RESUMO
BACKGROUND: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.
RESUMO
BACKGROUND: Heparin administration can induce the production of anti-platelet factor 4 (PF4)/heparin antibodies with platelet-activating properties, causing heparin-induced thrombocytopenia (HIT). Previous studies have suggested that trauma severity influences HIT immune responses, but their relationship has not been fully explained. This study aimed to clarify this association by multicenter prospective observational study. METHODS: Trauma patients who met the criteria of age 18 years or older and Injury Severity Scores (ISSs) of ≥9 from March 2018 to February 2019 were included. Patients who did not receive any heparin and those who received it as flushes or for treatment were also included. Patients were divided into three groups based on trauma severity (to mild [ISS 9-15], moderate [ISS 16-24], and severe injury groups [ISS ≥25]) and were compared by the seroconversion time and rate, as well as the disappearance rate of antibodies on day 30. RESULTS: A total of 184 patients were included: 55, 62, and 67 patients were classified into the mild, moderate, and severe injury groups, respectively. Overall, the seroconversion rates of anti-PF4/heparin immunoglobulin G (IgG) and HIT antibodies by washed platelet activation assay were 26.6% and 16.3%, respectively. There was a significant difference in the seroconversion rates of anti-PF4/heparin IgG ( p = 0.016) and HIT antibodies ( p = 0.046) among the groups. Seroconversion rates in both assays increased with increasing trauma severity. The time required to achieve seroconversion was similar (between 5 and 10 days of trauma onset) regardless of heparin administration. Anti-PF4/heparin IgG and HIT antibodies were no longer detected on day 30 in 28.6% and 60.9% of seroconverted patients, respectively. CONCLUSION: Development of HIT antibodies was observed commonly in severely injured trauma patients. Heparin-induced thrombocytopenia antibody development may be related to trauma severity, with a high disappearance frequency on day 30. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.