In this episode, I’ll discuss when to use (and when not to use) tranexamic acid in critically ill patients.
Mechanism
Tranexamic acid is an antifibrinolytic agent. It forms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis. It also inhibits the proteolytic activity of plasmin.
It has been investigated for many potential uses in critically ill patients. In many cases, it has been found beneficial, and in some cases, tranexamic acid is not recommended due to lack of efficacy.
Scenarios where tranexamic acid is useful
Trauma
When given within 3 hours of injury, tranexamic acid reduces all-cause mortality in trauma patients. This data comes from the 2010 CRASH-2 study. The absolute mortality reduction is 1.5%, leading to a number needed to treat of 67. The patients that seemed to benefit most were those in severe shock as defined by an initial systolic blood pressure of 75 mmHg or less. The severe shock group had a 5% absolute reduction in mortality for a number needed to treat of 20.
In safety analysis, there was no difference in the rate of vascular occlusive or venous thrombotic events between the tranexamic acid group and controls.
The protocol for administering tranexamic acid in the CRASH-2 study was to give 1 g over 10 minutes intravenously, then an intravenous infusion of 1 g over 8 hours.
Intracranial hemorrhage due to plasminogen activators
In episode 150 I discussed treatment of intracranial hemorrhage due to the fibrin-selective plasminogen activators alteplase, reteplase, and tenectaplase. According to the 2015 Guidelines for Reversal of Antithrombotics in Intracranial Hemorrhage, tranexamic acid may be considered if the first line treatment of cryoprecipitate is not available. The guideline authors make this a conditional recommendation, based on very low-quality evidence. There is not sufficient data to suggest that tranexamic acid affects outcomes in patients with intracranial hemorrhage from thrombolytics. If given, the guideline authors recommend tranexamic acid 10–15 mg/kg IV over 20 min.
Scenarios where tranexamic acid is not useful
Acute hereditary angioedema
As a result of reducing plasmin activity, tranexamic acid also reduces activation of complement. This is thought to result in decreased inflammation associated with hereditary angioedema.
Unfortunately, in an acute attack tranexamic acid provides minimal, if any, benefit. First line therapies should be used instead such as C1 inhibitors, icatibant, or ecallantide.
Acute upper GI bleeding
Early trials suggested that tranexamic acid had a beneficial effect in patients with acute upper GI bleed. In a meta-analysis, when only studies that examined tranexamic acid with modern GI bleed care such as proton pump inhibitors and endoscopy were considered, tranexamic acid had no beneficial effect.
Traumatic hyphema
Traumatic hyphema is when blood enters the anterior chamber of the eye as a result of a blunt or penetrating injury. Although previously recommended for use in traumatic hyphema, a meta-analysis has shown no significant beneficial effect of tranexamic acid in this patient population. In fact, patients with traumatic hyphema who receive an anti-fibrinolytic take a day longer for their hyphema to clear.
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