Effect of Tranexamic Acid on Prevention of Hemorrhagic Mass Growth in Patients with Traumatic Brain Injury

Background

Intracranial hemorrhage is a common complication of traumatic brain injury (TBI). The purpose of this study is evaluation of the effect of tranexamic acid (TXA) on hemorrhagic mass growth in TBI patients.

Patients and Methods

In this randomized, double-blind clinical trial, 149 patients with TBI and any kind of blood on their computed tomography scan enrolled in the study and were randomly allocated to receive TXA or placebo. After 24 hours, computed tomography scan was repeated for assessing the changes in hemorrhage, new bleeding, and mass effects of blood on brain tissue. The primary outcome was growth of the hemorrhagic lesion. Data were analyzed by SPSS software using Fisher exact, chi-square, and Mann-Whitney U tests, as well as linear and logistic regression models.

Findings

The incidence of hemorrhagic lesion growth was 20.5% in the TXA group and 22.7% in the placebo group. The difference was not significant (P = 0.87, RR = 0.89). The mean (standard deviation) of hemorrhagic lesion growth was 9.4 (15.3) in the TXA group and 10.2 (10.1) in the placebo group without significant difference (P = 0.27). The frequency of deaths (2.7% vs. 4%), adverse outcome at discharge (10.8% vs. 17.3%), and 3 months later (6.8% vs. 14.7%) in the TXA group were lower than the placebo, but the difference was not statistically significant. No side effect was observed with the administration of TXA.

Conclusion

Administration of a short dose of TXA does not lead to significant prevention of growth of posttraumatic hemorrhagic lesion or improvement of clinical outcomes.

Introduction

Traumatic brain injury (TBI) is one of the major causes of death and disability in the world. It is estimated that 1.5 million patients die annually due to TBI.¹ The annual incidence rate of TBI in the United States is between 180 and 250 per 100,000 population,² and this figure is calculated between 15.3 and 144 per 100,000 population in Tehran, Iran.³ TBI is classified into 3 categories based on the Glasgow Coma Scale (GCS): severe (10%); moderate (10%); and mild (80%).⁴

Intracranial hemorrhage (ICH) is a common complication of TBI, which may progress and worsen after admission to the hospital.⁵ About three fourths of patients with TBI have intracranial hemorrhage,⁶ which may get larger while admitted to the hospital in about half of patients.7, 8 It is told that this bleeding is associated with a high risk of coagulopathy, and this may lead to increase in hemorrhage size, higher mortality, and disability. Increase in fibrinolysis, which implies high levels of fibrin degradation products, is a common pattern of coagulopathy in TBI. Therefore antifibrinolytic agents such as TXA may reduce ICH due to trauma.⁵

Several clinical trials have confirmed the efficacy and safety of TXA.9, 10, 11 In CRASH-2, an international study on the effects of TXA, 20,211 cases of trauma in 40 countries received an early injection of TXA. This resulted in reduced mortality of those who bled or were at risk of bleeding without any side effects. The researchers also concluded that TXA is a cost-beneficial drug in low- and middle-income countries.⁹ Later, this drug joined the World Health Organization's list of essential medicines.¹²

TXA administration in patients with aneurysmal subarachnoid hemorrhage has reduced the chance of rebleeding but increased brain ischemia probably due to vasospasm or microvascular thrombosis.¹³ Because many patients with trauma-related bleeding also have TBI, there will be apprehension about the risk of brain ischemia for these patients.⁵ Another study in nontraumatic intracerebral hemorrhages showed that TXA is effective in stabilizing the hematoma.¹⁴ Studies about TXA and TBI are limited. A subgroup of the CRASH-2 study including 270 cases with TBI had ICH, and their mean hemorrhagic growth was lower in the TXA in comparison with the placebo group, although the difference was not statistically significant. It was also found that TXA had no effect on mortality and disability of these patients.⁵ Yutthakasemsunt et al,¹¹ in a study of 238 patients with severe and moderate TBI, concluded that the difference between the 2 groups was not significant for progressive ICH, mortality, and unfavorable outcome. Jokar et al¹⁵ concluded in their study that in spite of an increase in bleeding volume in both the TXA and placebo groups, the increment in the TXA group was significantly lower than the control. In a systematic review of CRASH-2 and the Yutthakasemsunt study, it was concluded that TXA significantly reduced the progression of ICH and improved the clinical outcomes of patients. Finally, in this study, the researchers suggested that more studies and evidence were needed to support the routine use of this drug in TBI patients.¹⁶

Therefore due to limited studies about the effect of TXA on TBI-induced bleeding and the various effects of this drug on the outcomes of traumatic patients, this study was conducted to investigate the effect of TXA in prevention of increase in bleeding volume in TBI patients. If its effect was proven, it could be used as one of the routine drugs in the trauma emergency ward for reducing the mortality and morbidity of TBI.