The only FDA-approved usage for tranexamic acid (TXA) is for heavy menstrual bleeding and short-term prevention in patients with hemophilia.
Off-label uses of oral, topical, and intravenous TXA:
Intravenous TXA is commonly used in a severely bleeding patient requiring massive transfusion protocols (MTP) or when hyper-fibrinolysis is demonstrated. The most frequent sign is in trauma patients but may be utilized in any patient at significant risk of hemorrhage. The 2010 CRASH-2 trial was a multi-center randomized, double-blinded, controlled trial where patients either received TXA or a placebo in adult trauma patients with significant hemorrhage with systolic blood pressure less 90 mmHg, heart rate greater than 110 beats per minute, and within eight hours of injury. They found TXA to improve survival when administered within three hours of the injury in a patient population with significant hemorrhage.[4][5] The MATTERs trial followed this in 2011. This was a retrospective observational study looking to validate CRASH-2. Combat trauma patients requiring at least one unit of blood within 24 hours of presentation. The MATTERs trial revealed TXA decreased overall mortality, notably those requiring MTP. This is the only trial that has shown increased rates of thrombosis.[6] It should be noted that TXA is an antifibrinolytic and not a procoagulant.
Off-label intravenous uses of TXA are seen in surgical operations to reduce blood loss:
Other off-label intravenous TXA:
Non-traumatic subarachnoid hemorrhage: A randomized, prospective, multicenter study looking into the administration of TXA and reduction of rebleeding rates. Their data did reveal a reduction of rebleeding and mortality compared to the group not treated with TXA.[13]
Postpartum hemorrhage as represented in the study of the WOMAN Trial Collaborators in 2017, a large multicenter, randomized, controlled, double-blinded study showing TXA reduces death in women with postpartum hemorrhage if given as soon as possible after bleeding onset.[14]
Gastrointestinal bleeding: Past trials have showed a trend toward mortality reduction and less blood product use however these were based in concert with older therapies. Newer trials are underway to better understand the role of TXA in patients with gastrointestinal bleeding. [15][16][17]
Off-label oral TXA:
Post-procedural after cervical conization: A double-blind, randomized, controlled trial revealed that oral TXA regimen reduced post-procedural blood loss. TXA was also provided prophylactically, likewise, reducing blood loss compared to the placebo group.[18]
Hereditary angioedema (HAE): A systematic review of four medications given prophylactically to reduce HAE attacks. All four drugs, one being TXA, reduced the frequency of HAE attacks compared to a placebo.[19]
Transurethral retrograde prostatectomy (TURP): A prospective and randomized trial where TXA was given to the treatment group, 2 g TXA three times daily on the day of, and the first day after the operation. Their data revealed that short-term oral TXA reduced intra-operative blood loss during a TURP.[20]
Tooth extractions in patients on oral anticoagulants. A prospective random, controlled trial looking at a 2-day versus 5-day oral solution of TXA to prevent postoperative bleeding in patients on warfarin. The study showed that a 2-day regimen was equally effective as the 5-day course in preventing blood loss.[21]
Total unilateral hip replacement surgery: A double-blind, randomized, controlled trial of 161 patients undergoing unilateral primary total hip replacement investigated the effect of topical (intra-articular) application of TXA on blood loss showing that intra-articular TXA reduced the need for blood transfusion versus patients not receiving TXA.[22] Another study looked at intra-articular TXA vs. intravenous TXA, and the intra-articular was non-inferior to the intravenous form, thus recommending the continued use of the intra-articular administration.[23]
Off-label Topical TXA:
Traumatic hyphema: A multi-database review revealed that TXA reduces secondary hemorrhage in traumatic hyphema. It also reduced fibrinolysis of the clot and showed increased corneal staining.[24]
Nosebleed: Patients on antiplatelet agents as well as unmedicated patients with Nosebleeds treated with packing dipped in TXA, showed decreased bleeding, decreased rebleeding, decreased emergency department times and improved patient satisfaction.[25]
Hemoptysis: Nebulized TXA has been shown in case series to reduce hemoptysis. [26][27][28]
TXA is a synthetic reversible competitive inhibitor to the Lysine receptor found on plasminogen. The binding of this receptor prevents plasmin (activated form of plasminogen) from binding to and ultimately stabilizing the fibrin matrix.
TXA used for hereditary angioedema works by its indirect effect of reducing complement activation. By reducing plasmin activity, it reduces the consumption of C1 esterase inhibitor.
IV uses:
Oral Uses:
Other uses:
Adverse effects include seizures, headaches, backache, abdominal pain, nausea, vomiting, diarrhea, fatigue, pulmonary embolism, deep vein thrombosis, anaphylaxis, impaired color vision, and other visual disturbances.
Contraindications: Known allergy to TXA, intracranial bleeding, known defective color vision, history of venous or arterial thromboembolism or active thromboembolic disease. Greater than 3 hours from traumatic injury.
Cautions:
TXA is not well studied in the renally impaired. It is 95% excreted in urine, so renal dosing is recommended and judicious administration in patients with severe renal impairment.
No adjustments required in the hepatic impaired patient.
TXA is a pregnancy category B. No harm or small risk has been noted in animal studies, but no risk seen in human studies.
Exposure to the infant via breast milk: A prospective, controlled observational study showed that while the infant is likely exposed to some TXA via the mother's breast milk, it is in such low concentrations that they recommended continued usage of TXA in a lactating mother.[30]
Monitor hemodynamics and watch of thromboembolic events.
The half-life of TXA is 2 to 11 hours. The duration of action is 3 hours after the initial dose.
Even though TXA only has a few approved usages, it is a well-researched drug and has many uses to help reduce blood loss. It has a low side effect profile and is safe to administer in most instances.
TXA is often a clinician-driven decision in the acute setting with hemorrhagic shock or expected MTP activation. Studies have shown that if administered within one hour of injury, it decreases the relative risk of death from bleeding by 32%, and if given within 1 to 3 hours after injury, by twenty-one percent.
If clinically indicated to administer TXA, it is important to communicate with the team. Ensure the medical professional that is administering the drug knows to give via a slow intravenous push over 10 minutes.
Keep TXA in mind for patients that have religious concerns about blood transfusions. It is a possible option in the event of hemorrhage or before surgery where blood loss is expected to be high.
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