Total knee arthroplasty (TKA) is associated with postoperative blood loss requiring blood transfusion in up to a third of patients.1-2  The reported blood loss ranges from 1,450 to 1,790 mL, leading to anaemia in many patients.3-4 Postoperative anaemia in older patients has increased significance due to their reduced haematopoietic reserve. Adverse effects of anaemia include the need for transfusion, longer hospital stays, and associated increased costs.

With changing demographics worldwide, the demand for TKA is expected to increase exponentially.  Topical application of tranexamic acid (TXA) provides a novel approach for decreasing blood loss after TKA. It is cost-effective compared with preoperative erythropoietin and autologous blood donation.6-7

Several experimental studies have demonstrated the molecular basis for the function of TXA, which acts by binding to the lysine-binding sites of plasmin and plasminogen. Saturation of these sites displaces plasminogen from the fibrin surface, thus inhibiting fibrinolysis.  The use of TXA has been shown to be effective in reducing postoperative blood loss in cardiac, dental,10 and spinal surgery.11

  • De Bonis et al compared the postoperative bleeding following topical application of TXA versus a placebo for cardiac bypass surgery. They demonstrated a 36% reduction in bleeding at 3 hours and a 25% reduction at 24 hours.12
  • Oral TXA mouthwash is routinely used following dental surgery to reduce postoperative bleeding. Tsutsumimoto et al studied the efficacy of TXA in reducing perioperative blood loss following cervical laminoplasty.  In the TXA group, postoperative blood loss during the first 16 hours was reduced by 37% compared with the control group. The total blood loss in the TXA group was significantly lower than in the control group.13
  • Lin et al reported a significant reduction in blood loss and need for transfusion in patients undergoing minimally invasive TKA.14  Dhillon et al showed TXA to be effective in reducing postoperative blood loss and transfusion requirements in patients undergoing bilateral TKA.15

Systemic administration of TXA carries the risk of thromboembolic events. Given intravenously, TXA is widely distributed throughout the extra and intracellular compartments.16   It has been shown to diffuse into the synovial membrane and synovial fluid and achieve the same concentration in the joint fluid as the serum. The half-life within the joint fluid is 3 hours.17  The mode of excretion is by glomerular filtration, with 90% excretion at 24 hours.16  Topical application of TXA is a simple and inexpensive procedure with minimal systemic absorption. It is a cheaper alternative to the fibrin sealants currently in use,18  which carry a risk of infective transmission as they are derived from human plasma.19

We performed a randomised controlled trial of 99 patients who underwent a TKA, comparing the local effects of TXA in reducing postoperative blood loss and reducing the need for postoperative transfusion. Three subgroups were formed, with one group receiving a saline placebo, one group receiving 1.5g TXA, and the third subgroup receiving 3g of TXA. Intra-operatively, at the end of the implantation of the cemented components, study solution was applied to the joint surfaces for 5 minutes. Postoperatively, patients were followed-up for blood loss and need for transfusion. All patients received thromboprophylaxis, and postoperative Doppler study was performed to rule out thromboembolic events.

Our results showed that the topical application of TXA reduced the postoperative blood loss by 20-25% (300-400 mLs) compared with the placebo group. We found no difference in the rates of transfusion between the 1.5-g and the placebo subgroups. None of the patients in the 3-g TXA group required transfusion. Two patients (one in the placebo group and one in 1.5-g group) had symptomatic pulmonary emboli confirmed on spiral computed tomography. Both had negative Doppler studies and were discharged with warfarin for 3 months. Postoperative function and range of movement in the knee were not affected by topical application of TXA in our study.20

In conclusion, topical application of TXA has been shown to reduce blood loss by up to 25%, resulting in 17% higher postoperative haemoglobin values. Further studies are needed to ensure that this simple and cost-effective tool is safe for routine use with regards to thromboembolic complications.

