Tranexamic Acid for Acute Bleeding in Severely Traumatized Patients

Summary

Background:

The optimal use of tranexamic acid (TXA) in trauma care is a matter of intense discussion, particularly with respect to its indications, dosage, temporal window, and thromboembolic adverse effects.

Methods:

This review is based on publications retrieved by a selective literature search on the indications, effects, mechanism of action, and side effects of TXA (January 2022 to December 2025). Three randomized, controlled trials (RCTs), three observational studies, eight secondary analyses, and 16 meta-analyses were evaluated.

Results:

TXA administration lowers the mortality of severely traumatized patients (e.g., with a relative risk [RR] of 0.73 [0.56;0.96]). The currently available evidence is inconsistent, and many of the effects found in published studies lie within the range of random fluctuation. The reduction of mortality depends on TXA administration at the earliest possible time in the first 90 minutes after trauma (this temporal window is more important than the question of pre- vs. in-hospital administration), as well as on the nature of the injury, particularly in patients with hemorrhagic shock. Among patients with isolated traumatic brain injury, no consistent effect on mortality has been shown, but there may be an effect on the progression of intracranial bleeding. Multiple studies point to a thromboembolic risk, which is dosedependent, with a marked rise at 4 g (hazard ratio [HR] 5.33, 95% confidence interval [1.94;14.63]). In patients without shock, the reported absolute risk difference for mortality ranges from −5% to +5%, and that for thromboembolic adverse events from −0.2% to +4%.

Conclusion:

For trauma patients with lifethreatening hemorrhage, especially those in hemorrhagic shock, it is recommended that TXA be given as early as possible (before arrival in the hospital) in a single dose of 1–2 g (15–30 mg/kg body weight [BW]). When this is done, the benefit appears to be greater than the thromboembolic risk.

Information on CME.

This article has been certified by the North Rhine Academy for Continuing Medical Education. The questions on this article may be found (in German) at https://daebl.de/RY95 (Deutsches Ärzteblatt’s CME portal). Their English translation may be found in the PDF version of this article. The closing date for entries is June 11, 2027. Participation is possible at cme.aerzteblatt.de

The Trauma Register of the German Society for Trauma Surgery (TraumaRegister DGU®) includes 28 184 patients nationwide for the year 2024. Of these, 22.2% had a pre-existing clotting disorder, 20.6% were receiving hemostatic drug therapy, while only 14.3% received tranexamic acid (TXA). Furthermore, only 45% of those trauma patients who were transfused were given TXA before hospital admission (e1). Following publication of the randomized controlled trial (RCT) CRASH-2, acute care of patients with traumatic injury is now unimaginable without the use of TXA (e2). In that RCT, 20 211 trauma patients had received either placebo or a 1 g loading dose of TXA followed by another 1 g over eight hours within eight hours of injury. All-cause mortality was reduced by an absolute 1.5% (TXA 14.5% versus placebo 16.0%; relative risk [RR] 0.91; 95% confidence interval: [0.85; 0.97]). The risk of death due to bleeding was also reduced by 0.8% (4.9% versus 5.7%; RR 0.85 [0.76; 0.96]). The CRASH-3 trial demonstrated an absolute reduction of head injury-related death in patients with traumatic brain injury (TBI) by 1.3% (18.5% versus 19.8%; RR 0.94 [0.86; 1.02]) (e3). Despite these major trials and subsequent smaller investigations, the optimal use of TXA remains a matter of intense discussion—especially with respect to indications, dosage, temporal window, and thromboembolic risk (TE). The present article summarizes the available evidence on the use of TXA for acute bleeding in severely injured patients, taking into account the literature published since the last update of the AWMF (Association of Scientific Medical Societies in Germany) clinical practice guideline “Polytrauma/Treatment of the Severely Injured Patient” (e4).

Methods

The present review article is based on publications retrieved by a selective literature search using search strategies with various combinations of relevant search terms (“trauma/traumatic”, “bleeding/ hemorrhage”, “coagulopathy”, “management”, “tranexamic acid/ TXA”, “outcome”, “mortality”, “transfusion”) in the databases MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and Epistemonikos covering the period from January 2022 to December 2025. The literature search was specifically limited to the period since completion of the literature search for the previous AWMF clinical practice guideline, “Polytrauma/Treatment of the Severely Injured Patient” (e4). After removal of duplicates, 79 articles were reviewed in full text. The analysis of thromboembolic events focused on the following aspects:

• indication

• mechanism of action

• use

• benefits and risks.

Thirty publications with different study designs were included: three RCTs (1–3), three observational studies (4–6), eight secondary analyses (7–14), and 16 meta-analyses (15–30) (eTable). Relevant older evidence was also taken into account for specific questions.

eTable. Complete list of the included studies on survival, neurological outcome, and thromboembolic risk^*1.

