Abstract

IMPORTANCE Tranexamic acid is widely available and used off-label in patients with bleeding traumatic injury, although the literature does not consistently agree on its efficacy and safety. OBJECTIVE To examine the association of tranexamic acid administration with mortality and thromboembolic events compared with no treatment or with placebo in patients with traumatic injury in the literature. DATA SOURCES On March 23, 2021, PubMed, Embase, and the Cochrane Library were searched for eligible studies published between 1986 and 2021. STUDY SELECTION Randomized clinical trials and observational studies investigating tranexamic acid administration compared with no treatment or placebo among patients with traumatic injury and traumatic brain injury who were 15 years or older were included. Included studies were published in English or German. The electronic search yielded 1546 records, of which 71 were considered for full-text screening. The selection process was performed independently by 2 reviewers. DATA EXTRACTION AND SYNTHESIS The study followed the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 2 independent reviewers and pooled using the inverse-variance random-effects model. MAIN OUTCOMES AND MEASURES Outcomes were formulated before data collection and included mortality at 24 hours and 28 and 30 days (1 month) as well as the incidence of thromboembolic events and the amount of blood products administered. Owing to missing data, overall mortality was added and the amount of blood products administered was discarded. RESULTS Thirty-one studies with a total of 43 473 patients were included in the systematic review. The meta-analysis demonstrated that administration of tranexamic acid was associated with a significant decrease in 1-month mortality compared with the control cohort (risk ratio, 0.83 [95% CI, 0.71-0.97]; I2 = 35%). The results of meta-analyses for 24-hour and overall mortality and thromboembolic events were heterogeneous and could not be pooled. Further investigations on clinical heterogeneity showed that populations with trauma and trial conditions differed markedly. CONCLUSIONS AND RELEVANCE These findings suggest that tranexamic acid may be beneficial in various patient populations with trauma. However, reasonable concerns about potential thromboembolic events with tranexamic acid remain.

Abstract

Severely injured trauma patients are often coagulopathic and early hemostatic resuscitation is essential. Previous studies have revealed linear relationships between thrombelastography (TEG(®)) five- and ten-min amplitudes (A5 and A10), and maximum amplitude (MA), using TEG(®) 5000 technology. We aimed to investigate the performance of A5 and A10 in predicting low MA in severely injured trauma patients and identify optimal cut-off values for hemostatic intervention based on early amplitudes, using the cartridge-based TEG(®) 6s technology. Adult trauma patients with hemorrhagic shock were included in the iTACTIC randomized controlled trial at six European Level I trauma centers between 2016 and 2018. After admission, patients were randomized to hemostatic therapy guided by conventional coagulation tests (CCT) or viscoelastic hemostatic assays (VHA). Patients with available admission-TEG(®) 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG(®) and RapidTEG(®), and <17 mm for TEG(®) functional fibrinogen (FF). One hundred eighty-seven patients were included. Median time to MA was 20 (Kaolin TEG(®)), 21 (RapidTEG(®)) and 12 (TEG(®) FF) min. For Kaolin TEG(®), the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG(®) optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG(®) FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity). In summary, we found that TEG(®) 6s early amplitudes were sensitive and specific predictors of MA in severely injured trauma patients. Intervening on early amplitudes can save valuable time in hemostatic resuscitation.

Abstract

PURPOSE Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Abstract

BACKGROUND Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients. OBJECTIVE The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed. DESIGN A prospective, randomised, placebo-controlled, double-blinded, international clinical trial. SETTING This emergency care trial was conducted in 12 Helicopter Emergency Medical Services (HEMS) and Emergency Doctors' vehicles (NEF or NAW) and four trauma centres in Austria, Germany and Czech Republic between 2011 and 2015. PATIENTS A total of 53 evaluable trauma patients aged at least 18 years with major bleeding and in need of volume therapy were included, of whom 28 received fibrinogen concentrate and 25 received placebo. INTERVENTIONS Patients were allocated to receive either fibrinogen concentrate or placebo prehospital at the scene or during transportation to the study centre. MAIN OUTCOME MEASURES Primary outcome was the assessment of clot stability as reflected by maximum clot firmness in the FIBTEM assay (FIBTEM MCF) before and after administration of the study drug. RESULTS Median FIBTEM MCF decreased in the placebo group between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5 [IQR 10.5 to 14] mm to 11 [9.5 to 13] mm (P = 0.0226), but increased in the FC Group from 13 [11 to 15] mm to 15 [13.5 to 17] mm (P = 0.0062). The median between-group difference in the change in FIBTEM MCF was 5 [3 to 7] mm (P < 0.0001). Median fibrinogen plasma concentrations in the fibrinogen concentrate Group were kept above the recommended critical threshold of 2.0 g l throughout the observation period. CONCLUSION Early fibrinogen concentrate administration is feasible in the complex and time-sensitive environment of prehospital trauma care. It protects against early fibrinogen depletion, and promotes rapid blood clot initiation and clot stability. TRIAL REGISTRY NUMBERS EudraCT: 2010-022923-31 and ClinicalTrials.gov: NCT01475344.

Abstract

BACKGROUND Uncontrolled bleeding with trauma-induced coagulopathy (TIC) is still the most common avoidable cause of death in multiple trauma. The aging of the population has led to an increasing number of bleeding trauma patients with pre-existing anticoagulation. Such patients are not treated uniformly, even in major trauma centers. METHODS This review is based on a selective search of the literature (Medline/PubMed, Cochrane Reviews) and summarizes current treatment recommendations, including those of the newly revised European trauma guidelines. RESULTS The treatment of traumatic hemorrhage begins at the site of the accident, with compression, tourniquets, pelvic binders, and rapid transport to a certified trauma center. The early use of tourniquets was shown to lessen the trans- fusion requirement (packed red blood cells: 2.0 +/- 0.1 vs. 9.3 +/- 0.6; p < 0.001; fresh frozen plasma concentrates: 1.4 +/- 0.08 vs. 6.2 +/- 0.4; p < 0.001), while external pelvic stabilization was shown to reduce mortality (19.1% vs. 33.3%). Upon the patient's arrival in the hospital, steps are taken to measure, monitor, and support clotting function. Bleeding is controlled surgically according to the principles of damage control. Modern clotting management consists of goal-oriented, individualized therapy, including the use of point-of-care viscoelastic test procedures. Idarucizumab can be used as an antidote to the thrombin inhibitor dabigatran, andexanet alpha as an antidote to factor Xa inhibitors. CONCLUSION The evidence-based treatment of patients with hemorrhage from severe trauma, in accordance with the existing guidelines, can improve the clinical outcome. Corresponding algorithms, adapted to local logistics and infrastructure, must be developed and implemented.