Shock Syndromes II

ii.

The number needed to treat is 67, and no difference between groups was noted in the risk of

vascular occlusive events.

iii.

In a separately published exploratory analysis, the greatest benefit for tranexamic acid occurred

with administration within 3 hours of injury (RR 0.68 1 hour or less from injury; 95% CI,

0.57–0.82; p<0.0001; RR 0.79 1–3 hours from injury; 95% CI, 0.64–0.97; p=0.03), with an

increased risk of death from bleeding after 3 hours from injury (RR 1.44; 95% CI, 1.12–1.84;

p=0.004).

iv.

Major limitations of this trial were that few patients were enrolled from regions with modern

trauma systems (e.g., blood product availability, MTP), and the baseline mortality was higher

than expected in North America or Europe.

CRASH-3 trial:

Evaluated the effects of tranexamic acid (same dosing regimen as used in CRASH-2) in

patients with traumatic brain injury. Patients were enrolled within less than 3 hours of injury

with either Glasgow Coma Scale (GCS) score less than 13 or intracranial hemorrhage on CT

scan and no major extracranial bleeding.

ii.

There was no difference in head injury–related death within 28 days with tranexamic acid

(18.5%) compared with placebo (19.8%) (RR 0.94; 95% CI, 0.86–1.02).

iii.

Tranexamic acid reduced death in patients with mild to moderate TBI, GCS 9–15 (RR 0.78;

95% CI, 0.64–0.95), but not in patients with a severe head injury, GCS 3–8 (RR 0.99; 95% CI,

0.91–1.07) who already had extensive intracranial hemorrhage before treatment.

iv.

Patients in CRASH-3 were sicker than those in CRASH-2, with head injury–related death 12%

in CRASH-2 versus 19% in CRASH-3.

study, tranexamic acid was associated with a 6.5% absolute reduction in in-hospital mortality for all

patients. A 13.7% absolute reduction occurred in those requiring massive transfusion, suggesting a

greater benefit in those with a higher severity of injury.

In the MATTERs II trial, adding fibrinogen (cryoprecipitate) to tranexamic acid further improved

in-hospital mortality compared with tranexamic acid alone (11.6% vs. 18.2%; p=0.03).

In trauma, tranexamic acid has not been shown to decrease the need for transfusion.

Recommendations related to tranexamic acid use in trauma:

When given, should be administered as early as possible to a trauma patient with bleeding

or within 3 hours of injury to a patient at risk of significant hemorrhage. Administered as a

loading dose of 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over

8 hours

ii.

Some hospital systems have begun giving the tranexamic acid loading dose prehospital to

prevent full activation of fibrinolysis, with improved outcomes when the loading dose was

given within 1 hour of injury. This strategy requires validation in a clinical trial.

iii.

Additional safety concerns have been identified related to tranexamic acid in trauma patients.

thrombotic events, including PE and venous thromboembolism (MATTERs trial).

suppressed fibrinolysis associated with high mortality from multiorgan failure.

iv.

Because of criticisms of previous trials and potential safety concerns, some experts advocate

the use of tranexamic acid only in select patients having a diagnosis of hyperfibrinolysis, but

no study on selective use of tranexamic acid has shown improved outcomes.

In the United States, the Eastern Association for the Surgery of Trauma (EAST) guidelines for

DCR conditionally recommended tranexamic acid as a hemostatic adjunct in severely injured

trauma patients.