Reference	Design	Main patient characteristics	Outcome*2		Complication*3
			absolute	relative	absolute	relative
Knudson et al. 2022 (4)	Prospective cohorts n = 7880 Risk factors for posttraumatic TE	18- to 40-year-old trauma patients			DVT
						OR 2.49 [1.80; 3.43]
					PE
						OR 3.96 [1.92; 8.13]
van Wessem et al. 2022 (5)	Prospective cohorts n = 234 Prehospital TXA vs. placebo	Trauma with severe TBI (SBP ≤90 mm Hg); 98% blunt trauma	Mortality (overall)
			27% vs. 22%; RD + 5%; p = 0.45
			Mortality (SBP on arrival ≤90 mm Hg)
			43% vs. 20%; RD + 23%; p = 0.18
El-Menyar et al. 2022 (1)	RCT n = 220 TXA pre- and in-hospital vs. prehospital only	85% blunt trauma	24-hour mortality		TE
			0.9% vs. 0.9%	RR 1.00 [0.24; 4.02]	2.7% vs. 1.8%; RD + 0.9%	RR 1.206 [0.58; 2.49]
			28-day mortality
			9.1% vs. 4.5%; RD + 4.6%	RR 1.36 [0.93; 2.00]
Ageron et al. 2022 (7)	Secondary analysis of CRASH-2 and CRASH-3 n = 32 944 TXA vs. placebo	Trauma with/without TBI	Mortality (all-cause; TXA <3 hrs)		TE (overall)
			5.7% vs. 7.2%; RD − 1.5%	OR 1.28 [1.15; 1.42]	1.6% vs. 1.8%; RD − 0.2%	OR 0.88 [0.74; 1.04]
			Mortality (severely injured; TXA <3 hrs)		TE (severely injured)
			14.5% vs. 17.5%; RD − 3%	OR 1.25 [1.10; 1.42]	2.9% vs. 3.0%; RD − 0.1%	OR 0.97 [0.77; 1.23]
			Mortality (severely injured; TXA <1 hr)
				OR 1.27 [1.03; 1.56]
			Mortality (severely injured; TXA 1-3 hrs)
				OR 1.24 [1.05; 1.46]
			Mortality (severely injured; TXA > 3 hrs)
				OR 1.14 [0.90; 1.45]
Spinella et al. 2022 (8)	Secondary analysis of TAMPITI n = 149 TXA 4 g vs. 2 g vs. placebo	~ 80% penetrating injury			TE
					32% vs. 26.5% vs. 12%	2 g: HR 3.20 [1.12; 9.11] 4 g: HR 5.33 [1.94; 14.63]
Huang et al. 2022 (15)	Meta-analysis 13 RCTs n = 18 675 TXA vs. placebo	SHT	Mortality (overall)		TE
			19.8% vs. 20.8%; RD − 1%	RR 0.99 [0.92; 1.06]	2.3% vs. 1.9%; RD + 0.4%	RR 1.05 [0.83; 1.33]
			GOS score <4 (unfavorable outcome)
			58.7% vs. 57.8%; RD + 0.9%	RR 0.96 [0.82; 1.11]
Germans et al. 2023 (16)	Meta-analysis 11 RCTs n = 2717 TXA vs. placebo	Aneurysmal SAH	Poor neurological outcome
			41.5% vs. 40.5%; RD + 1.0%	RR 1.03 [0.94; 1.13]
Xiong et al. 2023 (17)	Meta-analysis 25 RCTs n = 20 146 TXA vs. placebo	ICH	Mortality (ICH)
			20.7% vs. 20.4%; RD + 0.3%	OR 1.02 [0.84; 1.23]
			ICH: mRS ≤2 (favorable outcome)
			30.7% vs. 29.6%; RD + 1.1%	OR 1.05 [0.89; 1.24]
			Mortality (SAH)		DVT (SAH)
			27.8% vs. 28.3%; RD − 0.5%	OR 0.84 [0.54; 1.31]	1.8% vs. 1.7%: RD + 0.1%	OR 1.08 [0.51; 2.30]
			Mortality (TBI)		PE (TBI)
			16.5% vs. 16.7%; RD + 0.2%	OR 0.91 [0.69; 1.21]	0.6% vs. 0.6%	OR 1.22 [0.45; 3.27]
Deeb et al. 2023 (9)	Secondary analysis of PAMPer and STAAMP n = 1504 Risk of death per minute delay and prehospital vs. in-hospital	86% blunt trauma	24-hour mortality
			+ 1.5% per minute delay	aOR 1.01 [1.00; 1.02]
			24-hour mortality (prehospital)
				aOR 0.42 [0.21; 0.83]
			24-hour mortality (in-hospital)
				aOR 0.58 [0.19; 1.75]
			30-day mortality
			+ 2% per minute delay	aOR 1.02 [1.00; 1.03]
Biffi et al. 2023 (18)	Meta-analysis 5 RCTs n = 34 882 TXA prehospital vs. placebo	Trauma with/ without TBI	24-hour mortality (overall)
				RR 0.83 [0.74; 0.95]
			28-day mortality (overall)
				RR 0.93 [0.88; 0.97]
			28-day mortality (with TBI)
				RR 0.96 [0.89; 1.03]
			28-day mortality (with TBI and severe hemorrhage)
				RR 0.72 [0.49; 1.05]
PATCH-Trauma Investigators et al. 2023 (2)	RCT n = 1310 TXA prehospital vs. placebo	>90% blunt trauma	GOS-E score ≥5 (favorable outcome) and AIS head <2		TE
			70.2% vs. 66.1%; RD + 4.1%	RR 1.06 [0.96; 1.18]	23.6% vs. 19.7%; RD + 3.9%	RR 1.20 [0.97; 1.48]
			GOS-E score ≥5 (favorable outcome) and AIS head >2
			35.4% vs. 38.2% RD − 2.8%	RR 0.93 [0.73; 1.18]
			24-hour mortality
			9.7% vs. 14.1%; RD − 4.4%	RR 0.69 [0.51; 0.94]
			28-day mortality
			17.3% vs. 21.8%; RD − 4.5%	RR 0.79 [0.63; 0.99]
			6-month mortality
			19.0% vs. 22.9%; RD − 3.9%	RR 0.83 [0.67; 1.03]
Acharya et al. 2023 (19)	Meta-analysis 3 RCTs n = 3081 TXA prehospital vs. placebo	> 80% blunt trauma	GOS-E score ≥5 (favorable outcome)		TE
			56.8% vs. 55.6%; RD + 1.2%	RR 1.00 [0.93; 1.09]	12.8% vs. 12.6%; RD + 0.2%	RR 1.04 [0.72; 1.49]
			24-hour mortality
			7.2% vs. 9.7%; RD − 2.5%	RR 0.73 [0.56; 0.96]
			28-day mortality
			14.2% vs. 16.9%; RD − 2.7%	RR 0.82 [0.69; 0.97]
Gunn et al. 2024 (10)	Subgroup of the prospective A CIT-2 trial n = 525 TXA 1 g bolus vs. 1 g + 1 g infusion vs. 2 g or. 2× 1 g	59% blunt trauma	24-hour mortality		VTE
			10% vs. 6% vs. 11%; p = 0.51	OR 1.72 [0.41; 7.13] vs. 1 vs. 1.17 [0.25; 5.41]	4% vs. 8% vs. 7%; p = 0.31	OR 0.75 [0.26; 2.18] vs. 1 vs. 1.07 [0.33; 3.47]
			28-day mortality
			21% vs. 21% vs. 21%
Song et al. 2024 (20)	Meta-analysis 10 RCTs n = 10 954 TXA vs. placebo	TBI	Mortality		PE
			17.5% vs. 19.1%; RD − 1.6%	RR 0.92 [0.85; 1.0]	0.7% vs. 0.5%; RD + 0.2%	RR 1.33 [0.56; 3.15]
Mazzei et al. 2024 (11)	Secondary analysis of 2 RCTs n = 1744 TXA prehospital vs. placebo	~90% blunt trauma	28-day mortality		VTE
