Making Tranexamic Acid the Standard of Care in Hip and Knee Arthroplasty

Commentary A theoretical drawback of the use of antifibrinolytics in total joint arthroplasty (TJA), and tranexamic acid (TXA) specifically, has been the concern regarding an increase in venous thromboembolism (VTE). This has probably been the single-most important factor affecting the slow uptake and usage of this drug, despite the large amount of published literature demonstrating efficacy and safety going back to the late 1990s1,2. A number of early studies were published mainly in the European anesthesia literature, and as a result, received little readership among North American orthopaedic surgeons. Over the next 10 years, numerous attempts to limit postoperative transfusions following TJA, such as preoperative administration of erythropoietin, preoperative autologous donation for postoperative transfusion, intraoperative blood salvage, and postoperative reinfusion, failed to result in a substantial decrease in the transfusion rate. In the mid 2000s, transfusion rates were still as high as 46% to 56% following TJA3,4. Because antifibrinolytics are inexpensive generic drugs, there was no “Big Pharma” push to promote TXA usage. Gradually, in the mid-to-late 2000s, various centers around the United States and Canada began using TXA and publishing their results, which validated those published 10 years earlier. However, the uptake has been slow at best, as a result of a number of perceived issues, the main one being the increased occurrence of VTE. Another concern exists regarding the use of TXA in patients with a history of cardiovascular disease. Numerous individual studies, meta-analyses, and systematic reviews, such as that by Sukeik et al., have shown no increase in VTE or cardiovascular events5. Surgeons, however, still remain skeptical and concerned because of the limited numbers of patients in the published studies and the low incidence of the perceived complications. A common misconception regarding usage is that surgeons cannot use the drug off-label for fear of medicolegal repercussions. Although it is true that the only indication for TXA that has been approved by the U.S. Food and Drug Administration (FDA) is for limiting blood loss during tooth extraction in patients with hemophilia, the concern is no longer justified, as there are sufficient published data, both in cardiovascular and orthopaedic surgery, substantiating TXA use on the basis of its benefits to the patient and the health-care system. The large database study by Hallstrom et al., which involved almost 35,000 patients, may finally put these concerns to rest and allow for antifibrinolytics to become the standard of care in TJA. Once again, no increase in the risk of VTE or in cardiovascular events was demonstrated, while the benefits remained substantial. The authors demonstrated that previously published clinical trial results are applicable to a broader, unselected real-world population. While this study did not address the dosing issue or route of administration, there are numerous protocols of varying dosing strengths and schedules that have been published; the optimal protocol still remains to be determined. In addition, there is a growing body of literature demonstrating the efficacy and safety of topical administration of TXA6. While this appears to be similar to intravenous TXA administration, additional studies are needed to determine which method may be best in various situations, or if a combination may be better. Studies investigating oral TXA as a possible alternative to either of these administration routes are also ongoing. Additional studies are needed to determine if substantial widespread benefits exist for the use of TXA in all TJA patients or if it should be used only in certain select patients who would benefit most. While most studies to date have investigated the use of TXA in primary unilateral TJA, there is a growing body of literature to show benefit in other situations, such as bilateral TJA and revision TJA, clinical situations in which the benefits and cost-savings may be even greater. This article helps to advance the care of our patients and supports the use of antifibrinolytics as a standard of care in TJA.

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