Intravenous Tranexamic Acid Use in Elective Total Joint Arthroplasty

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Patients undergoing major orthopaedic surgery procedures have increased risk of perioperative bleeding leading to transfusion.1 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.1

Intravenous Dosing Schedules

A number of dosing schedules for the use of intravenous TXA have been described,7 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.7 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.8

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.9 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

Study

Study Design

Patients

TXA dose

Blood loss and transfusion

Risk of VTE

Johansson T et al,  2005 [12]

Double blind RCT

100 THA

15mg/kg

Reduces blood loss and transfusion requirements

No VTE complications

Niskanen RO and Korkola OL, 2005 [13]

Double blind RCT

39 cemented THA

10mg/kg and 2 8-hour intervals afterwards

Significant reduction in blood loss and transfusion requirements

No VTE complications

Cid J and Lozano M, 2005 [8]

Meta-analysis (9 RCTs though  2004)

9 RCTs for TKA

Low dose
(15-35mg/kg)
High dose (135-150mg/kg)

Significantly reduced the number of patients requiring RBC and the risk of being transfused

8 of 9 studies reported use of DVT prophylaxis.
No analysis of DVT rates between groups

Gill JB and Rosenstein A, 2006 [19]

Meta-analysis

13 RCTs
for THA

10-19mg/kg with or without infusion of 1mg/kg/hr

Significantly reduces both intraoperative and total blood loss, but only a trend towards reduction in transfusion

No difference in VTE rate compared to placebo

Orpen NM et al, 2006 [14]

Double-blind RCT

29 TKA

15mg/kg

Significant decrease in blood loss in early post-op period

No evidence of DVT with Duplex ultrasound

Camarasa MA et al, 2006 [15]

Double-blind RC00T

127 TKA

10mg/kg and 3 hours later

Significant decrease in blood loss, and nearly 80% reduction in transfusion rate

No VTE identified by clinical assessment

Molloy DO et al, 2007 [16]

RCT

150 TKA

500mg 5 mins prior to tourniquet and 3 hours later

Reduction in blood loss and transfusion requirements compared to control group

No VTE identified by clinical assessment in TEA group

Claeys MA et al, 2007 [17]

Double blind RCT

40 THA

15mg/kg

Significant reduction in total blood loss and transfusion requirements

Higher DVT by U/S in TEA group

Alvarez JC et al, 2008 [18]

Double-blind RCT

95 TKA

10mg/kg  then  1mg/kg per hour infusion

25% reduction in total blood loss; significant reduction in transfusion requirements

No VTE seen in either study group

Lozano M et al, 2008 [11]

Retrospective trial

414 TKA

10mg/kg  before and after tourniquet

Perioperative blood loss was significantly lower in TEA group; reduced transfusion requirements

No increase in VTE using contrast venography

Rajesparan K et al, 2009 [10]

Retrospective study

73 THA

1g IV  at induction

Significant reduction in blood loss and transfusion requirements

No increased incidence of DVT

Kagoma YK et al, 2009 [7]

Meta-analysis (1966-2007)

29 RCTs
for THA and TKA

10-15mg/kg

Statistically significant reduction in blood loss and transfusion requirements

No difference in VTE rates between groups

Ralley F et al, 2010 [9]

Retrospective cohort

493 both THA and TKA

20mg/kg

Significant reduction in blood loss and transfusion requirements

No difference in VTE rates between groups

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,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 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

  1. Eubanks J.D. Antifibrinolytics in major orthopaedic surgery. The Journal of the American Academy of Orthopaedic Surgeons. 2010 Mar ;18(3):132-8.
  2. Tenholder M., Cushner F.D. Intraoperative blood management in joint replacement surgery. Orthopedics. 2004 Jun ;27(6 Suppl):s663-8.
  3. Meert K.L., Kannan S., Mooney J.F. Predictors of red cell transfusion in children and adolescents undergoing spinal fusion surgery. Spine. 2002 Oct 1;27(19):2137-42.
  4. Murray D.J., Forbes R.B., Titone M.B., Weinstein S.L. Transfusion management in pediatric and adolescent scoliosis surgery. Efficacy of autologous blood. Spine. 1997 Dec 1;22(23):2735-40.
  5. Copley L.A., Richards B.S., Safavi F.Z., Newton P.O. Hemodilution as a method to reduce transfusion requirements in adolescent spine fusion surgery. Spine. 1999 Feb 1;24(3):219-22; discussion 223-4.
  6. Astedt B. Clinical pharmacology of tranexamic acid. Scandinavian journal of gastroenterology. Supplement. 1987 Jan ;13722-5.
  7. Kagoma Y.K., Crowther M.A., Douketis J., Bhandari M., Eikelboom J., Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thrombosis research. 2009 Mar ;123(5):687-96.
  8. Cid J., Lozano M. Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials. Transfusion. 2005 Aug ;45(8):1302-7.
  9. Ralley F.E., Berta D., Binns V., Howard J., Naudie D.D.R. One intraoperative dose of tranexamic Acid for patients having primary hip or knee arthroplasty. Clinical orthopaedics and related research. 2010 Jul ;468(7):1905-11.
  10. Rajesparan K., Biant L.C., Ahmad M., Field R.E. The effect of an intravenous bolus of tranexamic acid on blood loss in total hip replacement. The Journal of bone and joint surgery. British volume. 2009 Jun ;91(6):776-83.
  11. Lozano M., Basora M., Peidro L., Merino I., Segur J.M., Pereira A., et al. Effectiveness and safety of tranexamic acid administration during total knee arthroplasty. Vox sanguinis. 2008 Jul ;95(1):39-44.
  12. Johansson T., Pettersson L-G., Lisander B. Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients. Acta orthopaedica. 2005 Jun ;76(3):314-9.
  13. Niskanen R.O., Korkala O.L. Tranexamic acid reduces blood loss in cemented hip arthroplasty: a randomized, double-blind study of 39 patients with osteoarthritis. Acta orthopaedica. 2005 Dec ;76(6):829-32.
  14. Orpen N.M., Little C., Walker G., Crawfurd E.J.P. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. The Knee. 2006 Mar ;13(2):106-10.
  15. Camarasa M.A., Ollé G., Serra-Prat M., Martín A., Sánchez M., Ricós P., et al. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. British journal of anaesthesia. 2006 May ;96(5):576-82.
  16. Molloy D.O., Archbold H.A.P., Ogonda L., McConway J., Wilson R.K., Beverland D.E. Comparison of topical fibrin spray and tranexamic acid on blood loss after total knee replacement: a prospective, randomised controlled trial. The Journal of bone and joint surgery. British volume. 2007 Mar ;89(3):306-9.
  17. Claeys M.A., Vermeersch N., Haentjens P. Reduction of blood loss with tranexamic acid in primary total hip replacement surgery. Acta chirurgica Belgica. 107(4):397-401.
  18. Alvarez J.C., Santiveri F.X., Ramos I., Vela E., Puig L., Escolano F. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion. 2008 Mar ;48(3):519-25.
  19. Gill J.B., Rosenstein A. The use of antifibrinolytic agents in total hip arthroplasty: a meta-analysis. The Journal of arthroplasty. 2006 Sep ;21(6):869-73.


Reprinted with permission from the Summer 2011 issue of COA Bulletin

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