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Sex-based differences in transfusion need after severe injury: Findings of the PROPPR study.

ABSTRACT: BACKGROUND:Women are underrepresented in trauma research, and aggregated results of clinical trials may mask effects that differ by sex. It is unclear whether women respond differently to severe hemorrhage compared with men. We sought to evaluate sex-based differences in outcomes after severe trauma with hemorrhage. METHODS:We performed a secondary analysis of the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial. Trauma patients predicted to require massive transfusion were randomized to a 1:1:1 vs 1:1:2 plasma to platelet to red blood cell transfusion ratio. Analysis was performed according to sex, controlling for clinical characteristics and transfusion arm. RESULTS:A total of 134 women and 546 men were analyzed. In multivariable analysis, there was no difference in mortality at 24 hours (hazard ratio for women 0.64, 95% confidence interval 0.34-1.23, P = .18) or in time to hemostasis (hazard ratio 1.10, 95% confidence interval 0.84-1.42, P = .49) by sex. We observed no difference between sexes in volume of blood products transfused during active hemorrhage. However, after anatomic hemostasis, women received lower volumes of all products, with a 38% reduction in fresh frozen plasma (mean ratio 0.62 (95% confidence interval 0.43-0.89, P = .01), 49% reduction in platelets (mean ratio 0.51, 95% confidence interval 0.33-0.79, P < .01) and 49% reduction in volume of red blood cells (mean ratio 0.51, 95% confidence interval 0.33-0.79, P < .01). CONCLUSION:Mortality and time to hemostasis of trauma patients with hemorrhage did not differ by sex. Although there was no difference in transfusion requirement during active hemorrhage, once hemostasis was achieved, women received fewer units of all blood products than men. Further research is required to determine whether women exhibit differences in coagulation during and after severe traumatic hemorrhage.

SUBMITTER: McCrum ML

PROVIDER: S-EPMC6581613 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Sex-based differences in transfusion need after severe injury: Findings of the PROPPR study.

McCrum Marta L ML Leroux Brian B Fang Tingzhi T Bulger Eileen E Arbabi Sam S Wade Charles E CE Fox Erin E Holcomb John B JB Robinson Bryce B

Surgery 20190312 6

<h4>Background</h4>Women are underrepresented in trauma research, and aggregated results of clinical trials may mask effects that differ by sex. It is unclear whether women respond differently to severe hemorrhage compared with men. We sought to evaluate sex-based differences in outcomes after severe trauma with hemorrhage.<h4>Methods</h4>We performed a secondary analysis of the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial. Trauma patients predicted to require massive transfusio ...[more]

PMID: 30871812

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Project description:The effect of sex on posttraumatic pathophysiology and outcomes after severe traumatic injury remains debated. We sought to determine the relationship of sex to the genomic and inflammatory responses, and clinical outcomes after hemorrhagic shock.We analyzed blunt trauma patients in hemorrhagic shock from a prospective multi-institutional cohort study to assess for sex-based differences in the genomic response and clinical outcomes. Serially drawn blood samples were analyzed to evaluate peripheral leukocyte genomewide expression and circulating inflammatory mediators at intervals between 0.5 and 28 days after injury. Multivariate logistic regression models were developed to assess the effect of sex on outcomes after controlling for age, injury and shock severity, blood transfusion, and comorbidities.The cohort consisted of 1,285 (67%) male and 643 (33%) female blunt trauma patients. Injury and shock severity were similar between the two groups. There were small but statistically significant differences between males and females regarding their age, body mass index, and 12-hour blood and crystalloid administration. Organ failure was more severe in males, with slower recovery (9.0 vs. 6.5 days) in males compared to females (p < 0.01). However, there were no differences between males and females in plasma levels of IL-6, IL-8, IL-10, IL-1?, tumor necrosis factor alpha, and monocyte chemoattractant protein 1. Multivariate analysis revealed that sex was not a significant independent risk factor for complicated recovery or 28-day mortality. Transcriptomic analysis revealed 333 genes with significant differential expression patterns between males and females (FDR, <0.001), including genes associated with general inflammation, innate immunity, cell adhesion, and cell signaling. None of the former genes were directly associated with sex hormones or X/Y chromosomes.There are sex-specific differences in the leukocyte genomic response to severe injury that are associated with more robust and longer-duration organ dysfunction. However, these expression patterns do not seem to be associated with sex-linked genes or circulating cytokine level differences, and do not translate to worsened sex-specific organ failure outcomes or inpatient mortality.Prognostic/epidemiologic study, level III.

Project description:OBJECT There is limited literature available to guide transfusion practices for patients with severe traumatic brain injury (TBI). Recent studies have shown that maintaining a higher hemoglobin threshold after severe TBI offers no clinical benefit. The present study aimed to determine if a higher transfusion threshold was independently associated with an increased risk of progressive hemorrhagic injury (PHI), thereby contributing to higher rates of morbidity and mortality. METHODS The authors performed a secondary analysis of data obtained from a recently performed randomized clinical trial studying the effects of erythropoietin and blood transfusions on neurological recovery after severe TBI. Assigned hemoglobin thresholds (10 g/dl vs 7 g/dl) were maintained with packed red blood cell transfusions during the acute phase after injury. PHI was defined as the presence of new or enlarging intracranial hematomas on CT as long as 10 days after injury. A severe PHI was defined as an event that required an escalation of medical management or surgical intervention. Clinical and imaging parameters and transfusion thresholds were used in a multivariate Cox regression analysis to identify independent risk factors for PHI. RESULTS Among 200 patients enrolled in the trial, PHI was detected in 61 patients (30.5%). The majority of patients with PHI had a new, delayed contusion (n = 29) or an increase in contusion size (n = 15). The mean time interval between injury and identification of PHI was 17.2 ± 15.8 hours. The adjusted risk of severe PHI was 2.3 times higher for patients with a transfusion threshold of 10 g/dl (95% confidence interval 1.1-4.7; p = 0.02). Diffuse brain injury was associated with a lower risk of PHI events, whereas higher initial intracranial pressure increased the risk of PHI (p < 0.001). PHI was associated with a longer median length of stay in the intensive care unit (18.3 vs 14.4 days, respectively; p = 0.04) and poorer Glasgow Outcome Scale scores (42.9% vs 25.5%, respectively; p = 0.02) at 6 months. CONCLUSIONS A higher transfusion threshold of 10 g/dl after severe TBI increased the risk of severe PHI events. These results indicate the potential adverse effect of using a higher hemoglobin transfusion threshold after severe TBI.

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Sex-based differences in transfusion need after severe injury: Findings of the PROPPR study.

Publications

Sex-based differences in transfusion need after severe injury: Findings of the PROPPR study.

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