Adravanti P, Di Salvo E, Calafiore G, Vasta S, Ampollini A, Rosa MA
Arthroplast Today. 2017 Oct 6;4(1):85-88
Background: Studies on the use of tranexamic acid (TXA) to improve clinical outcomes after joint arthroplasty have reported contrasting results between intravenous (IV) TXA alone and combined IV and intraarticular (IA) administration. We compared the effectiveness of the 2 methods in providing higher postoperative hemoglobin (Hb) levels in patients undergoing primary total knee arthroplasty (TKA).
Methods: A total of 100 TKA patients were randomly assigned to receive either IV TXA alone (group 1) or combined IV and topical IA TXA (group 2). Hb and hematocrit levels were measured before and after surgery. The amount of drained blood and transfused blood for the 2 groups was compared.
Results: The Hb level was significantly higher at postoperative day 4, together with a positive, albeit not significant, trend toward less postoperative blood loss in the group that received combined IV and IA TXA. No postoperative infections or deep venous thrombosis events occurred.
Conclusions: This study reinforces evidence that, as compared to IV TXA alone, combined IV and IA administration of TXA has a synergic effect, leading to higher postoperative Hb levels without influencing drug safety in TKA patients.
Arora M, Singh S, Gupta V, Dongre A, Shetty V
Eur J Orthop Surg Traumatol. 2018 Mar 29. doi: 10.1007/s00590-018-2194-y.
PURPOSE: To compare the effect of intravenous or intra-articular route of administration of tranexamic acid in reducing the blood loss in simultaneous bilateral total knee replacement surgeries performed without the use of tourniquets.
METHODS: Prospective cohort study of 30 consecutive patients grouped into two groups; Group 1: intravenous group and group 2: intra-articular group. Two outcome measures were studied; mean drop in post-operative haemoglobin and need for blood transfusion in both groups.
RESULTS: No significant difference in mean drop of haemoglobin and need for blood transfusion in both groups.
CONCLUSION: Route of administration of tranexamic acid does not influence on the mean drop of haemoglobin and need for blood transfusion in simultaneous bilateral total knee replacement surgeries performed without the use of tourniquet.
Boutonnet M, Abback P, Le Saché F, Harrois A, Follin A, Imbert N, Cap AP, Trichereau J, Ausset S; and the Traumabase Group.
J Trauma Acute Care Surg. 2018 Mar 12. Epub ahead of print
BACKGROUND: Tranexamic acid (TXA) use in severe trauma remains controversial notably because of concerns of the applicability of the CRASH-2 study findings in mature trauma systems. The aim of our study was to evaluate the outcomes of TXA administration in severely injured trauma patients managed in a mature trauma care system.
METHODS: We performed a retrospective study of data prospectively collected in the TraumaBase registry (a regional registry collecting the prehospital and hospital data of trauma patients admitted in 6 Level One Trauma Centers in Paris Area, France). In hospital mortality was compared between patients having received TXA or not in the early phase of resuscitation among those presenting an unstable hemodynamic state. Propensity score for TXA administration was calculated and results were adjusted for this score. Hemodynamic instability was defined by the need of packed red blood cells (pRBC) transfusion and/or vasopressor administration in the emergency room (ER).
RESULTS: Among patients meeting inclusion criteria (n=1476), the propensity score could be calculated in 797 and survival analysis could be achieved in 684/797. Four hundred and seventy (59%) received TXA and 327 (41%) did not. The overall hospital mortality rate was 25.7%. There was no effect of TXA use in the whole population but mortality was lowered by the use of TXA in patients requiring pRBC transfusion in the ER (HR= 0.3, CI 95= 0.3 - 0.6).
CONCLUSIONS: The use of TXA in the management of severely injured trauma patients, in a mature trauma care system, was not associated with reduction in the hospital mortality. An independent association with a better survival was found in a selected population of patients requiring pRBC transfusion in the ER.
LEVEL OF EVIDENCE: Level III STUDY TYPE: Therapeutic study.
