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Editor's Choice
  • Yassi N
  • Zhao H
  • Churilov L
  • Wu TY
  • Ma H
  • et al.
Lancet Neurol. 2024 Jun;23(6):577-587 doi: 10.1016/S1474-4422(24)00128-5.
POPULATION:

Patients with intracerebral haemorrhage treated within 2 hours of symptom onset, enrolled in the STOP-MSU trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam (n= 201).

INTERVENTION:

Tranexamic acid (n= 103).

COMPARISON:

Placebo (n= 98).

OUTCOME:

Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio (aOR) 1.31; 95% CI [0.72, 2.40]). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0.02 95% CI [-0.02, 0.06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1.08 95% CI [0.35, 3.35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1.61; 95% CI [0.65, 3.98]).

BACKGROUND:

Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo.

METHODS:

STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete.

FINDINGS:

Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]).

INTERPRETATION:

Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings.

FUNDING:

Australian Government Medical Research Future Fund.

Editor's Choice
  • Brown AN
  • Yendluri A
  • Lawrence KW
  • Cordero JK
  • Moucha CS
  • et al.
J Am Acad Orthop Surg. 2024 Jun 1;32(11):508-515 doi: 10.5435/JAAOS-D-23-00503.
POPULATION:

Patients undergoing orthopaedic surgery (108 randomised controlled trials).

INTERVENTION:

Tranexamic acid (TXA).

COMPARISON:

Placebo/control; other antifibrinolytic/clotting agents; TXA with a different dose or route of administration.

OUTCOME:

A total of 192 outcomes were reported across the 108 included studies. The median fragility index (FI) of the 192 outcomes was 4 (IQR= 2, 5) with an associated fragility quotient (FQ) of 0.03 (IQR= 0.019, 0.050). 45 outcomes were reported as statistically significant with a median FI of 1 (IQR= 1, 5) and associated FQ of 0.02 (IQR= 0.011, 0.034). 147 outcomes were reported as nonsignificant with a median reverse fragility index of 4 (IQR= 3, 5) and associated FQ of 0.04 (IQR= 0.023, 0.051). The adult reconstruction, trauma, and spine subspecialties had a median FI of 4. Sports had a median FI of 3. Shoulder and elbow and foot and ankle had median FIs of 6.

INTRODUCTION:

Randomized controlled trials (RCTs) represent the highest level of evidence in orthopaedic surgery literature, although the robustness of statistical findings in these trials may be unreliable. We used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate the statistical stability of outcomes reported in RCTs that assess the use of tranexamic acid (TXA) across orthopaedic subspecialties.

METHODS:

PubMed, EMBASE, and MEDLINE were queried for RCTs (2010-present) reporting dichotomous outcomes with study groups stratified by TXA administration. The FI and rFI were defined as the number of outcome event reversals needed to alter the significance level of significant and nonsignificant outcomes, respectively. FQ was determined by dividing the FI or rFI by sample size. Subgroup analyses were conducted based on orthopaedic subspecialty.

RESULTS:

Six hundred five RCTs were screened with 108 studies included for analysis comprising 192 total outcomes. The median FI of the 192 outcomes was 4 (IQR 2 to 5) with an associated FQ of 0.03 (IQR 0.019 to 0.050). 45 outcomes were reported as statistically significant with a median FI of 1 (IQR 1 to 5) and associated FQ of 0.02 (IQR 0.011 to 0.034). 147 outcomes were reported as nonsignificant with a median rFI of 4 (IQR 3 to 5) and associated FQ of 0.04 (IQR 0.023 to 0.051). The adult reconstruction, trauma, and spine subspecialties had a median FI of 4. Sports had a median FI of 3. Shoulder and elbow and foot and ankle had median FIs of 6.

DISCUSSION:

Statistical outcomes reported in RCTs on the use of TXA in orthopaedic surgery are fragile. Reversal of a few outcomes is sufficient to alter statistical significance. We recommend reporting FI, rFI, and FQ metrics to aid in interpreting the outcomes reported in comparative trials.

Editor's Choice
  • Liu CW
  • Anih J
  • Lebedeva V
  • Gungor A
  • Wang C
  • et al.
J Clin Anesth. 2024 Jun;94:111417 doi: 10.1016/j.jclinane.2024.111417.
POPULATION:

Patients undergoing non-obstetric surgery (300 trials, n= 53,085).

INTERVENTION:

Intravenous tranexamic acid.

COMPARISON:

Placebo or usual care without tranexamic acid.

OUTCOME:

From all the included studies, 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with estimated glomerular filtration rate <60 mL/min/1.73m(2) (RR 0.95; 95% CI [0.83, 1.07]) or ≥ 60 mL/min/1.73m(2) (RR 1.00; 95% CI [0.91, 1.11], but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in non-cardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min.

