Intravenous Tranexamic Acid Use in Elective Total Joint Arthroplasty

James L. Howard M.D., MSc, FRCSC
Douglas D. Naudie, M.D., FRCSC
London, ON

Patients undergoing major orthopaedic surgery procedures have increased risk of perioperative bleeding leading to transfusion1. In the past, a number of protocols and techniques have been employed to minimize this risk. This has included the use of controlled intraoperative hypotension, hemodilution, blood salvage systems as well as autologous blood donation2-5. Recently, there has been increased interest in the use of antifibrinolytics, such as tranexamic acid, that minimize bleeding through the inhibition of clot degradation. The purpose of the current article is to review intravenous tranexamic use in total joint arthroplasty.

 

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 fibrinolysis1;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 clots1.

Intravenous Dosing Schedules
There have been a number of dosing schedules described for the use of intravenous tranexamic acid7. These have included schedules of either an initial bolus of TEA followed by a 6-12 hour infusion or multiple intravenous bolus doses. A recent review of the use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopaedic surgery was performed by Kagoma et al.7 who studied 21 papers. The dose of TEA ranged from 10-20mg initial bolus followed either by an infusion of 1-10mg/kg/hr for 4-30 hours or repeated doses of the initial dose of TEA every three 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, these complex dosing schedules may not be required to achieve the desired effect when using tranexamic acid. In a recent meta-analysis, Cid et al.8 showed that the efficacy in reducing the risk of receiving a blood transfusion was independent of the total dose of TEA given. As the most commonly prescribed dose of TEA in previous literature was 10mg/kg initial bolus dose followed by a second similar dose at three hours, our institution adopted a single dose of 20mg/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 TKA and THA compared with those of a similar cohort of patients in whom the protocol was not used9. 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 Total Joint Arthroplasty
There have been multiple published articles evaluating the use of tranexamic acid in primary total joint arthroplasty populations. These have included retrospective cohort studies9-11, randomized controlled trials12-18, as well as meta-analysis7;8;19. The use of tranexamic acid in these studies resulted in decreased blood loss and reduced transfusion requirements in total joint arthroplasty populations (Table 1). There does not appear to be in increased incidence in thromboembolic events associated with tranexamic acid use. However, as noted by Kagoma et al.7 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 tranexamic acid in total joint arthroplasty.

Naudie_Table_1

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

References

 

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