El-Menyar A, Sathian B, Asim M, Latifi R, Al-Thani H
Am J Emerg Med. 2018 Mar 16. Epub ahead of print
OBJECTIVE: Antifibrinolytic agent tranexamic acid (TXA) has a potential clinical benefit for in-hospital patients with severe bleeding but its effectiveness in pre-hospital settings remains unclear. We conducted a systematic review and meta-analysis to evaluate whether pre-hospital administration of TXA compared to placebo improve patients' outcomes?
METHODS: PubMed, MEDLINE, Cochrane Library, WHO International Clinical Trials Registry Platform, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and Google scholar databases were searched for a retrospective, prospective and randomized (RCT) or quasi-RCT studies that assessed the effect of prehospital administration of TXA versus placebo on the outcomes of trauma patients with significant hemorrhage. The main outcomes of interest were 24hour 30-day mortality and in-hospital thromboembolic complications. Two authors independently abstracted the data using a data collection form. Results from different studies were pooled for the analysis, when appropriate.
RESULTS: Out of 92 references identified through the search, two analytical studies met the inclusion criteria. The effect of TXA on 24-hour mortality had a pooled odds ratio (OR) of 0.49 (95% CI 0.28-0.85), 30-day mortality OR of 0.86 (95% CI, 0.56-1.32), and thromboembolic events OR of 0.74 (95% CI, 0.27-2.07).
CONCLUSION: Prehospital TXA appears to reduce early mortality in trauma patients. The pooled analysis also shows a trend toward lower 30-day mortality and reduced risk of thromboembolic events. Additional randomized controlled clinical trials are needed to determine the significance of these trends.
Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, Bini SA, Clarke HD, Schemitsch E, Johnson RL, Memtsoudis SG, Sayeed SA, Sah AP, Della Valle CJ
J Arthroplasty. 2018 Mar 22. Epub ahead of print
BACKGROUND: Tranexamic acid (TXA) is effective in reducing blood loss in total joint arthroplasty (TJA), but concerns still remain regarding the drug's safety. The purpose of this direct meta-analysis was to evaluate and establish a basis for the safety recommendations of the combined clinical practice guidelines on the use of TXA in primary TJA.
METHODS: A search was completed for studies published before July 2017 on TXA in primary TJA. We performed qualitative and quantitative homogeneity testing and a direct comparison meta-analysis. We used the American Society of Anesthesiologists (ASA) score of 3 or greater as a proxy for patients at higher risk for complications in general and performed a meta-regression analysis to investigate the influence of comorbidity burden on the risk of arterial thromboembolic event and venous thromboembolic event (VTE).
RESULTS: Topical, intravenous, and oral TXA were not associated with an increased risk of VTE after TJA. In addition, meta-regression demonstrated that TXA use in patients with an ASA status of 3 or greater was not associated with an increased risk of VTE after total knee arthroplasty.
CONCLUSION: Although most studies included in our analysis excluded patients with a history of prior thromboembolic events, our findings support the lack of evidence of harm from TXA administration in patients undergoing TJA. Moderate evidence supports the safety of TXA in patients undergoing total knee arthroplasty with an ASA score of 3 or greater. The benefits of using TXA appear to outweigh the potential risks of thromboembolic events even in patients with a higher comorbidity.
Komura S, Rodriguez RM, Peabody CR
J Emerg Med. 2018 May;54(5):e97-e99
BACKGROUND: Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent used to prevent and treat various bleeding complications. In many studies, investigators have evaluated its utility and safety orally, intravenously, and topically, but few studies have described the potential benefits of nebulized TXA.
CASE REPORT: We present a case of massive hemoptysis treated with nebulized TXA in the emergency department (ED) that led to the cessation of bleeding and avoidance of endotracheal intubation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In massive hemoptysis, rapidly available nebulized TXA may be considered a therapeutic option, serving either as primary therapy or as a bridge until other definitive therapies can be arranged.
Meizoso JP, Dudaryk R, Mulder MB, Ray JJ, Karcutskie CA, Eidelson SA, Namias N, Schulman CI, Proctor KG.
