Tranexamic acid, an antifibrinolytic agent given intravenously, is indicated for the prevention of bleeding in hemophilia (over a short term), and during or after tooth extraction to reduce or prevent hemorrhage. Recently, the oral form of the drug received the FDA approval for the treatment of menorrhagia. Its successful use in controlling bleeding in these conditions has prompted researchers to study the efficacy of the drug in trauma patients. A large randomized placebo-controlled trial has demonstrated that a short course of intravenous tranexamic acid reduces mortality in bleeding trauma patients by about one-sixth. The study has been published in the latest issue of The Lancet.
Haleema Shakur, chairperson of the trial coordination for Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage 2 (CRASH 2), along with investigators from 40 other countries conducted the study on 20,211 adult trauma patients with significant bleeding or at an increased risk for the same. Systolic blood pressure <90 mm Hg or pulse rate of >110/min, or both was considered as significant bleeding. Within 8 hours of the accident, they were randomly allocated either to tranexamic acid (loading dose of 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 h) or placebo (0.9% saline). A total of 10,060 and 10,067 patients administered with tranexamic acid and placebo, respectively, were analyzed. The primary outcome measure was death in the hospital within 4 weeks of trauma, due to vascular occlusion (stroke, myocardial infarction, and pulmonary embolism), bleeding, head injury, multiorgan failure, and other reasons.
It was observed that tranexamic acid significantly decreased the all-cause mortality in 14.5% patients in the tranexamic acid group vs. 16.0% in the placebo group (relative risk=0.91; 95% CI=0.85-0.97; P=0.0035) and the risk of bleeding-associated death in 4.9% in the tranexamic acid group vs. 5.7% in the corresponding group (RR=0.85; 95% CI=0.76-0.96; P=0.0077). The number of deaths due to vascular occlusion were 0.3% in the treatment group and 0.5% in the placebo group. Deaths due to head injury, multi-organ failure, or other causes did not vary significantly between the two groups. No drug-related adverse effects were reported during the study. These findings indicate that tranexamic acid administered early reduces bleeding in trauma patients.
According to the World Health Organization, the annual global mortality from injuries is estimated to be five million in the developing nations. An inadequate healthcare system and an inefficient social welfare infrastructure further add to the impact. Most often, young adults are affected leading to a loss of income and heavy economic burden on the family. Tranexamic acid may prove to be an inexpensive and easily available treatment option in such injured bleeding patients.
1. CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32.
2. Cyklokapron [package insert]. New York, NY. Pfizer Inc; 2008.
3. Gosselin RA, Spiegel DA, Coughlin R, Zirkle LG. Injuries: the neglected burden in developing countries. Bull World Health Organ. 2009 Apr;87(4):246-246a.
4. Simple injection could save the lives of thousands of accident victims worldwide. London School of Hygiene and Tropical Medicine. Press Release. Last accessed July 26, 2010.