			10.5% vs. 12.1%; RD − 1.6%	HR 0.72 [0.54; 0.96]	3.8% vs. 3.6%; RD + 0.2%	OR 1.10 [0.66; 1.86]
Fouche et al. 2024 (21)	Meta-analysis 7 RCTs n = 32 832 TXA vs. placebo	Trauma with/ without TBI *corrected according to information provided by Francsois Fouche	28-day mortality (overall)		TE
			RD − 1.7% [- 2.4; - 0.7]*; NNT 61 [42; 135]	OR 0.89 [0.84; 0.95]		OR 0.96 [0.73; 1.27]
			24-hour mortality (overall)
				OR 0.76 [0.65; 0.88]
			28-day mortality (TBI)
			RD − 1.3% [−2.80; 0.3]*; NNT 78 [36; 317]	OR 0.92 [0.84; 1.02]
			28-day mortality (trauma)
			RD − 1.7% [−2.5; −0.7]*; NNT 61 [40; 147]	OR 0.88 [0.82; 0.94]
			28-day mortality (TXA in-hospital)
			RD − 1.4% [−2.4; −0.6]*; NNT 70 [42; 159]	OR 0.91 [0.85; 0.96]
			28-day mortality (TXA prehospital)
			RD − 3.1% [−5.1; −0.7]*; NNT 33 [20; 148]	OR 0.78 [0.64; 0.95]
Yassi et al. 2024 (3)	RCT n = 201 TXA vs. placebo	ICH	90-day mortality		TE
			18% vs. 15%; RD + 3% [- 4; + 13]	aOR 1.61 [0.65; 3.98]	3% vs. 1%; RD + 2% [- 2%; 6%]
			7-day mortality
			8% vs. 8%; RD 0% [- 6; 7]	aOR 1.08 [0.35; 3.35]
			mRS <3 (favorable outcome)
			30% vs. 32%; RD − 2%	aOR 0.77 [0.38; 1.56]
Zhang et al. 2024 (22)	Meta-analysis 11 RCTs n = 11 299 TXA vs. placebo	TBI	Mortality (overall)		TE
			17.6% vs. 19.0%; RD − 1.4%	RR 0.93 [0.86; 1.00]	2.0% vs. 2.1%; RD − 0.1%	RR 0.85 [0.68;1.06]
			GOS score ≤4 (unfavorable outcome)
			32.1% vs. 30.6%; RD + 1.5%	RR 0.92 [0.78; 1.09]
Tran et al. 2024 (23)	Meta-analysis 30 RCTs and cohorts n = 1 981 946 Risk factors for posttraumatic VTE	Various types of injury			VTE
						OR 2.84 [1.58;5.11]
Chen et al. 2024 (24)	Meta-analysis 2 RCTs + 9 cohorts n = 11 259 TXA prehospital vs. control	Predominantly blunt trauma	24-hour mortality		TE
			10.06% vs. 11.97%; RD − 1.91%	OR 0.82 [0.71;0.94]	8.1% vs. 6.7%; RD + 1.4%	OR 1.22 [1.03;1.44]
Rowell et al. 2024 (12)	Subgroup of the RCT “prehospital TXA for TBI” n = 966 TXA prehospital 1 g + 1 g infusion vs. prehospital 2 g vs. placebo	TBI	28-day mortality		TE
			26% vs. 17% vs. 27%	adjusted difference with ICH: 1 g + 1 g vs. placebo: 0.7 [- 7.2; 8.5] 2 g vs. placebo: −8.5 [−15.9; −1.0] 2 g vs. 1 g + 1 g: −10.2 [−17.6; −2.9]	6% vs. 13% vs. 14%
			24-hour mortality
			6% vs. 4% vs. 12%
			GOS-E score <4 (unfavorable outcome)
			with ICH: 53% vs. 45% vs. 50% without ICH: 11% vs. 20% vs. 19%	adjusted difference with ICH: 1 g + 1 g vs. placebo: 3.8 [−5.3; 13.0] 2 g vs. placebo: −4.6 [−13.7; 4.6] 2 g vs. 1 g + 1 g: −8.4 [−17.5; 0.7]
Li et al. 2025 (25)	Meta-analysis 5 multi-center RCTs + 5 multi-center cohorts + 2 single-center cohorts n = 12 682 prehospital TXA vs. no TXA	Trauma patients	24-hour mortality		VTE
			9.6% vs. 11.9%; RD − 2.3%	OR 072 [0.54; 0.94]	8.0% vs. 6.9%; RD + 1.1%	OR 1.14 [0.98; 1.33]
			28-day mortality
			19.8% vs. 21.0%; RD − 1.2%	OR 0.92 [0.74; 1.14]
			mortality (overall)
			21.7% vs. 23.4%; RD − 1.7%	OR 0.91 [0.82; 1.01]
Osawa et al. 2025 (13)	Secondary analysis CRASH-2 and CRASH-3 n = 28 448; TXA vs. no TXA	Trauma with/ without TBI	24-hour mortality (GCS score <9 or TXA <2 hours
			4.2% vs. 5.8%; RD − 1.5% [−0.87; −2.2]	RR 0.73 [0.64; 0.84]
			24-hour mortality (all others)
			1.6% vs. 1.3%; RD + 0.34% [+ 0.80; −0.11]	RR 1.27 [0.94; 1.72]
Lee et al. 2025 (26)	Meta-analysis 25 RCTs n = 16 677 TXA vs. no TXA	TBI	Mortality (overall)		TE
				RR 0.96 [0.91; 1.03]		RR 1.11 [0.97; 1.28]
					TE (TXA > 8 hrs)
					RR 1.16 [1.02; 1.33]
			30-day mortality		TE (TXA > 1 day)
				RR 0.92 [O.84; 1.O1]		RR 1.22 [1.03; 1.44]
Utsumi et al. 2025 (27)	Meta-analysis 10 RCTs n = 11 237 TXA vs. no TXA	TBI	Mortality (TXA <3 hours)		TE
			Placebo vs. 1 g bolus + 1 g/8 hours:
				RR 1.1O [1.OO; 1.21]		RR 1.26 [0.69; 2.30]
			Placebo vs. 2 g bolus:
				RR 1.66 [1.11; 2.46]		RR 0.87 [0.30; 2.52]
			1 g bolus + 1 g/8 hours vs. 2 g bolus:
				RR 1.51 [1.O1; 2.24]		RR 0.69 [0.23; 2.04]
Steiner et al. 2025 (28)	Meta-analysis 8 RCTs n = 3061 TXA vs. placebo	Stroke due to spontaneous ICH	90-day mortality		TE
			19.1% vs. 19.1%	OR 1.00 [0.83; 1.20]	4.7% vs. 4.0%; RD + 0.7%	OR 1.18 [0.82; 1.68]
			7-day mortality
			8.6% vs. 10.3%; RD − 1.7	OR 0.82 [0.63; 1.07]
Bayer et al. 2025 (6)	TR-DGU cohort study n = 37 342 TXA vs. placebo	>95% blunt trauma			VTE
					5.5% vs. 2.3%; RD + 3.2%	1× TXA: aOR 1.56 [1.35; 1.81] p <0 .001; 2× TXA: aOR 1.79 [1.43; 2.24] p < 0.001; 3× TXA: aOR 1.50 [0.91; 2.48]
Lin et al. 2025 (29)	Meta-analysis 1 RCTs + 9 cohorts n = 6759 TXA vs. placebo	Pediatric trauma cases	Mortality		TE
				aOR 0.58 [O.38; O.89]		OR 1.01 [0.32; 3.24]
Bian et al. 2025 (30)	Meta-analysis 10 RCTs + 6 cohorts n= 15015 TXA vs. placebo	Isolated TBI	28-day mortality (GCS score ≥9)
				RR 0.71 [0.60; 0.85]
			28-day mortality (GCS score ≥9)
				RR 1.05 [0.93; 1.19]
Ali et al. 2026 (14)	Secondary analysis of PATCH-Trauma trial n = 1287 TXA vs. placebo		28-day mortality		TE
			17% vs. 22%; RD − 5%	aRR 0.78 [O.64; O.95]	24% vs. 20%; RD + 4%	aRR 1.21 [O.98; 1.49]