J Trauma Acute Care Surg. 2018 Mar;84(3):426-432
BACKGROUND: The association between tranexamic acid (TXA) and fibrinolysis shutdown is unknown. We hypothesize that TXA is associated with fibrinolysis shutdown in critically injured trauma patients.
METHODS: Two hundred eighteen critically injured adults admitted to the intensive care unit at an urban Level I trauma center from August 2011 to January 2015 who had thromboelastography performed upon intensive care unit admission were reviewed. Groups were stratified based on fibrinolysis shutdown, which was defined as LY30 of 0.8% or less. Continuous variables were expressed as mean ± standard deviation or median (interquartile range). Poisson regression analysis was used to determine predictors of shutdown.
RESULTS: Patients were age 46 ± 18 years, 81% male, 75% blunt trauma, Injury Severity Score of 28 ± 13, 16% received TXA, 64% developed fibrinolysis shutdown, and mortality was 15%. In the first 24 hours, 4 (2-9) units packed red blood cells and 2 (0-6) units fresh frozen plasma were administered. Those with shutdown had worse initial systolic blood pressure (114 ± 38 mm Hg vs. 129 ± 43 mm Hg, p = 0.006) and base deficit (-5 ± 6 mEq/L vs -3 ± 5 mEq/L, p = 0.013); received more packed red blood cells [6 (2-11) vs. 2 (1-5) units, p < 0.0001], and fresh frozen plasma [3 (0-8) vs. 0 (0-4) units, p < 0.0001]; and more often received TXA (23% vs. 4%, p <0.0001). After controlling for confounders, TXA (relative risk, 1.35; 95% confidence interval, 1.10-1.64; p = 0.004) and cryoprecipitate transfusion (relative risk, 1.29; 95% confidence interval, 1.07-1.56; p = 0.007) were independently associated with fibrinolysis shutdown.
CONCLUSION: Patients who received TXA were at increased risk of fibrinolysis shutdown compared with patients who did not receive TXA. We recommend that administration of TXA be limited to severely injured patients with evidence of hyperfibrinolysis and recommend caution in those with evidence of fibrinolysis shutdown.
LEVEL OF EVIDENCE: Therapeutic, level III.
Naumann DN, Hazeldine J, Davies DJ, Bishop J, Midwinter MJ, Belli A, Harrison P, Lord JM
Shock. 2018 Apr;49(4):420-428
BACKGROUND: Trauma patients are vulnerable to coagulopathy and inflammatory dysfunction associated with endotheliopathy of trauma (EoT). In vitro evidence has suggested that tranexamic acid (TXA) may ameliorate endotheliopathy. We aimed to investigate how soon after injury EoT occurs, its association with multiple organ dysfunction syndrome (MODS), and whether TXA ameliorates it.
METHODS: A prospective observational study included 91 trauma patients enrolled within 60 min of injury and 19 healthy controls. Blood was sampled on enrolment and again 4 to 12 h later. ELISAs measured serum concentrations of syndecan-1 and thrombomodulin as biomarkers of EoT. MODS was compared between groups according to biomarker dynamics: persistently abnormal; abnormal to normal; and persistently normal. Timing of EoT was estimated by plotting biomarker data against time, and then fitting generalized additive models. Biomarker dynamics were compared between those who did or did not receive prehospital TXA.
RESULTS: Median age was 38 (interquartile range [IQR] 24-55) years; 78 of 91 were male. Median injury severity score (ISS) was 22 (IQR 12-36). EoT was estimated to occur at 5 to 8 min after injury. There were no significant differences in ISS between those with or without prehospital EoT. Forty-two patients developed MODS; 31 of 42 with persistently abnormal; 8 of 42 with abnormal to normal; and 3 of 42 with persistently normal biomarkers; P < 0.05. There were no significant differences between TXA and non-TXA groups.
