Background Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. Methods In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d -dimer level. Results The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d -dimer cohort, 92.9% in the low d -dimer cohort, and 97.3% in the unknown d -dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. Conclusions In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589 , NCT04505774 , NCT04359277 , and NCT02735707 .)

No transfusion reactions were reported. The median (IQR) time from ED admission to the start of the WB transfusion was 15 (14-77) minutes, compared with 303 (129-741) minutes (P < .001) for administration of at least 1 unit of RBCs, plasma, and platelets in the historical cohort (Figure).Discussion | To our knowledge, this is the first cohort of pediatric civilian trauma patients to receive WB during resuscitation. These preliminary data suggest that WB transfusion of up to 20 mL/kg is safe in children with severe injuries; there was no evidence of hemolysis in non-group O recipients, and no transfusion reactions were reported. Based on these data, the transfusion committee of Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center approved an increase in maximum volume of WB transfusion to 30 mL/kg. Larger cohorts are necessary for further study to determine if WB administration will affect outcomes, including number of donor exposures, cost, total volume transfused, and mortality.

Background The Injury Severity Score (ISS) is the most commonly used injury scoring system in trauma research and benchmarking. An ISS>15 conventionally defines severe injury; however, no studies evaluate whether ISS performs similarly between adults and children. Our objective was to evaluate ISS and AIS to predict mortality and define optimal thresholds of severe injury in pediatric trauma. Methods Patients from the Pennsylvania trauma registry 2000–2013 were included. Children were defined as age<16years. Logistic regression predicted mortality from ISS for children and adults. The optimal ISS cut-off for mortality that maximized diagnostic characteristics was determined in children. Regression also evaluated association between mortality and maximum AIS in each body-region, controlling for age, mechanism, and non-accidental trauma. Analysis was performed in single and multisystem injuries. Sensitivity analyses with alternative outcomes were performed. Results There were 352,127 adults and 50,579 children included. Children had similar predicted mortality at ISS of 25 as adults at ISS of 15 (5%). The optimal ISS cut-off in children was ISS>25 and had a positive predictive value (PPV) of 19% and negative predictive value (NPV) of 99% compared to PPV of 7% and NPV of 99% for ISS>15 to predict mortality. In single-system injured children, mortality was associated with head (OR 4.80; 95%CI 2.61–8.84, p<0.01) and chest AIS (OR 3.55; 95%CI 1.81–6.97, p<0.01), but not abdomen, face, neck, spine, or extremity AIS (p>0.05). For multisystem injury, all body region AIS were associated with mortality except extremities. Sensitivity analysis demonstrated ISS>23 to predict need for full trauma activation, and ISS>26 to predict impaired functional independence were optimal. Conclusions ISS>25 may be a more appropriate definition of severe injury in children. Pattern of injury is important, as only head and chest injury drive mortality in single-system injured children. These findings should be considered in benchmarking and performance improvement efforts. Level of Evidence III, epidemiologic

Objective: To compare a propensity-matched cohort of injured children receiving conventional blood component transfusion to injured children receiving low-titer group O negative whole blood. Summary of Background Data: Transfusion of whole blood in pediatric trauma patients is feasible and safe. Effectiveness has not been evaluated. Methods: Injured children ≥1 years old can receive up to 40 mL/kg of cold-stored, uncrossmatched whole blood during initial hemostatic resuscitation. Whole blood recipients (2016–2019) were compared to a propensity-matched cohort who received at least 1 uncrossmatched red blood cell unit in the trauma bay (2013–2016). Cohorts were matched for age, hypotension, traumatic brain injury, injury mechanism, and need for emergent surgery. Outcomes included time to resolution of base deficit, product volumes transfused, and INR after resuscitation. Results: Twenty-eight children who received whole blood were matched to 28 children who received components. The whole blood group had faster time to resolution of base deficit [median (IQR) 2 (1–2.5) hours vs 6 (2–24) hours, respectively; P < 0.001]. The post-transfusion INR was decreased in whole blood vs component cohort [median (IQR) 1.4 (1.3–1.5) vs 1.6 (1.4–2.2); P = 0.01]. Lower plasma volumes [median (IQR) = 5 (0–15) mL/kg vs 11 (5–35) mL/kg; P = 0.04] and lower platelet volumes [median (IQR) = 0 (0–2) vs 3 (0–8); P = 0.03] were administered to the whole blood group versus component group. Other clinical variables (in-hospital death, hospital length of stay, intensive care unit length of stay, and ventilator days) did not differ between groups. Conclusions: Compared to component transfusion, whole blood transfusion results in faster resolution of shock, lower post-transfusion INR, and decreased component product transfusion. Larger cohorts are required to support these findings.

Prognostic and epidemiologic study, level III.

TBI therapy is closely linked to the development of DVT. Coagulopathy on admission is associated with hypercoagulability in the postinjury period, suggesting a patient phenotype with systemic coagulation dysregulation. Treatment was not associated with improved VTE outcomes, suggesting that pediatric protocols should emphasize VTE prevention and prophylaxis strategies.

Objective: The aim of this study was to assess the survival impact of low-titer group O whole blood (LTOWB) in injured pediatric patients who require massive transfusion. Summary Background Data: Limited data are available regarding the effectiveness of LTOWB in pediatric trauma. Methods: A prospective observational study of children requiring massive transfusion after injury at UPMC Children’s Hospital of Pittsburgh, an urban academic pediatric Level 1 trauma center. Injured children ages 1 to 17 years who received a total of >40 mL/kg of LTOWB and/or conventional components over the 24 hours after admission were included. Patient characteristics, blood product utilization and clinical outcomes were analyzed using Kaplan-Meier survival curves, log rank tests and Cox proportional hazards regression analyses. The primary outcome was 28-day survival. Results: Of patients analyzed, 27 of 80 (33%) received LTOWB as part of their hemostatic resuscitation. The LTOWB group was comparable to the component therapy group on baseline demographic and physiologic parameters except older age, higher body weight, and lower red blood cell and plasma transfusion volumes. After adjusting for age, total blood product volume transfused in 24 hours, admission base deficit, international normalized ratio (INR), and injury severity score (ISS), children who received LTOWB as part of their resuscitation had significantly improved survival at both 72 hours and 28 days post-trauma [adjusted odds ratio (AOR) 0.23, P = 0.009 and AOR 0.41, P = 0.02, respectively]; 6-hour survival was not statistically significant (AOR = 0.51, P = 0.30). Survivors at 28 days in the LTOWB group had reduced hospital LOS, ICU LOS, and ventilator days compared to the CT group. Conclusion: Administration of LTOWB during the hemostatic resuscitation of injured children requiring massive transfusion was independently associated with improved 72-hour and 28-day survival.

Despite over a half-century of recognizing fibrinolytic abnormalities after trauma, we remain in our infancy in understanding the underlying mechanisms causing these changes, resulting in ineffective treatment strategies. With the increased utilization of viscoelastic hemostatic assays (VHAs) to measure fibrinolysis in trauma, more questions than answers are emerging. Although it seems certain that low fibrinolytic activity measured by VHA is common after injury and associated with increased mortality, we now recognize subphenotypes within this population and that specific cohorts arise depending on the specific time from injury when samples are collected. Future studies should focus on these subtleties and distinctions, as hypofibrinolysis, acute shutdown, and persistent shutdown appear to represent distinct, unique clinical phenotypes, with different pathophysiology, and warranting different treatment strategies.