STUDY OBJECTIVE:

To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function.

DESIGN:

Systematic review and meta-analysis of randomized controlled trials.

SETTING:

We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023.

PATIENTS:

Patients undergoing non-obstetric surgery.

INTERVENTIONS:

Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid.

MEASUREMENT:

We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function.

MAIN RESULTS:

We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min.

CONCLUSIONS:

The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.

Editor's Choice
  • Elmenawi KA
  • Mohamed FAE
  • Poilvache H
  • Prokop LJ
  • Abdel MP
  • et al.
J Arthroplasty. 2024 Apr 16; doi: 10.1016/j.arth.2024.04.033.
POPULATION:

Patients undergoing total hip and knee arthroplasty (6 studies n= >2million).

INTERVENTION:

Tranexamic acid (TXA).

COMPARISON:

No TXA.

OUTCOME:

Among 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of periprosthetic joint infection (PJI) (OR 0.63; 95% CI [0.42, 0.96]) and a 0.4% lower incidence of PJI (RD -0.0038; 95% CI [-0.005, -0.002]). When sub-grouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR 0.43; 95% CI [0.35, 0.53]) and a 1% lower incidence of PJI (RD -0.0095; 95% CI [-0.013, -0.005]) in patients followed for more than 90 days.

BACKGROUND:

The purpose of this study was to perform a systematic review and meta-analysis to evaluate the association between tranexamic acid (TXA) use during primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA), and the risk of developing periprosthetic joint infection (PJI) after these procedures.

METHODS:

A systematic review was carried out from inception to October 17, 2022. There were 6 studies that were ultimately included in the meta-analysis. The association between the development of PJI and TXA was analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and estimates of risk difference (RD). Subgroup analysis was performed to evaluate only studies reporting out to 90 days of follow-up versus more than 90 days of follow-up.

RESULTS:

Among 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of PJI (OR = 0.63 [95% CI 0.42 to 0.96], P < .001) and a 0.4% lower incidence of PJI (RD = -0.0038, 95% CI [-0.005 to -0.002], P < .001). When subgrouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR = 0.43 [95% CI 0.35 to 0.53], P < .001) and a 1% lower incidence of PJI (RD = -0.0095 [95% CI -0.013 to -0.005], P < .001) in patients followed for more than 90 days.

CONCLUSIONS:

This meta-analysis demonstrates that TXA use is associated with a reduced risk of PJI, with our RD analysis identifying an approximately 0.4% reduction in PJI rates with TXA use. These findings provide even more data to support the routine use of TXA during primary THA and primary TKA.

Editor's Choice
  • Provinciatto H
  • Barbalho ME
  • da Câmara PM
  • Donadon IB
  • Fonseca LM
  • et al.
Can J Anaesth. 2024 Apr;71(4):465-478 doi: 10.1007/s12630-024-02715-3.
POPULATION:

Patients undergoing caesarean delivery (38 randomised controlled trials, n= 22,940).

INTERVENTION:

Postpartum haemorrhage (PPH) prophylaxis with tranexamic acid (TXA).

COMPARISON:

Placebo or no treatment.

OUTCOME:

The main outcomes were PPH, blood transfusion, need for additional uterotonics, and adverse events. Patients treated with TXA had significantly fewer cases of PPH (risk ratio (RR) 0.51; 95% confidence interval (CI) [0.38, 0.69]); less blood transfusion (RR 0.43; 95% CI [0.30, 0.61]), and less use of additional uterotonics (RR 0.52; 95% CI [0.40, 0.68]). No significant differences were found between the groups in terms of adverse effects and thromboembolic events.

PURPOSE:

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Although several studies on the prophylactic use of tranexamic acid (TXA) in parturients undergoing Cesarean delivery have been published, conflicting results raise questions regarding its use. Thus, we aimed to investigate the safety and efficacy of PPH prophylaxis with TXA.

SOURCE:

We searched PubMed®, Embase, Cochrane Central, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing prophylactic TXA with placebo or no treatment in parturients undergoing Cesarean delivery. Our main outcomes were PPH, any blood transfusion, need for additional uterotonics, and adverse events. We performed a trial sequential analysis (TSA) of all outcomes to investigate the reliability and conclusiveness of findings.

PRINCIPAL FINDINGS:

We included 38 RCTs including 22,940 parturients, 11,535 (50%) of whom were randomized to receive prophylactic TXA. Patients treated with TXA had significantly fewer cases of PPH (risk ratio [RR], 0.51; 95% confidence interval [CI], 0.38 to 0.69; P < 0.001); less blood transfusion (RR, 0.43; 95% CI, 0.30 to 0.61; P < 0.001), and less use of additional uterotonics (RR, 0.52; 95% CI, 0.40 to 0.68; P < 0.001). No significant differences were found between the groups in terms of adverse effects and thromboembolic events.