^*1Always TXA versus control. The primary outcome is printed in bold.

^*2RR or OR [95% CI]

^*3Incidence and RR or OR [95% CI]

AIS, Abbreviated Injury Scale; aOR, adjusted odds ratio; aRR, adjusted relative risk; GCS, Glasgow Coma Scale;

GOS, Glasgow Outcome Scale (higher scores reflect better overall recovery; a score of 4 indicates a favorable outcome, defined as moderate neurological disability);

GOS-E, Glasgow Outcome Scale – Extended (higher scores reflect better overall recovery; a score of 4 indicates a favorable outcome, defined as moderate neurological disability); HR, hazard ratio; ICH, intracranial hemorrhage; CI, confidence interval; PE, pulmonary embolism;

mRS, modified Rankin Scale (higher scores reflect worse outcomes; a score of 3 indicates that the patient requires assistance with daily activities); n; sample size;

NNT, number needed to treat; OR, odds ratio; pats., patients; RCT, randomized controlled trial; RD, risk difference; RR, relative risk; SAH, subarachnoid hemorrhage;

SBP, systolic blood pressure; TBI, traumatic brain injury; TE, thromboembolism; TR-DGU TraumaRegister of the German Society for Trauma Surgery;

DVT, deep vein thrombosis; TXA, tranexamic acid; vs., versus; VTE venous thromboembolism

Trauma-induced coagulopathy

Cellular hypoxia and hypoperfusion secondary to massive tissue destruction result in the release of tissue plasminogen activator (tPA) from the endothelium. This enzyme activates plasminogen, which, after conversion to plasmin, promotes accelerated fibrin breakdown. Furthermore, the physiological inhibition of tPA by plasminogen activator inhibitor-1 (PAI-1) no longer occurs. The result of endothelial activation is the phenomenon known as the endotheliopathy of trauma, which can cause marked hyperfibrinolysis and is exacerbated by the “lethal triad” of hypothermia, acidosis, and coagulopathy. A distinction is made between different fibrinolytic phenotypes using specific viscoelastic test profiles (Box 1). Whereas in hyperfibrinolysis the blood clot is dissolved too rapidly and to an excessive degree, the opposite is the case with hypofibrinolysis and fibrinolysis shutdown. Patients with hyperfibrinolysis are more severely injured than those with the other two phenotypes and often suffer from impaired perfusion, with markedly increased mortality (e5–e8).

Box 1. Physiological responses to severe traumatic injury* ^*1.

• Hyperfibrinolysis^*2

  • –
    rapid, sustained, and excessive activation
  • –
    incidence ~ 20%
  • –
    mortality >40%
• Physiological fibrinolysis

  • –
    brief activation of fibrinolysis followed by rapid suppression
  • –
    incidence <20%
  • –
    mortality <5%
• Low fibrinolytic activity

  • –
    fibrinolytic shutdown^*2

    • –
      low fibrinolytic activity after initial activation
    • –
      tPA-responsive
  • –
    hypofibrinolysis^*2

    • –
      low fibrinolytic activity without initial activation
    • –
      tPA-resistant
  • incidence of fibrinolytic shutdown and hypofibrinolysis >60%
  • mortality for fibrinolytic shutdown and hypofibrinolysis ~ 20%

Mechanism of action of tranexamic acid

TXA is a synthetic lysine analog that competitively blocks the lysine-binding sites of plasminogen, thereby inhibiting the fibrin-dependent activation of tPA. Further examples of antifibrinolytics are aprotinin and epsilon aminocaproic acid. Box 2 provides a brief pharmacokinetic overview of TXA (e9, e10). There are no studies available that have specifically defined the pharmacokinetic profile of TXA or the plasma concentrations required for therapeutic efficacy in patients with multiple injuries (e11). Despite the reported elimination half-life of two to three hours, plasma concentrations were still detected after 42 to 96 hours and remained sufficient to inhibit fibrinolysis (e12, e13).

Box 2. Brief pharmacokinetic overview of TXA^*.

• elimination half-life of 2–3 hours; TXA remains in serum for 8 hours and in tissue for 17 hours, 90% is excreted with the urine within one day (corresponding to the GFR)

• similar onset of action is observed following IV (3–5 minutes), IM (5–7 minutes), and IO (7–9 minutes) administration; same plasma concentrations achieved after approximately 20 minutes

• onset of action markedly delayed following oral administration (66 minutes)

CRASH-2 identified an absolute reduction in all-cause mortality of 1.5% with TXA, with a number needed to treat [NNT] of 67, and a reduction in bleeding-related mortality of 0.8% (NNT 125) (e2). CRASH-3 found a reduction in head injury-related mortality of 1.3% (NNT 77) (e3). The analyses included in the present review, which employed different methodological approaches, reported – sometimes in subgroup analyses – an absolute reduction in mortality of

• up to 1% (15, 17)

• up to 2% (7, 11, 13, 20–22, 24, 28)

• up to 3% (7, 19, 25)

• up to 5% (2, 14).

