Patient sex and outcomes in children with life-threatening hemorrhage.

BACKGROUND: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies. STUDY DESIGN AND METHODS: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses. RESULTS: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex. CONCLUSION: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age.

Epsilon aminocaproic acid is associated with acute kidney injury after life-threatening hemorrhage in children.

BACKGROUND: Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI). STUDY DESIGN AND METHODS: We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life-threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis. RESULTS: Of 448 children included, median (interquartile range) age was 7 (2-15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety-three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty-seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p = .002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre-LTH, and total weight-adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0-10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis. CONCLUSION: Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients.

Survey to inform trial of low-titer group O whole-blood compared to conventional blood components for children with severe traumatic bleeding.

BACKGROUND: Low-titer group O whole-blood (LTOWB) is being used for children with life-threatening traumatic bleeding. A survey was conducted to determine current LTOWB utilization and interest in participation in a randomized control trial (RCT) of LTOWB versus standard blood component transfusion in this population. STUDY DESIGN AND METHODS: Transfusion medicine (TM) directors and pediatric trauma directors at 36 US children's hospitals were surveyed by e-mail in June 2020. Hospitals were selected by participation in the Massive Transfusion Epidemiology and Outcomes in Children Study or being among the largest 30 children's hospitals by bed capacity per the Becker Hospital Review. RESULTS: The response rate was 83.3% (30/36) from TM directors and 88.9% (32/36) from trauma directors. The median of massive transfusion protocol activations for traumatic bleeding was reported as 12 (IQR 5.8-20) per year by TM directors. LTOWB was used by 18.8% (6/32) of trauma directors. Survey responses indicate that 86.7% (26/30) of TM directors and 90.6% (29/32) of trauma directors either moderately or strongly agree that a LTOWB RCT is important to perform. About 83.3% (25/30) of TM directors and 93.8% (30/32) of trauma directors were willing to participate in the proposed trial. About 80% (24/30) of TM directors and 71.9% (23/32) of trauma directors would transfuse RhD+ LTOWB to male children, but fewer would transfuse Rh + LTOWB to females [20% (6/30) TM directors and 37.5% (12/32) of trauma directors]. CONCLUSIONS: A majority of respondents supported an RCT comparing LTOWB to component therapy in children with severe traumatic bleeding.