CONCLUSION:

Prophylactic TXA administration for parturients undergoing Cesarean delivery significantly reduced blood loss, without increasing adverse events, supporting its use as a safe and effective strategy for reducing PPH in this population.

STUDY REGISTRATION:

PROSPERO (CRD42023422188); first submitted 27 April 2023.

Editor's Choice
  • Mazzei M
  • Donohue JK
  • Schreiber M
  • Rowell S
  • Guyette FX
  • et al.
J Trauma Acute Care Surg. 2024 Mar 25; doi: 10.1097/TA.0000000000004315.
POPULATION:

Patients with major traumatic injury from the STAAMP and the ROC-TXA harmonised clinical trials (n= 1,744).

INTERVENTION:

Prehospital tranexamic acid (TXA) (n= 1,016).

COMPARISON:

Placebo (n= 728).

OUTCOME:

The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR= 5, 26). TXA was independently associated with a lower risk of 28-day mortality (HR 0.72; 95% CI [0.54, 0.96]). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR 0.78; 95% CI [0.63, 0.96]). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (β -0.31; 95% CI [-0.61, -0.01]) with a dose-response relationship (β -0.24; 95% CI [-0.45, -0.02]). There was no independent association of prehospital TXA administration on venous thromboembolism, seizure, or stroke.

INTRODUCTION:

Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation.

METHODS:

A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered.

RESULTS:

A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (β: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (β: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke.

CONCLUSIONS:

In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship.

LEVEL OF EVIDENCE:

Therapeutic/Care Management; Level III.

Editor's Choice
  • Zhang M
  • Liu T
Am J Emerg Med. 2024 Mar 13;80:35-43 doi: 10.1016/j.ajem.2024.03.005.
POPULATION:

Adults with traumatic brain injury (11 randomised controlled trials, n= 11,299).

INTERVENTION:

Tranexamic acid (TXA) (n= 5,876).

COMPARISON:

Placebo (n= 5,423).

OUTCOME:

The primary outcome was mortality, poor clinical outcomes, haemorrhagic expansion and mean haemorrhage volume. TXA had no effect on mortality (risk ratio (RR) 0.93 [95% confidence interval 0.86, 1.00]), poor clinical outcomes (RR 0.92 [0.78, 1.09]), adverse events (RR 0.94 [0.83, 1.07]), vascular occlusive events (RR 0.85 [0.68, 1.06]), pulmonary embolism (RR 0.76 [0.47, 1.22]), seizure (RR 1.11 [0.92, 1.35]) and haemorrhagic complications (RR 0.78 [0.55, 1.09]). TXA might reduce the rate of haemorrhagic expansion (RR 0.83 [0.70, 0.99]) and mean haemorrhage volume (standardized mean difference (SMD) -0.39 [-0.60, -0.18]). When the time interval from symptom onset to treatment was <3 h, TXA reduced mean haemorrhage volume (SMD -0.51 [-0.81, -0.20]).

INTRODUCTION:

Tranexamic acid (TXA) holds a pivotal role in the therapeutic approach to traumatic conditions. Nevertheless, its precise influence on diminishing mortality and limiting the progression of intracranial hemorrhage (ICH) during the treatment of traumatic brain injury (TBI) remains indeterminate.

METHODS:

PubMed, EMBASE, Cochrane Library, and Web of Science were searched for randomized controlled trials that compared TXA and a placebo in adults with TBI up to September 31, 2023. Two authors independently abstracted the data and assessed the quality of evidence. Additionally, subgroup analyses were performed to assess outcomes with low heterogenety.

RESULTS:

Our search strategy yielded 11,299 patients from 11 studies. The result showed that TXA had no effect on mortality (RR 0.93 [0.86, 1.00], p = 0.06; I2: 0%, p = 0.79), poor clinical outcomes (RR 0.92 [0.78, 1.09], p = 0.34; I2: 0%, p = 0.40), adverse events (RR 0.94 [0.83, 1.07], p = 0.34; I2: 48%, p = 0.10), vascular occlusive events (RR 0.85 [0.68, 1.06], p = 0.16; I2: 32%, p = 0.22), pulmonary embolism (RR 0.76 [0.47, 1.22], p = 0.26; I2: 0%, p = 0.83), seizure (RR 1.11 [0.92, 1.35], p = 0.27; I2: 0%, p = 0.49) and hemorrhagic complications (RR 0.78 [0.55, 1.09], p = 0.14; I2: 0%, p = 0.42). TXA might reduce the rate of hemorrhagic expansion (RR 0.83 [0.70, 0.99], p = 0.03; I2: 18%, p = 0.29) and mean hemorrhage volume (SMD -0.39 [-0.60, -0.18], p <0.001; I2: 44%, p = 0.13).When the time interval from symptom onset to treatment was <3 h, TXA reduced mean hemorrhage volume (SMD -0.51 [-0.81, -0.20], p = 0.001; I2: 0%, p = 0.94).

