Effects of Tranexamic Acid on Mortality and Blood Transfusion in Trauma Patients with Significant Hemorrhage: A Clinical Trial

Original article Advances in Bioscience & Clinical Medicine ISSN: 2203-1413 Vol.05 No.04 Effects of Tranexamic Acid on Mortality and Blood Transfusion in Trauma Patients with Significant Hemorrhage: A Clinical Trial Farzad Kakaei1, Peyman Virani1, Shahriar Hashemzadeh1, Sina Zarrintan1*, Samad Beheshtirouy2, and Touraj Asvadi1 1- Department of General Surgery, Tabriz University of Medical Sciences, Tabriz, Iran 2- Department of Cardiothoracic Surgery, Tabriz University of Medical Sciences, Tabriz, Iran Abstract Extensive hemorrhage is a significant cause of mortality in trauma patients. Tranexamic acid has been used for controlling bleeding in cardiovascular surgeries and dental manipulations in patients with hemophilia. However, in traumatic patients with bleeding, its use dates back to more recent years. This study aims to examine the effects of this drug on reducing mortality and blood transfusion rate in trauma patients with significant hemorrhage. A total of 60 patients with significant trauma-related hemorrhage (systolic blood pressure < 90 mmHg/heart rate > 110/min) from the emergency department of Imam Reza Hospital (Tabriz, Iran), were randomized in two groups. The case group received intravenous Tranexamic acid (1 g in 10 min and then 1 g over 8 h). The control group received placebo. Rate of transfusion and rate of one-month mortality were compared between the study groups. The mean ICU stay and overall hospitalization times did not have significant difference between two groups (p<0.05). Transfusion of packed cells was 6.03±1.50 and 6.03±1.22 units in case and control groups respectively. Transfusion of fresh frozen plasma (FFP) was 2.50±1.36 and 3.03±0.96 units in case and control groups respectively (p=0.09). Transfusion of platelets was 0.40±0.20 1.33±0.31 units in case and control groups respectively (p=0.01). Three patients (10%) in the case group and 4 patients (13.3%) in the control group were expired (p=0.50). Tranexamic acid is safe and effective in reducing platelet transfusion rate in patients with trauma-related significant hemorrhage. However, transfusion need and mortality would not reduce by its use in trauma patients. Key Words: Trauma; Hemorrhagic shock; Tranexamic Acid; Transfusion Corresponding author: Sina Zarrintan, MD Department General Surgery, Tabriz University of Medical Sciences, Tabriz, Iran E-mail: Receive date: 2017-06-02 | Accept date: 2017-09-19 | Publish date: 2017-10-01 DOI: 10.7575/aiac.abcmed.17.05.04.04 Australian International Academic Centre, Australia 24| P a g e Original article Advances in Bioscience & Clinical Medicine Introduction Trauma is the leading cause of mortality in 1-44 years-old population. Bleeding is a significant cause of death and complications in trauma patients (1). Hemostatic equilibrium is provided by processes of coagulation and fibrinolysis in traumatic patients (2). However, overactivation of fibrinolysis pathways could lead to uncontrolled hemorrhage and significant mortality (3). Hemorrhage control is achieved by surgical intervention, volume resuscitation and pharmaceutical therapies in traumatic patients. Anti-fibrinolytic agents have been successfully used to control bleeding in nontraumatic conditions. For instance, Aprotinin is an accepted drug for hemorrhage control in liver transplantation (4). However, use of antifibrinolytic agents in traumatic and traumarelated hemorrhagic shock is a novel strategy which could lessen mortality and morbidity (5, 6). A number of studies recommend that Tranexamic acid can be used safely in trauma patients to control hemorrhage and reduce mortality (7-10). It is essential that traumatic bleeding is controlled in first ours of patients’ admission (11, 12). Along with vital strategies of surgical interventions and volume resuscitation, antifibrinolytic agents could lessen the need for transfusion and reduce hemorrhage-related mortality (13-15). The effects of Tranexamic acid on reducing mortality in traumatic patients have been described by Shakur et al. and Morrison et al. in 2010 and 2012 respectively (16, 17). The equilibrium of coagulation and fibrinolysis may compromise in traumatic shock and trauma-related hemorrhagic shock (18-20). Moreover, transfusion-related complications such as transfusion reactions, acute lung injury etc. could further complicate trauma patients receiving blood products (21-24). Thus, Tranexamic acid would reduce transfusion needs and may decrease morbidity and mortality in traumatic patients in hemorrhagic shock (25-27). In the present study, we wanted to assess the effects of intravenous Tranexamic acid in reducing mortality and transfusion needs in trauma patients with significant hemorrhage. To our knowledge, this is the first study to investigate the effects of Tranexamic acid on bleeding control in Trauma patients in Iranian population. Methods In a randomized-controlled trial, we assessed the effects of Tranexamic acid on mortality and transfusion needs in traumatic patients with significant hemorrhage. The study was conducted at Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. The study period was 16 months from January 2015 to April 2016. The entire patients were selected from Tabriz Imam Reza Hospital. This hospital is a level one trauma center and is the main and referral trauma hospital in East Azerbaijan province. During the study period, trauma patients were assessed for eligibility by our inclusion and exclusion criteria. Sixty patients were selected and were allocated to case and control groups. Each group contained 30 patients. The inclusion criteria were patients between 15-50 years of age, systolic blood pressure (SBP) less than 90 mmHg or heart rate more than 110 per min or both, trauma to admission interval less than eight hours, and not being in need of emergent surgical intervention. The exclusion criteria were patients younger than 15 years of age, patients older than 50 years of age, having contraindication to receive Tranexamic acid (pregnancy, known thromboembolic events, defective color vision, history of vascular occlusive disease, hyper-coagulopathy, history of allergic reaction and history of angioedema), and being in need of emergent surgical intervention. Australian International Academic Centre, Australia 25| P a g e Original article Advances in Bioscience & Clinical Medicine Study patients were divided into two groups of case and control groups. Randomization was conducted by www.randomizer.org. Figure 1 illustrates the follow diagram for randomized allocation of patients during the study. We administered Tranexamic to patients of case group within eight hours from trauma. Tranexamic acid was administered in 1 g dose (two 500 mg vials) infused by 100 ml of saline. Then, another 1 g dose was administered during eight hours. Tranexamic acid vials were products of Caspian Tamin Company (Tranexip 500 mg; 5 cc vials). For the patients in control group, pl (...truncated)