Some of the included studies reported either unchanged (1, 3, 28) or even increased (1, 3, 5, 13, 17) mortality, mostly as a trend and without statistical significance (Table). TXA reduces mortality most markedly in the subgroup of patients with massive bleeding and shock. Thus, in the STAAMP trial, mortality among severely injured patients with a systolic blood pressure (SBP) of 70 mm Hg or less was 17% lower in those treated with TXA than in those without TXA (18.5% versus 35.5%, NNT 6) (e14). In the Cal-PAT trial, mortality among severely injured patients who received ≤10 units of total blood products was 14.7% lower with TXA (8.5% versus 23.2 %, NNT 7) (e15), and in the CRASH-2 trial mortality among those with an SBP ≤75 mm Hg was 4.5% lower (30.6% versus 35.1%, NNT 22) (e2). In the military MATTERs trial, overall mortality was 6.5% lower in the TXA group (17.4% versus 23.9%, NNT 15) and 13.7% among patients receiving massive transfusion (14.4% versus 28.1%, NNT 7) (e16). Since 2015, TXA has been recommended for use in the civilian setting only for severely injured patients in shock (e17). According to the current Clinical Practice Guideline, TXA is indicated for “patients with life-threatening hemorrhage and/ or in shock and in those with confirmed hyperfibrinolysis” (e4). TXA reverses hyperfibrinolysis, prolongs fibrinolysis suppression, and reduces early mortality (e5, e18). TXA is harmful in patients without hyperfibrinolysis (e19). TXA alone will not control severe hemorrhage when administered to treat patients with massive bleeding (e20, e21). A coagulation-independent effect, such as a reduction in the release of syndecan, has been suggested (e22).

Table. Included meta-analyses of RCTs on survival, neurological outcome, and thromboembolic risk^*1.

Reference	Studies	Main pat. characteristic	Outcome*2	Complication*3
Huang et al. 2022 (15)	13 RCTs (n = 18 675)	TBI	Mortality (overall) RR 0.99 [0.92; 1.06]	TE 2.3% vs. 1.9%; RR 1.05 [0.83; 1.33]
			GOS score <4 (unfavorable outcome) RR 0.96 [0.82; 1.11]
Germans et al. 2023 (16)	11 RCTs (n = 2717)	Aneurysmal SAH	Poor neurological outcome RR 1.03 [0.94; 1.13]
Xiong et al. 2023 (17)	25 RCTs (n = 20 146)	ICH	Mortality (ICH) OR 1.02 [0.84; 1.23]
			ICH: mRS ≤ 2 (favorable outcome) OR 1.05 [0.89; 1.24]
			Mortality (SAH) OR 0.84 [0.54; 1.31]	DVT (SAB) 1.8% vs. 1.7% OR 1.08 [0.51; 2.30]
			Mortality (TBI) OR 0.91 [0.69; 1.21]	PE (TBI) 0.6% vs. 0.6% OR 1.22 [0.45; 3.27]
Biffi et al. 2023 (18)	5 RCTs (n = 34 882) prehospital	Trauma with/ without TBI	24-hour mortality (overall) RR 0.83 [0.74; 0.95]
			28-day mortality (overall) RR 0.93 [0.88; 0.97]
Acharya et al. 2023 (19)	3 RCTs (n = 3081) prehospital	>80% blunt trauma	GOS-E score ≥ 5 (favorable outcome) RR 1.00 [0.93; 1.09]	TE 12.8% vs. 12.6% RR 1.04 [0.72; 1.49]
			24-hour mortality RR 0.73 [0.56; 0.96]
			28-day mortality RR 0.82 [0.69; 0.97]
Song et al. 2024 (20)	10 RCTs (n = 10 954)	TBI	Mortality RR 0.92 [0.85; 1.0]	PE 0.7% vs. 0.5% RR 1.33 [0.56; 3.15]
Fouche et al. 2024 (21)	7 RCTs (n = 32 832)	Trauma with/ without TBI	24-hour mortality (overall) OR 0.76 [0.65; 0.88]	TE OR 0.96 [0.73; 1.27]
			28-day mortality (overall) OR 0.89 [0.84; 0.95]
Zhang et al. 2024 (22)	11 RCTs (n = 11 299)	TBI	Mortality (overall) RR 0.93 [0.86; 1.00]	TE 2.0% vs. 2.1% RR 0.85 [0.68; 1.06]
			GOS score <4 (unfavorable outcome) RR 0.92 [0.78; 1.09]
Lee et al. 2025 (26)	25 RCTs (n = 16 677)	TBI	24-hour mortality (GCS score <9 or TXA <2 hours) RR 0.73 [0.64; 0.84]	TE RR 1.11 [0.97; 1.28]
			24-hour mortality (all others) RR 1.27 [0.94; 1.72]
Utsumi et al. 2025 (27)	10 RCTs (n = 11 237)	TBI	Mortality (TXA <3 hrs)	TE
			Placebo vs. 1 g bolus + 1 g/8 hrs: RR 1.10 [1.00; 1.21]	RR 1.26 [0.69; 2.30]
			Placebo vs. 2 g bolus: RR 1.66 [1.11; 2.46]	RR 0.87 [0.30; 2.52]
			1 g bolus + 1 g/8 hrs vs. 2 g bolus: RR 1.51 [1.01; 2.24]	RR 0.69 [0.23; 2.04]
Steiner et al. 2025 (28)	8 RCTs (n = 3061)	Stroke due to spontaneous ICH	7-day mortality OR 0.82 [0.63;1.07]	TE 4.7% vs. 4.0% OR 1.18 [0.82; 1.68]
			90-day mortality OR 1.00 [0.83;1.20]

^*1Always TXA vs. control. The primary outcome is printed in bold.

