Does Tranexamic Acid Treatment of Acute Intracerebral Hemorrhage Cause Ischemic Stroke?

Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York Presbyterian/Weill Cornell Medical College

SOURCE: Pszczolkowski S, Sprigg N, Woodhouse LJ, et al. Effect of tranexamic acid administration on remote cerebral ischemic lesions in acute spontaneous intracerebral hemorrhage: A substudy of a randomized clinical trial. JAMA Neurol 2022;79:468-477.

Acute spontaneous intracerebral hemorrhage is one of the least treatable forms of stroke. New therapies are needed. Antifibrinolytic treatments to reduce hematoma growth have been tried for decades but were abandoned after a negative study with activated factor VIIa, which was complicated by an excessive number of thromboembolic events, including myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism.¹

More recently, tranexamic acid has been tried in several recent randomized clinical trials. Tranexamic acid is a synthetic lysine analog that binds to plasminogen and prevents the interaction of plasminogen with fibrin, thereby inhibiting the dissolution of the intracranial blood clot. There is considerable experience with this medication that results in a reduced risk of death from bleeding in traumatic and postpartum hemorrhage. It now is being studied as a hemostatic agent in spontaneous intracerebral hemorrhage. However, similar to the use of other antifibrinolytic drugs, there is concern that there may be ischemic complications from this treatment, including ischemic stroke.

In patients with acute spontaneous intracerebral hemorrhage, approximately 20% of individuals develop diffusion-weighted positive hyperintensities that are spatially remote from the site of the hemorrhage and may represent small infarcts. These lesions usually are asymptomatic, but they have been associated with worse three-month outcomes, as well as lower Glasgow Coma Scale scores on hospital admission. Therefore, there is concern that the use of tranexamic acid may increase the risk of subsequent ischemic lesions in the brain. This study was undertaken to evaluate the frequency and risk of new diffusion-weighted imaging (DWI)-positive lesions in patients treated with tranexamic acid.

This prospective magnetic resonance imaging (MRI) substudy of a randomized clinical trial studying the effects of tranexamic acid for hyperacute primary intracerebral hemorrhage was conducted at follow-up 90 days after patients were randomized to receive either tranexamic acid or placebo. The number of DWI lesions remote from the hemorrhage were analyzed by three different neuroradiologists, and the number of lesions was compared between the treatment groups using logistic regression adjusted for baseline covariates.

A total of 219 participants were included who had available brain MRI data. Ninety-six were randomized to tranexamic acid and 123 were randomized to placebo. There were no baseline differences in clinical or demographic characteristics between the groups. There was no increase found in the number of DWI hyperintense lesions in the tranexamic acid group compared to the placebo group. There was no difference in the mean number or size of the lesions.

Participants who were randomized within three hours of onset of their hemorrhage or those who had chronic infarcts at presentation were less likely to have new DWI hyperintensities. Patients who had probable cerebral amyloid angiopathy appeared to have more DWI hyperintensities, but the numbers were small and not statistically significant. Overall, this study found no evidence of an increased number of remote ischemic lesions after treatment with tranexamic acid for acute spontaneous intracerebral hemorrhage, and studies with this agent will be ongoing.

REFERENCE

1. Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008;358:2127-2137.