References

  1. Goodnough L.T., Verbrugge D., Marcus R.E. The relationship between haematocrit, blood lost and blood transfused in total knee replacement. Implications for post operative blood salvage and reinfusion. Am J Knee Surg. 1995;8:83-7
  2. Bierbaum B.E., Calaghan J.J., Galante J.O., Rubash H.E., Tooms R.E., Welch R.B. An analysis of blood management in patients having total hip or knee arthroplasty. J Bone Joint Surg Am. 1999;81:2-10
  3. Kalairajah Y., Simpson D., Cossey A.J., Verrall G.M., Spriggins A.J. Blood loss after Total knee replacement: effect of computer assisted surgery. J Bone Joint Surg Br. 2005;87:1480-2
  4. Freedman J., Luke K., Monga N., Lincoln N., Koen R., Escobar M., Chiavetta J_. A provincial program of blood conservation:the Ontario transfusion coordinators(ONTraC)._ Transfus Apher Sci. 2005;33:343-9
  5. Lanes S.F., Lanza L.L., Radensky P.W., Yood R.A., Meenan R.F., Walker A.M., Dreyer N.A., Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis in a managed care setting: the importance of drug and surgery costs. Arthritis Rheum. 1997;40:1475-81
  6. Birkmeyer J.D., Goodnough L.T., AuBuchon J.P., Noordsij P.G., Littenberg B. The cost effectiveness of preoperative autologous blood donation for total hip and knee replacement. Transfusion. 1993;33:544-51
  7. Alvarez J.C., Santiveri F.X., Ramos I., Vela E., Puig L., Escolano F. TXA reduces blood transfusion in total knee arthroplasty even when blood conservation program is applied. Transfusion. 2008;48:519-25
  8. Longstaff C. Studies on the mechanisms of action of aprotinin and TXA as plasmin inhibitors and antifibrinolytic agents. Blood Coagul Fibrinolysis 1994:537-542.
  9. Fawzy H., Elmistekawy E., Bonneau D., latter D., Erret L. Can local application of TXA reduce post-coronary bypass surgery blood loss? A randomised control trial. J Cardiothorasic Surg. 2009;4:25
  10. Sindet-Pederson S., Ramström G., Bernvil S., Blombäck M. Hemostatic effect of TXA mouthwash in anticoagulant treated patients undergoing oral surgery. N Engl J Med. 1989;320:840-3
  11. Krohn C.D., Sørenson R, Lange J.E., Riise R., Bjørnsen S., Brosstad F. TXA given into wound reduces post operative blood loss by half in major orthopaedic surgery. Eur J Surg Suppl. 2003;588:57-61
  12. De Bonis M., Cavaliere F., Alessandrini F., Lapenna E., Santarelli F., Moscato U., Schiavello R., Possati G.F. Topical use of TXA in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study J Thorac Cardiovasc Surg 2000;119:575-580.
  13. Tsutsumimoto T., Shimogata M., Ohta H., Yui M., Yoda I., Misawa H., Tranaxemic acid reduces perioperative blood loss in cervical  laminoplasty: A prospective randomised study. Spine, 2011 Feb 1(Epub ahead of print).
  14. Lin P.C., Hsu C.H., Chen W.S., Wang J.W_. Does TXA save blood in minimally invasive total knee arthroplasty?_ Clin Orthop Relat Res 2011. Feb 1. ( Epub ahead of print)
  15. Dhillon M.S., Bali K., Prabhakar S., Tranexamic Acid for control of blood loss in bilateral total knee replacement in a single stage. Indian J Orthop 2011 Mar;45(2):148-52
  16. Nilsson I.M. Clinical pharmacology of aminocaproic acid and TXAs. J Clin Pathol Suppl ( R Coll Pathol). 1980;14:41-7
  17. Ahlberg A., Eriksson O., Kjellman H. Diffusion of TXA to the joint. Acta Orthop Scand. 1976;47:486-8
  18. Wang G.J., Hungerford D.S., Savory C.G., Rosenberg A.G., Mont M.A., Burks S.G., Mayers S.l., Spotnitz W.D. Use of fibrin sealent to reduce bloody drainage and haemoglobin lossafter total knee arthroplasty: a brief note on randomised prospective trial. J Bone Joint Surg Am. 2001;83:1503-5
  19. Radosevich M., Goubran H.I., Burnouf T. Fibrin sealant: scientific rationale, production methods, properties and current clinical use. Vox Sans. 1997;72:133-43
  20. Wong J., Abrishami A., El Beheiry H., Mahomed N.N., Davey J.R., Gandhi R., Syed K.A., Hassan S.M.O., De Silva S., Chung F. Topical application of TXA reduced postoperative blood loss in total knee arthroplasty. J Bone Joint Surg Am. 2010;92:2503-13



Reprinted with permission from the Summer 2011 issue of COA Bulletin