^*2RR or OR [95% CI]

^*3Frequency and RR or OR [95% CI]

GCS, Glasgow Coma Scale; GOS, Glasgow Outcome Scale (higher scores reflect better overall recovery; a score of 4 indicates a favorable outcome, defined as moderate neurological disability); GOS-E, Glasgow Outcome Scale – Extended (higher scores reflect better overall recovery; a score of 4 indicates a favorable outcome, defined as moderate neurological disability); hr, hour; HR, hazard ratio; ICH, intracranial hemorrhage; PE, pulmonary embolism; mRS, modified Rankin Scale (higher scores reflect worse outcomes; a score of 3 indicates that the patient requires assistance with daily activities); CI, confidence interval; n, sample size; OR, odds ratio; pats., patients; RCT, randomized controlled trial; RR, relative risk; SAH, subarachnoid hemorrhage; TBI, traumatic brain injury; TE, thromboembolism; DVT, deep vein thrombosis; TXA, tranexamic acid

Therapeutic time window for tranexamic acid

The optimal time for administering TXA appears to be within 90 minutes of injury. The CRASH-2 and CRASH-3 trials demonstrated a time-dependent effect of TXA, with a benefit when administered within three hours of injury and harm associated with later administration (e2, e3). A secondary analysis of CRASH-2 further narrowed the time window to within one hour of injury. This resulted in an absolute reduction in death due to bleeding by 2.4% (RR 0.68 [0.57; 0.82]; NNT 41), but an absolute increase by 1.3% when administered more than three hours after injury (RR 1.44 [1.12; 1.84]; number needed to harm [NNH] 76) (e23). Combined data from the CRASH-2 and WOMAN trials showed a 10% decline in the effectiveness of TXA for every 15-minute delay in TXA administration (e24). According to a reanalysis of data from CRASH-2 and CRASH-3 (n = 28 448), the relative risk reduction, irrespective of age and blood pressure, was greatest when TXA was administered within two hours of injury (24-hour mortality: RR 0.73 [0.64; 0.84]). Risk reduction declines rapidly beyond this time window. The greatest absolute risk reduction (24-hour mortality: –2.3 %) was observed in patients with a low blood pressure and a low Glasgow Coma Scale score when TXA was administered immediately after injury (13). Another analysis of this data showed that the beneficial effect on 24-hour mortality was greatest when administered within the first hour after injury (≤1 hour: OR 1.27 [1.03; 1.56]; 1–3 hours: OR 124 [105; 146]; >3 hours: OR 1.14 [0.90; 1.45]) (7). A systematic review article involving five RCTs evaluating prehospital TXA use found a clinically relevant reduction in 24-hour mortality in favor of TXA, corresponding to eight fewer deaths per 1000 TXA administrations; the effect was slightly smaller for 30-day mortality (Table) (18). A meta-analysis of three RCTs on prehospital TXA administration found lower risks of 24-hour and 28-day mortality, with no improvement in neurological outcomes (Table) (19). According to seven RCTs (n = 32 832), prehospital administration of TXA reduced the relative risk of death by 22% compared with placebo and by 9% with in-hospital administration (Table) (21). Another meta-analysis (2 RCTs, 9 cohorts; n = 1259) demonstrated a reduction in 24-hour mortality in all three analyses: in the overall analysis (OR 0.82 [0.71; 0.94]), in the analysis restricted to RCTs (OR 0.71 [0.52; 0.96]), and in the analysis restricted to cohort studies (OR 0.85 [0.72; 0.99]) (24). The results for 28-day mortality were not consistent (24). The PATCH-Trauma trial (n = 1310) found no difference in functional outcomes six months after injury between patients who did and those who did not receive prehospital TXA, although mortality was lower (2). In absolute terms, for every 100 patients treated with TXA, four extra patients were alive at six months; however, four extra patients were also classified as having suffered severe disability. A subgroup analysis of the prehospital STAAMP trial confirmed that the greatest survival benefit was achieved when TXA was administered within one hour of injury in severely injured patients with shock (18.5% versus 35.5%; RR 0.52 [0.34; 0.80]) (e14). A secondary analysis of the PATCH-Trauma trial (2) showed a reduction in the risk of death within 28 days after administration of TXA within 90 minutes (17% versus 25%; adjusted relative risk [aRR] 0.64 [0.50; 0.82]) (Figure 1) (14). In a secondary analysis of two trials (STAAMP, PAMPer) (e14, e25), the reduction in mortality at 24 hours was more pronounced after prehospital TXA administration (adjusted odds ratio [aOR] 0.42 [0.21; 0.83]) than after in-hospital administration (aOR 0,58 [0,19; 1,75]) (9). Furthermore, every one-minute delay was associated with an increase in the 24-hour mortality risk by 1.5% and a 2% increase in the 30-day mortality risk (9). In a secondary analysis (n = 1744) of the STAAMP (e14) and ROC-TXA trials (e26), the 28-day mortality risk was reduced after prehospital administration (adjusted hazard ratio [aHR] 0.72 [0.54; 0.96]) (11). Given the current evidence on the optimal time window for TXA administration, prehospital administration appears most appropriate and is largely consistent with common practice. For patients in shock, early administration within 90 minutes of injury – with timing being more important than location (e27) – enables targeted inhibition of the underlying pathophysiological mechanism (e21, e28).

Figure 1.

Effect of the time from injury to administration of TXA or placebo on 28-day mortality. An RR below 1 (thick grey line) indicates a benefit of TXA. (14) Licensed under the CC-BY 4.0 license, https://creativecommons.org/licenses/by/4.0 (Ali A et al.)

Dosage of tranexamic acid

The current recommendation is a single 1–2 g dose of TXA given at the earliest possible time (see the eResults section for supporting evidence).

Tranexamic acid in traumatic brain injury

The CRASH-3 trial investigated the effect of TXA in patients with traumatic brain injury (TBI). Altogether, more than 9000 patients were randomized and treated within three hours of injury in the placebo-controlled trial (e3). After exclusion of patients with a GCS score of three or less or bilateral unreactive pupils, the risk of head injury-related death was 12.5% in the TXA group versus 14% in the placebo group (RR 0.89 [0.80; 1.00]). The risk was reduced with TXA in patients with mild-to-moderate TBI (RR 0.78 [0.64–0.95]) but not in patients with severe TBI (RR 0.99 [0.91–1.07]). The following specific parameters of coagulation function were examined in patients with isolated TBI:

• thrombin-antithrombin III complexes as markers of fibrin production

• D-dimer as a marker of hyperfibrinolysis, and

• plasminogen activator inhibitor-1 (PAI-1) for impaired fibrinolysis (e36)

