repeated in patients receiving only component products. Group B again showed no significantly increased risk of AKI (13%) compared to other groups (O 7%, A 7%, AB 5%; p = 0.091). CONCLUSIONS: LTOWB appears to be a safe product for universal use across all blood groups. Group B recipients arrived with worse physiologic values associated with hemorrhagic shock whether receiving LTOWB or standard component products.

Can RH+ whole blood be safely used as an alternative to RH- product? An analysis of efforts to improve the sustainability of a hospital's low titer group O whole blood program.

BACKGROUND: Low-titer group O whole blood (LTO-WB) has recently gained popularity in trauma centers for the acute resuscitation of hemorrhagic shock. However, limited supplies of Rh- product prevent implementation and strain sustainability at many trauma centers. We set out to identify whether Rh+ LTO-WB could be safely substituted for RH- product, regardless of patient's Rh status. METHODS: Following Institutional Review Board approval, information on all trauma patients receiving prehospital or emergency department transfusion of uncrossed, emergency release LTO-WB (11/17-10/19) were evaluated. Patients were first divided into those who received Rh- versus Rh+ product, the assessed by Rh of the recipient. Serial hemolysis panels, transfusion reactions, and outcomes were compared. RESULTS: Six hundred thirty-seven consecutive trauma patients received emergency release LTO-WB. Of these, 448 received Rh+ product, while 189 received Rh- LTO-WB. Patients receiving Rh+ product were more likely to be men (81 vs. 70%) and have lower field blood pressure (median 99 vs. 109) and GCS (median 7 vs. 12); all p < 0.05. There were no differences in blood product volume, hemolysis laboratories, transfusion reactions, complications, or survival. We then separated patients by Rh status (577 were Rh+, 70 were Rh-). Rh- patients were older (median age 54 vs. 39), more likely to be women (57 vs. 26%), and more likely to have sustained blunt trauma than their Rh+ counterparts (92 vs. 70%); all p < 0.05. There were no differences in hemolysis laboratories, transfusion reactions, complications, or survival between Rh+ and Rh- patients, regardless of Rh product received. CONCLUSION: When Rh- whole blood is unavailable or in short supply, Rh+ LTO-WB appears to be a safe alternative for the resuscitation of hemorrhagic shock in both Rh+ and Rh- patients. Use of Rh+ product may help trauma centers incorporate LTO-WB into their hospital and improve sustainability of such programs. LEVEL OF EVIDENCE: Therapeutic, Level III.