Severely injured trauma patients with admission hyperfibrinolysis: Is there a role of tranexamic acid? Findings from the PROPPR trial

Khan, Muhammad; Jehan, Faisal; Bulger, Eileen M.; OʼKeeffe, Terence; Holcomb, John B.; Wade, Charles E.; Schreiber, Martin A.; Joseph, Bellal

doi:10.1097/ta.0000000000002022

Cited by 32 publications

(18 citation statements)

References 26 publications

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“…However, this study did not address patients presenting with other fibrinolytic phenotypes. [ 13 ] The finding from our study was contrary to our prediction that hypofibrinolytic patients would experience higher rates of mortality considering the added effects of intrinsic delayed clot lysis and TXA mechanistically further delaying clot lysis.…”

Section: Discussioncontrasting

confidence: 99%

Safety and efficacy of thromboelastography guidance of antifibrinolytic therapy in trauma patients: An observational cohort analysis

Heilbronner

Kincaid

Walliser

et al. 2021

Int J Crit Illn Inj Sci

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Background: Tranexamic acid (TXA) is an antifibrinolytic therapy intended to decrease blood loss and improve hemostasis in traumatic hemorrhage. Viscoelastic assays, such as thromboelastography (TEG), allow for the identification of a patient's specific hemostasis. The purpose of this research study was to explore the safety and efficacy of TEG-guided antifibrinolytic therapy in trauma patients. Methods: This study was a retrospective review of trauma patients meeting institution-specific inclusion criteria for TXA. Patients were assigned to fibrinolytic groups per TEG LY30 data. Safety outcomes (24-h mortality, overall in-hospital mortality, and thromboembolic events) were compared between patients who did or did not receive TXA and within fibrinolytic groups. Mortality outcomes were adjusted for baseline Injury Severity Score (ISS). Secondary aims included blood product utilization, length of hospital, and intensive care unit stay. Results: Hypofibrinolysis was the most common fibrinolytic phenotype. Adjusting for ISS, there were no significant differences in mortality. A 30.7% thromboembolism incidence was identified in the TXA group compared to 16.6% not receiving TXA ( P = 0.26), with 72.7% of these patients experiencing fibrinolytic shutdown. Conclusions: There were no differences in 24-h mortality, all-cause mortality, or secondary outcomes. The difference in thromboembolic rates between patients receiving TXA and those who did not, while not statistically significant, poses clinical concern.

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Section: Discussioncontrasting

confidence: 99%

Safety and efficacy of thromboelastography guidance of antifibrinolytic therapy in trauma patients: An observational cohort analysis

Heilbronner

Kincaid

Walliser

et al. 2021

Int J Crit Illn Inj Sci

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“…Twelve studies 3,14,19,[21][22][23][24][25]30,32,33,37 revealed higher and 8 studies 2,4,13,18,20,28,36,39 revealed lower incidences of thromboembolic events for tranexamic acid treatment compared with the control cohort. Three studies 26,34,35 could not find any association (RR, 1.00) between tranexamic acid administration and thromboembolic events. It was not possible to resolve heterogeneity through the analysis of RCTs only (I 2 = 59%; P = .03).…”

Section: Association Between Tranexamic Acid and Thromboembolic Event...mentioning

confidence: 92%

“…Twenty-one studies [2][3][4]13,15,16,[20][21][22][24][25][26]28,[30][31][32][34][35][36][37]39 had reported lower mortality and 9 studies 14,17,19,23,27,29,33,38,40…”

Section: Meta-analysis Of 24-hour Mortality Datamentioning

confidence: 99%

Association of Tranexamic Acid Administration With Mortality and Thromboembolic Events in Patients With Traumatic Injury

et al. 2022

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IMPORTANCETranexamic 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 MEASURESOutcomes 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. RESULTSThirty-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]; I 2 = 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 RELEVANCEThese 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.

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“…Added plasmin identifies patients at highest risk for hyperfibrinolysis within 5 min instead of 60 min, and therefore may prove useful for selective and timely administration of TXA [ 175 ]. The detection of hyperfibrinolysis can direct selective use of TXA [ 176 ] rather than empiric treatment of all trauma patients with this potentially dangerous anti-fibrinolytic. Until recently, VEAs results and the reproducibility of results were dependent on the accuracy of pipetting while performing the assay.…”

Section: Management Of the Polytrauma Victimmentioning

confidence: 99%

The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient

Fecher

Stimpson

Ferrigno

et al. 2021

JCM

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The recognition and management of life-threatening hemorrhage in the polytrauma patient poses several challenges to prehospital rescue personnel and hospital providers. First, identification of acute blood loss and the magnitude of lost volume after torso injury may not be readily apparent in the field. Because of the expression of highly effective physiological mechanisms that compensate for a sudden decrease in circulatory volume, a polytrauma patient with a significant blood loss may appear normal during examination by first responders. Consequently, for every polytrauma victim with a significant mechanism of injury we assume substantial blood loss has occurred and life-threatening hemorrhage is progressing until we can prove the contrary. Second, a decision to begin damage control resuscitation (DCR), a costly, highly complex, and potentially dangerous intervention must often be reached with little time and without sufficient clinical information about the intended recipient. Whether to begin DCR in the prehospital phase remains controversial. Furthermore, DCR executed imperfectly has the potential to worsen serious derangements including acidosis, coagulopathy, and profound homeostatic imbalances that DCR is designed to correct. Additionally, transfusion of large amounts of homologous blood during DCR potentially disrupts immune and inflammatory systems, which may induce severe systemic autoinflammatory disease in the aftermath of DCR. Third, controversy remains over the composition of components that are transfused during DCR. For practical reasons, unmatched liquid plasma or freeze-dried plasma is transfused now more commonly than ABO-matched fresh frozen plasma. Low-titer type O whole blood may prove safer than red cell components, although maintaining an inventory of whole blood for possible massive transfusion during DCR creates significant challenges for blood banks. Lastly, as the primary principle of management of life-threatening hemorrhage is surgical or angiographic control of bleeding, DCR must not eclipse these definitive interventions.

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Severely injured trauma patients with admission hyperfibrinolysis: Is there a role of tranexamic acid? Findings from the PROPPR trial

Abstract: Therapeutic study, level III.

Cited by 32 publications

References 26 publications

Safety and efficacy of thromboelastography guidance of antifibrinolytic therapy in trauma patients: An observational cohort analysis

Safety and efficacy of thromboelastography guidance of antifibrinolytic therapy in trauma patients: An observational cohort analysis

Association of Tranexamic Acid Administration With Mortality and Thromboembolic Events in Patients With Traumatic Injury

The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient

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