Effect of Tranexamic Acid on Blood Loss in Reverse Total Shoulder Arthroplasty

Study Title: Effect of TXA on intra-operative blood loss in reverse total shoulder arthroplasty, a randomized controlled trial I. Purpose, Background and Rationale A. Aim and Hypotheses 1. Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent that has been well studied and routinely used for hip and knee arthroplasty. In hip and knee arthroplasty, the use of tranexamic acid decreases blood loss and the need for transfusion without increasing the risk of thromboembolic events. Due to the increased use of reverse total shoulder arthroplasty in the treatment of shoulder pathology, there has been interest in making the procedure safer for patients. TXA is a promising drug which could be useful to surgeons as they seek to achieve this goal, however, it has not been extensively studied in this setting. The purpose of this prospective randomized, controlled study is to determine the effectiveness and safety of using tranexamic acid to decrease blood loss in reverse total shoulder arthroplasty. 2. Investigators hypothesize that patients who receive an intra-operative administration of tranexamic acid (TXA), as compared to control patients who do not receive TXA, will:

1. Have decreased intra-operative blood loss as estimated by the operating surgeon
2. Have a smaller drop in hemoglobin as measured with a complete blood count performed on post-op day one
3. Have less post-operative drain output
4. Have no increase in the rate of adverse events including venous thromboembolic events or infection. B. Background and Significance Tranexamic acid (TXA) is a synthetic lysine analog which competitively inhibits the activation of plasminogen to plasmin, preventing the breakdown of the fibrin matrix. This effectively stabilizes clot formation and has been shown to decrease blood loss in multiple settings. In total hip and total knee arthroplasty, the use of TXA has been shown to decrease blood loss and the need for blood transfusion in the perioperative period.

Despite its clot-stabilizing effect, TXA has not been shown to increase the risk of thromboembolic events (Duncan et al.,2015; Yang et al., 2013). Intravenous tranexamic acid is FDA approved for use in hemophilia and to reduce bleeding complications for The use of TXA in total shoulder arthroplasty has been less well studied. The rate of blood transfusion in these procedures, although lower than hip and knee arthroplasty, is reported between 4 and 43%. A retrospective study by Hardy et al. in 2013 showed an overall transfusion rate of 7.4%, with intra-operative estimated blood loss being an independent risk factor for transfusion. The risks associated with blood transfusion have been decreased with modern screening methods, however, there are multiple studies specific to hip and knee arthroplasty showing an association with adverse events such as infection, venous thromboembolic events, and even mortality. In addition, Grier et al.

used the Medicare Standard Analytic files database to study over 7500 patients who received a blood transfusion after anatomic or reverse total shoulder arthroplasty and compared them to age- and gender-matched controls. They found a statistically increased rate of myocardial infarction, pneumonia, sepsis, and cerebrovascular accident in the transfusion group. Methods to reduce blood loss and, therefore, the rate of transfusion are clearly invaluable in improving patient outcomes for shoulder arthroplasty. A few studies over the last two years have looked at the role of tranexamic acid in total shoulder arthroplasty. Two retrospective review studies have shown that TXA can be effective in decreasing blood loss and length of hospital stay in patients undergoing reverse or anatomic total shoulder arthroplasty (Abilgaard et al., 2016; Friedman et al., 2018). A randomized control trial including 54 patients undergoing reverse or anatomic total shoulder arthroplasty demonstrated decrease blood loss, patient-reported pain, and hematoma formation (Pauzenberger et al., 2017). One study specific to reverse total shoulder arthroplasty showed a decrease in blood loss (1124 ml in the control group, 411 in the TXA group). In this study, 7 transfusions were reported in the control group compared to 3 in the TXA group. The patients in this study received prophylactic heparin during their hospital stay. A meta-analysis of 5 studies, including those described above, included a total of 629 patients and showed that patients receiving TXA had decreased blood loss. There was no increase in adverse events in the TXA group patients. These studies indicate that tranexamic acid may be effective in decreasing the amount of blood loss during reverse total shoulder arthroplasty. However, these studies are heterogeneous in that several of them include patients undergoing either reverse or anatomic total shoulder arthroplasty, which are inherently different procedures regarding the implants used and the specific risks involved. Please see the literature cited section for full citations. C. Rationale This study aims to add to the currently small body of literature regarding the role of tranexamic acid in reverse total shoulder arthroplasty. Several elements of our study are unique. First, investigators will include only patient's undergoing reverse total shoulder arthroplasty. In addition, patients will not receive chemoprophylaxis against deep venous thrombosis. This is the standard of care at our institution, where it has been noted less blood loss and a decreased transfusion rate as compared to the published studies.

II. Research Plan and Design