What is the dosage and administration protocol for Tranexamic Acid (TXA) in bleeding control?

From the Guidelines

Tranexamic acid (TXA) should be administered to bleeding patients as soon as possible, ideally within 3 hours of injury, at a loading dose of 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 hours. This recommendation is based on the most recent and highest quality evidence from the European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1. The guideline suggests that TXA be given as early as possible, if feasible en route to the hospital, and within 3 hours after injury.

The administration protocol for TXA in bleeding control typically involves a loading dose of 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 hours 1. This dosing regimen is supported by the CRASH-2 trial, which demonstrated a significant reduction in all-cause mortality and death due to bleeding with the use of TXA in trauma patients 1.

Key points to consider when administering TXA include:

• TXA should be given as soon as possible to bleeding patients, ideally within 3 hours of injury
• The loading dose is 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 hours
• TXA works by inhibiting plasminogen activation, which prevents the breakdown of blood clots and thereby reduces bleeding
• Side effects to monitor include nausea, vomiting, hypotension with rapid infusion, and rarely, seizures
• Contraindications include active thromboembolic disease, subarachnoid hemorrhage, and severe renal impairment

It is essential to note that the effectiveness of TXA decreases significantly after 3 hours of injury, and therefore, it should not be given more than 3 hours following injury 1. Additionally, the administration of TXA should not await results from a viscoelastic assessment 1.

In other clinical scenarios, such as post-partum haemorrhage, TXA is recommended to be given at a fixed dose of 1 g intravenously at 1 mL/min, with a second dose of 1 g intravenously if bleeding continues after 30 minutes, or if bleeding restarts within 24 hours of completing the first dose 1. However, in the context of trauma patients, the dosing regimen recommended by the European guideline should be followed 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION • Before Extraction: Administer 10 mg/kg actual body weight of Tranexamic acid injection intravenously with replacement therapy. (2.1) • After Extraction: Administer 10 mg/kg actual body weight 3 to 4 times daily for 2 to 8 days. Infuse no more than 1 mL/minute to avoid hypotension. (2.1). • Reduce the dosage for patients with renal impairment. (2.2,8.6)

Tranexamic Acid (TXA) can be taken for 2 to 8 days for bleeding control, with a dosage of 10 mg/kg actual body weight administered 3 to 4 times daily after extraction 2, 2, 3.

• The dosage should be reduced for patients with renal impairment.
• It is essential to infuse no more than 1 mL/minute to avoid hypotension.

From the Research

Dosage and Administration Protocol for Tranexamic Acid (TXA) in Bleeding Control

• The optimal dosage and administration protocol for TXA in bleeding control vary depending on the clinical context and the patient's condition 4, 5, 6, 7.
• Studies have shown that early administration of TXA is important for efficacy, particularly in trauma and postpartum hemorrhage 4.
• The dosage of TXA can range from 1-3 grams, and it can be administered orally, intravenously, or topically 6, 8.
• A systematic review and network meta-analysis found that TXA given intra-articularly and orally at a total dose of greater than 3g pre-incision, intraoperatively, and postoperatively ranked the highest in reducing the risk of allogeneic blood transfusion 6.
• Another study found that TXA reduces bleeding in patients with menorrhagia, and in patients undergoing various surgical procedures, including orthopedic, cardiac, and prostate surgery 7.

Timing of Administration

• The timing of TXA administration is crucial, and early administration is recommended to maximize its efficacy 4, 7.
• A study found that delayed administration of TXA for trauma events or postpartum hemorrhage can increase mortality 7.

Route of Administration

• TXA can be administered orally, intravenously, or topically, and the choice of route depends on the clinical context and the patient's condition 6, 8.
• Topical application of TXA has been shown to reduce bleeding and blood transfusion in surgical patients, with minimal systemic effects 8.

Safety Considerations

• TXA has been associated with an increased risk of seizures, particularly with high doses and in patients with brain injury or cardiac surgery 4, 7.
• There is also a theoretical concern about the risk of thromboembolic events with TXA use, although most trials have not shown a significant increase in this risk 4, 8.