Topical and Intra-articular Tranexamic Acid in Total Knee Arthroplasty

Prasad Antapur, MRCS, FRCS(Tr & Orth)
Clinical Arthroplasty Fellow,
Southampton University Hospitals NHS Trust,
Southampton, United Kingdom

Rajiv Gandhi, M.D., MSc, FRCSC
Assistant Professor, Department of Orthopaedics,
Toronto Western Hospital,
Toronto, ON

Nizar N. Mahomed, M.D., ScD, FRCSC
Smith & Nephew Chair in Orthopaedic Surgery, Professor of Surgery,
University of Toronto, Department of Orthopaedics,
Toronto Western Hospital,

Total knee arthroplasty (TKA) is associated with postoperative blood loss requiring blood transfusion in up to a third of patients1-2. The reported blood loss ranges from 1450 to 1790 ml leading to anaemia in many patients3-4. Postoperative anaemia in the elderly patient group has increased significance due to the reduced haematopoietic reserve. Adverse effects of anaemia include need for transfusion, longer hospital stay and associated increased costs. With changing demographics worldwide, the demand for TKA is expected to increase exponentially5. Topical application of tranexamic acid (TXA) provides a novel approach for decreasing blood loss after TKA. It is cost-effective compared to preoperative erythropoietin and autologous blood donation6-7.


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 fibrinolysis8. The use of TXA has been shown to be effective in reducing postoperative blood loss in cardiac9, dental10 and spinal surgery11. 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 three hours and a 25% reduction at 24 hours12. Oral TXA mouthwash is routinely used following dental surgery to reduce the 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% as compared to the control group. The total blood loss in the TXA group was significantly lower than that in the control group13. Lin et al. reported a significant reduction in blood loss and need for transfusion in patients undergoing minimally invasive TKA14. Dhillon et al. showed TXA to be effective in reducing postoperative blood loss and transfusion requirements in patients undergoing bilateral TKA's15.

Systemic administration carries the risk of thromboembolic events. Given intravenously, TXA is widely distributed throughout the extra and intracellular compartments16. 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 three hours17. The mode of excretion is by glomerular filtration with 90% excretion at 24 hours16. Topical application of TXA is a simple and inexpensive procedure with minimal systemic absorption. It is a cheaper alternative compared to fibrin sealants currently in use18, which carry a risk of infective transmission as they are derived from human plasma19.

We performed a randomized 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 five 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% (300-400mls) compared to the placebo group. We found no difference in the rates of transfusion between 1.5g and placebo subgroups. None of the patients in the 3g TXA group required transfusion. Two patients (one in the placebo group and one in 1.5g group) had symptomatic pulmonary emboli confirmed on spiral computed tomography. Both had negative Doppler study and were discharged with warfarin for three months. Postoperative function and range of movement in the knee were not affected by topical application of TXA in our study20.

In conclusion, topical application of tranexamic acid has been shown to reduce blood loss by up to 25% resulting in a 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.



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