CONCLUSIONS:

TXA did not elevate the risk of adverse event, however, the lack of reduction in mortality and the poor clinical outcomes constrain the value of clinical application. Early administration of TXA (within 3 h) may significantly decrease the likelihood of ICH growth in patients with TBI.

Editor's Choice
  • Poston JN
  • Brown SP
  • Ilich A
  • Ginsburg AS
  • Herren H
  • et al.
Res Pract Thromb Haemost. 2024 Mar 1;8(2):102358 doi: 10.1016/j.rpth.2024.102358.
POPULATION:

Adult patients with a haematologic malignancy or aplasia undergoing chemotherapy, immunotherapy, or haematopoietic stem cell transplant, enrolled in the A-TREAT trial (n= 326).

INTERVENTION:

Tranexamic acid (TXA) (n= 163).

COMPARISON:

Placebo (n= 163).

OUTCOME:

This study was a post hoc analysis of the A-TREAT clinical trial data. TXA did not change the overall rate of infections, but the rate of severe infections (Common Toxicology Criteria for Adverse Events grade 3+) was lower in patients who received TXA compared with the placebo group. Patients who experienced grade 3+ infections had higher rates of World Health Organization grade 2+ bleeding and red blood cell transfusion requirements than patients who did not experience a grade 3+ infection, irrespective of treatment group. TXA did not impact other inflammatory outcomes such as mucositis, rash, or graft vs. host disease.

BACKGROUND:

Tranexamic acid (TXA) is an antifibrinolytic agent that reduces bleeding in a multitude of clinical settings from postpartum hemorrhage to trauma. TXA may have clinical effects unrelated to bleeding; plasminogen, the target of TXA, alters immune responses, and TXA appears to decrease the risk of infection in patients undergoing cardiac surgery, as well as joint arthroplasty.

OBJECTIVES:

To address whether TXA alters rates of infection and inflammatory outcomes in patients with hematologic malignancies.

METHODS:

We performed a post hoc analysis of outcomes of patients randomized to receive either TXA or placebo in the double-blinded, multicenter American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (Clinicaltrials.gov identifier: NCT02578901).

RESULTS:

TXA did not change the overall rate of infections, but the rate of severe infections (Common Toxicology Criteria for Adverse Events grade 3+) was lower in patients who received TXA compared with the placebo group. Patients who experienced grade 3+ infections had higher rates of World Health Organization grade 2+ bleeding and red blood cell transfusion requirements than patients who did not experience a grade 3+ infection, irrespective of treatment group. TXA did not impact other inflammatory outcomes such as mucositis, rash, or graft vs host disease.

CONCLUSION:

Patients with hematologic malignancies who received TXA had less severe infections than those who received placebo with no difference in overall rate of infection or other inflammatory outcomes. Further investigation is needed on the impact of TXA on infections in this population.

Editor's Choice
  • Donohue JK
  • Iyanna N
  • Lorence JM
  • Brown JB
  • Guyette FX
  • et al.
Trauma Surg Acute Care Open. 2024 Feb 17;9(1):e001346 doi: 10.1136/tsaco-2023-001346.
POPULATION:

Patients at risk for haemorrhage receiving tranexamic acid before hospitalization, enrolled in the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP) Trial (n= 903).

INTERVENTION:

Prehospital tranexamic acid (TXA) (n= 447).

COMPARISON:

Placebo (n= 456).

OUTCOME:

This study was a secondary analysis of the STAAMP trial, comparing patients that received thromboelastography (TEG) (YES-TEG, n= 837) and patients unable to be sampled (NO-TEG, n= 66) to analyze subgroups in which to investigate TEG differences. NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs. 125 (88, 147)), lower prehospital Glascow Coma Score (14 (3, 15) vs. 15 (12, 15)), greater rates of prehospital intubation (39.4% vs. 24.4%) and greater mortality at 30 days (36.4% vs. 6.8%). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs. 1.1 (1.0, 1.2)). Within a severe prehospital shock cohort (SBP< 70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β= -27.6; 95% CI [-51.3, -3.9].

BACKGROUND:

Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings.

METHODS:

We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis.

RESULTS:

NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β=-27.6, 95% CI (-51.3 to -3.9), p=0.02).

CONCLUSIONS:

Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity.

LEVEL OF EVIDENCE:

Level II.