The plasma levels of all three parameters of patients in the group with poor outcome were elevated from arrival until seven days after injury (each p <0.001). There was considerable overlap evident in the time courses of the plasma levels, whereas isolated hyperfibrinolysis was detectable only early after injury and then only for a short period. Injured patients with TBI more commonly developed a fibrinolysis shutdown phenotype. (e37, e38). The timing of TXA administration appears to be even more crucial in patients with TBI (Table) (15). These are probably the reasons why meta-analyses have so far failed to show consistently positive effects of TXA in patients with TBI (13 RCTs, n = 18 675, and 11 studies, n = 1299; Table) (15, 22). Most meta-analyses show no improvement in neurological outcomes after administration of TXA (17, 20, 27, 28, e39–e41). In many of the study groups examined, the upper confidence interval limit for the RR exceeded the null value of one. That means the RR was not statistically significant, and TXA had a beneficial effect in only a small number of patients. A metaanalysis (n = 15 015) demonstrated a beneficial effect on 28-day mortality among patients with a GCS score above 9 (RR 0.71 [0.60; 0.85]; risk difference −1% [−0.8; +2.9]), not among those with a GCS score of nine or less, however (30). The prehospital 2 g bolus dose was associated with a marked survival benefit, particularly in CT-positive patients with TBI, compared with the standard dose (12). A benefit in neurofunctional outcome was evident in injured patients with an initial GCS score of less than 9 (RR 1.22 [0.89; 1.68]) (2). A secondary analysis excluding patients with unreactive pupils at baseline showed lower rates of progressive hemorrhage and the development of new hemorrhages over time (aRR 0.80 [0.66; 0.98]) (e42). Given the poor neurological outcome and the absence of a sustained reduction in mortality, many authors do not recommend routine TXA administration for intracranial hemorrhage (Table) (3, 16, 22, 28) or are explicitly against it (e43). In patients with isolated TBI and GCS scores ≤12, and especially those with bilaterally preserved pupillary reaction, prospective data and several recent meta-analyses, including subgroup analyses, indicate a possible survival benefit and reduced hemorrhage expansion (12, 20, 22, 30, e3, e26, e41). The administration of TXA may therefore be considered in these patients.

Tranexamic acid and the risk of developing thromboembolism

Although the safety profile of TXA is repeatedly emphasized, the risk of thromboembolism remains (Table) (8). The CRASH-2 trial (e2) with 20 211 participants reported a surprisingly low number of 369 thromboembolic complications (TXA: 168 = 1.7% versus NaCl: 201 = 2.0%). The authors assumed that complications were under-reported and that the incidence of TE was underestimated, so they did not rule out an increased risk of TE (e2, e44). In 2015, the study by Cole et al. led to TXA being recommended only for severely injured patients in the civilian setting who had a fourfold higher absolute rate of TE (2% versus 8%, p <0.01) (e17). Similarly, the CRASH-2 and CRASH-3 trials do not rule out an increased rate of TE, in addition to the possibility of underreporting. There, the confidence intervals included the null value of 1; for example, in CRASH-2 (e2), the RR for “death due to vascular occlusion” was 0.69 [0.44; 1.07] and the RR for “any vascular occlusive event” was 0.84 [0.68; 1.02]. In the CRASH-3 trial (e3), the corresponding parameters for “vascular occlusive events” were RR 1.13 [0.80; 1.59] after TXA administration within 3 hours of injury, RR 0.77 [0.49; 1.21] after TXA more than three hours after injury, and RR 0.98 [0.74; 1.28]) overall. The analyses included in the present article (using various methodologies) report an increased risk of thromboembolism (4, 6, 8, 23, 24, 26), with confidence intervals either above 1 (1, 2, 11, 14, 15, 17, 19, 20, 25, 26, 28, 29) or at least including 1 (7, 21, 22). This would seem inconsistent with the statement that there was no evidence of thromboembolic complications (e45, e46). A secondary analysis of the multicenter, double-blind RCT “Prehospital TXA for TBI” (e26) found a higher rate of deep vein thrombosis (DVT) after late prehospital administration (<45 minutes: 0.8% versus ≥45 minutes: 3.4%, p = 0.021) (e47). In a retrospective observational study of severely injured military personnel, there was an approximately ninefold increase in the rate of pulmonary embolism (2.7% versus 0.3%) and an approximately twelvefold increase in the rate of DVT (2.4% versus 0.2 %) among patients who received TXA (e16). The TAMPITI trial (8) found a dose-dependent risk of thromboembolic complications. In comparison with placebo, the adjusted hazard ratio was 3.20 [1.12; 9.11] for 2 g TXA and 5.33 [1.94; 14.63] for 4 g TXA. An analysis of the TraumaRegister DGU® (n = 37 342) also demonstrated a dosedependent rise in the risk of TE complications (one dose: aOR 1.56 [1.35; 1.81]; two doses: aOR 1.79 [1.43; 2.24]) (6). For injuries in the age group of 18- to 40-year-olds, there was a 1.65-fold increased risk of developing DVT and a 2.48-fold increased risk of pulmonary embolism after TXA (4). The risk of TE in patients with TBI was also increased when TXA was administered more than eight hours after injury. A similar increase was observed when treatment was continued for more than one day (Table) (26). A meta-analysis (n = 11 259) showed an approximately 20% relative increase in TE risk after prehospital TXA administration compared with no TXA administration (8.1% versus 6.7%; OR 1.22 [1.03; 1.44]). The increase in this risk was more pronounced in the RCTs (16.3% versus 12.7%; OR 1.33 [1.04; 1.70]) than in the cohort studies (5.3% versus 4.7%; OR 1.13 [0.90; 1.42]) (24). A metaanalysis of almost two million trauma cases found a 2.84-fold increase in the risk of VTE associated with TXA administration (23). Systematic screening for thromboembolic events was not reported in most publications; where such screening was performed, the incidence of TE was about twice as high (23, e48). Even for non-traumatic indications, the use of TXA is currently the subject of critical debate due to the risk of TE (e49). Overall, in patients without shock, the studies listed here report absolute risk differences for mortality ranging from −5% to 5% (5), and for thromboembolic adverse events from −0.2% to +4% (14). Since positive and negative effects occur with similar frequency, a careful assessment of potential benefits and potentially increased risk of TE is recommended for each patient before TXA administration (25, e50).

Conclusion

Figure 2 presents an algorithm for the pragmatic use of TXA. In light of recent findings, its broad, uncritical, and unselected use does not appear justified (e21). The optimal dose remains a matter of debate and is probably a single dose of 1 to 2 g for adults. The claim that there is no evidence of thromboembolic complications following TXA administration is no longer tenable.

Figure 2.