CONCLUSIONS: EoT was present at the scene of injury. MODS was more likely when biomarkers of EoT were persistently raised. There were no significant differences between TXA and non-TXA groups. Prehospital interventions aimed at endothelial restoration may represent a clinically meaningful target for prehospital resuscitation.
Schauer SG, April MD, Naylor JF, Wiese J, Ryan KL, Fisher AD, Cunningham CW, Mitchell N, Antonacci MA.
J Spec Oper Med. Fall 2017;17(3):55-58.
BACKGROUND: Tranexamic acid (TXA) was shown to reduce overall mortality and death secondary to hemorrhage in a large prospective study. This intervention is time sensitive. As such, the Tactical Combat Casualty Care (TCCC) guidelines recommend use of this low-cost, safe intervention among patients with possible hemorrhagic shock, penetrating trauma to the thorax or trunk, or extremity amputation.
OBJECTIVE: Prehospital administration of TXA by ground forces in the Afghanistan combat theater is described.
METHODS: We obtained data from the Prehospital Trauma Registry. We searched for all patients with documented hypotension, amputation, or penetrating trauma to the torso.
RESULTS: From January 2013 to September 2014, there were 272 patients who met inclusion criteria. Most injuries (97.8%; n = 266) were battle injuries. Of the 272 patients who met criteria to receive prehospital TXA, 51 (18.8%) received TXA, whereas the remaining 221 (81.2%) did not. Higher proportions of patients receiving TXA versus patients not receiving TXA received hemostatic dressings, pressure dressings, and tourniquet placement. Conversely, the proportion of patients receiving intravenous fluids was higher in the no-TXA group.
CONCLUSION: Overall, proportions of eligible patients receiving TXA were low despite emphasis in the guidelines. The reasons for this low adherence to TCCC guidelines are likely multifactorial. Future research should seek to identify reasons TXA is not given when indicated and to develop training and technology to increase prehospital TXA administration.
Wang D, Zhu H, Meng WK, Wang HY, Luo ZY, Pei FX, Li Q, Zhou ZK
BMC Musculoskelet Disord. 2018 Mar 15;19(1):85
BACKGROUND: Although randomized controlled trials have confirmed oral tranexamic acid (TXA) can provide similar blood-sparing efficacy compared with intravenous (IV) TXA in total knee arthroplasty (TKA), some concerns do remain about thromboembolic events after such systemic administration. Many studies have confirmed that intra-articular (IA) application of TXA can show similar blood-saving efficacy with minimal levels of systemic absorption compared with IV TXA. However, it remains unclear whether the efficacy and safety of oral TXA administration is equal to or less than that of IA administration in TKA without the use of a tourniquet and drain. Thus, this study was to verify non-inferior efficacy and safety of oral TXA compared with IA TXA in primary TKA.
METHODS: A double-blind, randomized, controlled trial was performed to compare three oral doses of TXA (2 g of TXA 2 h before incision, and 1 g of TXA 6 and 12 h after surgery, respectively) with IA TXA (3 g of TXA in 100 mL of saline solution). One hundred forty-seven patients scheduled for TKA were randomized to one of the two interventions. The primary outcome was total blood loss. The secondary outcomes included reduction of hemoglobin concentration, clinical outcomes, blood coagulation values, thromboembolic complications, and transfusion rates.
RESULTS: The mean total blood loss was 788.8 mL in the oral TXA group compared with 872.4 mL in the IA TXA group, with no statistical significance (p > 0.05). There were no significant differences in reduction of hemoglobin level, blood coagulation level, and clinical outcomes. The transfusion rates were 4% in oral group and 5% IA group, respectively. Also, no significant differences were identified in thromboembolic complications.
CONCLUSION: Oral TXA according to the described protocol demonstrated non-inferiority for primary TKA, with no safety concerns and a greatly reduced cost, compared with the IA TXA. This randomized controlled trial supports the oral administration of TXA in TKA.
TRIAL REGISTRATION: The trial was registered in the Chinese Clinical TrialRegistry (ChiCTR-INR-17010968 ) dated 23rd March 2017.