CORR Insights®: No Difference in Blood Loss and Risk of Transfusion Between Patients Treated with One or Two Doses of Intravenous Tranexamic Acid After Simultaneous Bilateral TKA

Where Are We Now?

Tranexamic acid (TXA) is effective in reducing postoperative blood loss and minimizing transfusion [5] both in unilateral and single-stage bilateral primary TKA [2, 4]. Prior to the widespread use of TXA in TKA, at least one-third of patients receiving TKA received a blood transfusion after the operation [3], and more than 50% of patients receiving single-stage bilateral TKA received a transfusion [12]. The incidence of transfusion after TKA is reduced to less than 24% in patients having perioperative TXA [2].

In a recent network meta-analysis of 67 randomized controlled trials studying the use of TXA in primary TKA, the authors found that TXA in unilateral TKA was similarly effective regardless of the route of administration (topical, intravenous, oral) or the dosing regimen (low dose versus high dose; single-dose regimen vs. multiple-dose regimen) [3]. The time of intravenous TXA administration as it relates to the time of surgery was the only variable that affected the outcome, with administration prior to incision being favored over administering it after the procedure began when single-dose TXA was used [3].

Randomized controlled trials have examined the efficacy of different protocols of administration of TXA for single-stage bilateral TKA [1, 7, 10], but it remains uncertain whether one approach to administering TXA is superior to others, or whether there is an efficacy difference among different TXA dosing regimens.

Enter Wilde and colleagues [11], who found that when compared with a two-dose regimen, a single-dose regimen of intravenous TXA adequately prevented excessive blood loss and minimized the usage of blood transfusions in single-stage sequential bilateral TKA.

Based on these findings, surgeons can give the lowest effective dose of TXA during single-stage sequential bilateral TKA. This approach reduces the cost and minimizes any possible complications associated with the use of TXA.

Where Do We Need To Go?

Two recent meta-analyses examining the use of TXA in primary TKA found that the incidence of major medical complications, including thromboembolic events, myocardial infarction, or stroke, were comparable between the TXA group and a placebo group [2, 4]. However, since the incidence of thromboembolic events and other major medical complications in these studies was extremely low, there was a concern regarding whether these studies were adequately powered to demonstrate the safety of TXA [5]. In the absence of high-quality evidence on the safety profile of TXA, administering the smallest effective dose will be the best approach to reduce the risk of medical complications.

Single-stage bilateral TKA is associated with longer surgical time and more intraoperative bleeding compared to unilateral TKA [12]. TXA helps control bleeding by inhibiting fibrinolysis [9]. Repeated doses of TXA should be given at 4-hour intervals to maintain the plasma therapeutic level, since the half-life of TXA is known to be short [8]. A multiple-dosing regimen may be beneficial if the operation is longer than 4 hours. Wilde and colleagues [11] showed that a single-dose regimen of intravenous TXA was adequate to reduce the usage of blood transfusions in single-stage bilateral TKA. However, it is not known whether similar results can be reproduced in other centers, especially those with a lower TKA practice volume. I believe that the length of operation is an important variable affecting the applicability of a single-dose TXA regimen in single-stage bilateral TKA, but additional studies are needed to confirm this.

Revision TKA and difficult primary TKA (those with severe preoperative deformity, marked stiffness, or bone loss) are more likely to be associated with greater blood loss and a higher risk of transfusion. Similar to single-stage bilateral TKA, these are the procedures that will benefit more from the use of TXA. However, a majority of the available published randomized controlled trials focus on the use of TXA in primary TKA [1-5, 7, 10]. Still, it is likely that the successful results of TXA in a primary procedure can be extrapolated to difficult primary TKA (those that require extensive soft tissue release and major bone defect reconstruction) and revision TKA.

How Do We Get There?

The most practical way to study the safety profile of TXA in TKA is by examining national registry data. It allows data from a large population to be assessed, solving the issues of inadequate sample size. This is possibly the only way to examine incidence of uncommon complications or side effects of a drug or procedure [6].

Determining the efficacy of a single-dose regimen of TXA in single-stage bilateral TKA in low-volume centers can be done by retrospectively studying the registry data. If a major difference in the amount of bleeding and transfusion is found between low-volume and high-volume surgeons, we could then repeat the study on the scale of a multicenter trial involving surgeons who treat different volumes of patients who have undergone TKA. Such a study could help us determine the effect of the length of operation time on the efficacy of TXA. Having such data could help surgeons develop a more refined guideline in how we should use TXA in single-stage bilateral TKA.