Intravenous Tranexamic Acid Use in Elective Total Joint Arthroplasty

Patients undergoing major orthopaedic surgery procedures have increased risk of perioperative bleeding leading to transfusion. In the past, a number of protocols and techniques have been employed to minimize this risk:

• Use of controlled intraoperative hypotension
• Hemodilution
• Blood salvage systems
• Autologous blood donation ^2-5

Recently, there has been increased interest in the use of antifibrinolytics, such as tranexamic acid (TXA), that minimize bleeding through the inhibition of clot degradation. The purpose of this article is to review intravenous TXA use in total joint arthroplasty (TJA).

Mechanism of Action

Tranexamic acid, a synthetic analogue of the amino acid lysine, acts by competitively blocking the lysine binding site of plasminogen, which leads to inhibition of fibrinolysis.^1,6 Tranexamic acid enters the extravascular space and accumulates in tissues for up to 17 hours. The basis for its efficacy is thought to be the inhibition of tissue fibrinolysis and the consequent stabilization of clots.

Intravenous Dosing Schedules

A number of dosing schedules for the use of intravenous TXA have been described, such as an initial bolus of TXA followed by a 6-12 hour infusion or multiple intravenous bolus doses. Kagoma et al recently reviewed 21 papers on the use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery. The TXA dose ranged from 10-2 0mg initial bolus followed either by an infusion of 1-10 mg/kg/hr for 4-30 hours or repeated doses of the initial TXA dose every 3 hours for 1-4 doses.

These dosing schedules are somewhat cumbersome and labour-intensive, making them difficult to introduce into a busy operating room schedule and orthopaedic service. Moreover, such complex dosing schedules may not be required to achieve the desired effect when using TXA. In a recent meta-analysis, Cid et al showed that the efficacy in reducing the risk of receiving a blood transfusion was independent of the total TXA dose given.

The most commonly prescribed dose of TXA in the literature was 10 mg/kg initial bolus dose followed by a second similar dose at 3 hours. Our institution adopted a single dose of 20 mg/kg timed to be given prior to the onset of fibrinolysis. Use of this protocol at our institution has reduced the perioperative decrease in haemoglobin and red blood cell transfusion rates in patients having total knee arthroplasty and total hip arthroplasty compared with those of a similar cohort of patients in whom the protocol was not used. This weight-increment dosing facilitated pharmacy drug preparation, led to minimal dose variability and wastage, and resulted in a substantial estimated cost savings.

Tranexamic Acid Use in TJA

Multiple published articles have evaluated the use of TXA in primary TJA populations, including retrospective cohort studies,^9-11 randomized controlled trials,^12-18 and meta-analyses.^7,8,19 The use of TXA in these studies resulted in decreased blood loss and reduced transfusion requirements in TJA populations (Table 1).

Table 1. Studies Using Tranexamic Acid in Hip and Knee Arthroplasty

TXA = tranexamic acid, RCT = randomized control trial, THA = total hip arthroplasty, VTE = venous thromboembolic events, TKA = total knee arthroplasty, DVT = deep vein thrombosis

There did not appear to be in an increased incidence of thromboembolic events associated with TXA use. However, as noted by Kagoma et al, variation in dosing schedules and small study numbers indicate that a large randomized controlled trial is warranted to evaluate blood loss transfusions and thrombolytic complications using TXA in TJA.

Summary

Tranexamic acid has been shown to reduce bleeding and transfusion requirements without increasing the risk of thromboembolic events in patients undergoing TJA. However, there is still a need for an adequately powered prospective study to properly examine the safety and efficacy of this drug.

References

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Reprinted with permission from the Summer 2011 issue of COA Bulletin