IV Tranexamic Acid Prior to Hysterectomy for Reduction of Intraoperative Blood Loss: A Randomized Placebo-Controlled Trial

Tranexamic acid (TXA) is a synthetic lysine analog that inhibits plasmin fibrinolysis. It may be administered orally, intravenously, or topically, with a rapid onset of action (tmax = appx 3 hours) and 11-hour half-life. It is 6 to 10 times more potent than aminocaproic acid, another commonly used synthetic antifibrinolytic agent. Typical IV dosing is 10 mg/kg followed by infusion of 1mg/kg/hour, or simply 1g intravenously in one dose.

The efficacy of tranexamic acid in control of hemorrhage in trauma patients has been reported extensively. The CRASH-2 trial collaborators randomized 20,211 adult trauma patients with significant bleeding or at risk of significant bleeding within 8 hours of injury to IV tranexamic acid or placebo. All-cause mortality was significantly reduced with tranexamic acid (RR .91; p = .0035). Additionally, risk of death due to bleeding was significantly lower in those receiving tranexamic acid (RR .85; p = .0077). No differences in risk of vascular occlusive events were noted. Further analysis revealed reduced risk of death from bleeding if TXA was given within 3 hours of injury; treatment administered after 3 hours from injury increased the risk of death due to bleeding.

Administration of TXA during elective surgery has also been investigated. A 2011 systematic review of 252 randomized trials of patients undergoing elective surgery across disciplines included administration of TXA, aminocaproic acid, and aprotinin. TXA administration reduced the risk of transfusion peri-operatively (RR .61). A 2012 meta-analysis of TXA use in both elective an emergency surgery revealed that TXA reduced the risk of transfusion by one-third. The effect of TXA on risk of myocardial infarction, deep vein thrombosis, and pulmonary embolism was not statistically significant.

The utility of TXA appears to extend to obstetric hemorrhage. Several published studies exist analyzing its use in prevention of postpartum hemorrhage, though the drug is not considered standard for prevention or treatment of this condition. A pilot randomized open-label trial of IV TXA in women with postpartum hemorrhage over 800cc reported a lower median blood loss between groups, though the effect was modest. Additionally, significantly fewer women in the TXA group required transfusion or invasive procedures. A recent Cochrane review reports on twelve trials of low risk women undergoing cesarean section or spontaneous birth who received uterotonics with or without the addition of TXA. TXA was effective in decreasing estimated blood loss over 1 liter in women undergoing cesarean section. Mean blood loss was significantly lower in women receiving TXA (mean difference -77.79mL); effect was similar for women undergoing cesarean section and vaginal birth. Finally, the WOMAN trial is a large, ongoing, placebo-controlled trial examining the effect of early TXA administration in clinically diagnosed postpartum hemorrhage.

The use of TXA in the management of acute and abnormal uterine bleeding has been reported, and is FDA-approved for treatment of menorrhagia. One randomized study of oral TXA in the treatment of ovulatory menorrhagia reported a 45% decrease in mean menstrual blood loss with use of TXA as compared with placebo. Other studies have echoed these findings, with TXA more effective than NSAIDs but less effective than the levonorgestrel intrauterine device (IUD) in decreasing menstrual blood loss. More recently, a double-blind, placebo-controlled randomized-controlled trial (RCT) confirmed a significant decrease in menstrual blood loss(mean -69cc), improvements in social/physical limitations caused by menorrhagia and self-perceived menstrual blood loss. No data exist examining the efficacy of IV TXA in the management of acute or severe uterine bleeding.