Algorithm for the pragmatic use of tranexamic acid in patients with (suspected) life-threatening hemorrhage

* Patients with severe TBI may also benefit from early administration of TXA (2, 27, e51); the benefit, however, has not been consistently shown across studies GCS, Glasgow Coma Scale;

ICH, intracranial hemorrhage;

BW, body weight;

SAH, subarachnoid hemorrhage;

TBI, traumatic brain injury;

TXA, tranexamic acid

eRESULTS SECTION

Dosage of TXA

The current dosage recommendations of 10 to 15 mg/kg are based on in-vitro studies of tPA-induced fibrinolysis (e29, e30). The standard regimen of 1 g loading dose of TXA followed by an infusion of 1 g over eight hours is derived from a 2007 Cochrane review of the perioperative use of antifibrinolytic agents (e31). A metaanalysis of patients with TBI demonstrated the lowest mortality with a dose of 2 g administered within three hours of injury (Table) (27). In a meta-analysis (20 trials; n = 12 523) 1 g was compared with ≥2 g and ≥30 mg/kg (e32): although the higher dose reduced transfusion requirements (OR 0.86 [0.76; 0,.97]; moderate certainty), it had no effect on blood loss (43.31 [135.53; 48.90] mL less; low certainty) and only an uncertain effect on mortality (OR 0.70 [0.37; 1.32], very low certainty). Multivariate regression analyses based on prospective data comparing 1 g bolus only, 1 g bolus plus 1 g infusion over eight hours, 2 × 1 g bolus, and 1 × 2 g bolus showed no independent dose effect on mortality (OR 1.32 [0.60; 2.92] versus 1 versus 0.89 [0.35; 2.26]) (10). Following prehospital administration of 1 g TXA, 220 patients in shock were randomized in a double-blind placebo-controlled RCT to receive either a second in-hospital dose of 1 g TXA or placebo(1). Twenty-four-hour mortality did not change in comparison with placebo (RR 1.00 [0.24; 4.02]) and even showed a trend towards lower 28-day mortality (27.6% versus 14.3%; RR 1.36 [0.93; 2.00]). Furthermore, the second TXA bolus had no effect on outcome; the Cal-PAT trial reached the same conclusion (e15). A secondary analysis (n = 1744) demonstrated a 22% relative reduction in the risk of mortality for each gram of TXA administered before hospital arrival (HR 0.78 [0.63; 0.96]) (11). A subgroup analysis of the “Prehospital TXA for TBI” trial (e26) evaluated prehospital TXA administration in CT-positive patients with TBI (12). Compared with the standard dose of 1 g followed by 1 g over 8 hours with placebo, a marked reduction in 28-day mortality was observed after a 2 g bolus administered before hospital arrival (2 g bolus: 18% versus standard regimen: 26% versus placebo: 27%; adjusted difference 2 g bolus versus standard regimen − 10.2 [−17.6; −2.9] and 2 g bolus versus placebo − 8.5 [−15.9; −1.0]). This finding resulted in an update of the UK NICE Guideline, with a conditional recommendation in favor of an early administration of a 2 g bolus for head injuries (e33). Post-hoc data from the TAMPITI trial showed that administration of a 2 g bolus maintained TXA concentrations of more than 10 mg/L for eight hours in 95% of cases (e34). Military guidelines recommend a prehospital bolus of 2 g, especially since trauma-center care cannot be guaranteed within the first hour (e35). The current recommendation for TXA dosing is a single dose of 1–2 g TXA administered as early as possible.

Questions on the article in issue 12/2026: Tranexamic Acid for Acute Bleeding in Severely Traumatized Patients

The submission deadline is 11 June 2027 Only one answer is possible per question.

Please select the answer that is most appropriate.

• Question 1

  How common is hyperfibrinolysis estimated to be in patients with severe trauma?

  1. 1/1 000 000
  2. 0.02%
  3. 1%
  4. 20%
  5. 50%

• Question 2

  What is the effect of tranexamic acid on acute hemorrhage?

  1. It blocks the conversion of plasminogen to plasmin and inhibits fibrinolysis.
  2. It is a recombinant clotting factor that promotes blood clotting.
  3. It increases the production of fibrin.
  4. It increases the effect of tPA.
  5. It prevents hypofibrinolysis.

• Question 3

  What are the pharmacokinetics of tranexamic acid (TXA)?

  1. The onset of action is approximately the same after intravenous, intramuscular, and intraosseous administration.
  2. The onset of action after intramuscular TXA administration is 1 to 2 hours.
  3. Intravenous administration is ineffective because TXA is immediately inactivated.
  4. Its elimination half-life is 24 to 30 hours.
  5. In patients with multiple injuries, the dose of TXA should be titrated according to plasma levels.

• Question 4

  Which dose of TXA is recommended for prehospital administration in patients with life-threatening hemorrhage?

  1. 2–4 mg intravenous
  2. 10–20 mg intravenous
  3. 0.5 g intravenous
  4. 1–2 g intravenous
  5. 4 g intravenous

• Question 5

  What absolute reduction of all-cause mortality was observed with TXA in the CRASH-2 trial?

  1. 25%
  2. 11%
  3. 5.5%
  4. 1.5%
  5. 0.2%

• Question 6

  In which clinical settings does tranexamic acid lower mortality most markedly?

  1. when bleeding does not cease spontaneously within 20 minutes
  2. in patients with primary blunt trauma
  3. in patients with stroke after spontaneous intracranial hemorrhage
  4. in patients with extensive burns
  5. in patients with severe hemorrhage and shock

• Question 7

  According to the studies and meta-analyses reported in the article (including subgroup analyses), by what order of magnitude does tranexamic acid reduce absolute mortality in severely injured patients with active bleeding who are not in shock?

  1. up to 0,5%
  2. up to 5%
  3. up to 15%
  4. up to 40%
  5. up to 80%

• Question 8

  A 35-year-old patient was involved in a road traffic accident and suffered severe hemorrhage associated with a systolic blood pressure of 70 mmHg. In an ideal setting, when should TXA be administered to reduce mortality?

  1. within 20 minutes of injury
  2. within 90 minutes of injury
  3. within 6 hours of injury
  4. within 24 hours of injury
  5. the time interval does not have any significant effect

• Question 9

  Which risk is associated with higher doses of TXA (for example, 4 g or more)?

  1. increased tendency to bleed
  2. increased risk of thromboembolic events
  3. reduced efficacy in the presence of hyperfibrinolysis
  4. increased mortality in patients with traumatic brain injury
  5. no known risks

• Question 10

  A patient with traumatic brain injury (TBI) receives treatment within two hours of injury. According to the CRASH-3 trial, which effect does TXA have in this case?

  1. It reduces all-cause mortality in patients with severe TBI (RR 0.71).
  2. It reduces mortality in patients with mild-to-moderate TBI (RR 0.78).
  3. An increased risk of thromboembolic events can be excluded.
  4. It has no impact on mortality.
  5. It improves the neurological outcome (RR 0.65).