The Role of Topically Administered Tranexamic Acid in Arthroplasty.

The use of intravenously administered tranexamic acid (TXA) has been a well-known and established method of reducing perioperative blood loss and the need for allogeneic blood transfusion in the field of orthopedics. In addition to reducing blood loss, numerous studies have reported a lower incidence of early postoperative infections when using TXA. This observation was attributed to reduced blood transfusions and their immunomodulatory effects, beneficial effects on wound healing, and anti-inflammatory propertied of TXA. The efficacy and safety of intravenous TXA in arthroplasty have been confirmed by numerous meta-analyzes and clinical studies, while on the other hand there is little information available on the effects of topical TXA, which has been shown to be similarly effective in providing hemostasis. Due to the presumed lower risk of thromboembolic and other systemic side effects, intra-articular (i.a.) application of TXA is increasingly used, especially in arthroplasty. However, this mode of application remains controversial due to the confirmed cytotoxic effect of TXA on periarticular tissues, which increases with concentration of TXA and time of exposure. At the same time, actual local concentrations of TXA after i.a. application have not yet been researched; therefore, we do not know how long after i.a. application the concentrations in the periarticular hematoma are above the presumed cytotoxic threshold. There are also no known data on the possible cytotoxic effects of TXA on bacteria and its contribution on the observed lower incidence of early postoperative infections. In the case of topical application, where higher local concentrations are achieved, this potential effect is expected to be even greater than with IV application. In the proposed research project, designed from four working segments, we will measure the actual in vivo concentrations of TXA in the periarticular hematoma after standard i.a. application and explain the influence of topical TXA on the local immune response by measuring the concentrations of inflammatory cytokines in the periarticular hematoma. An in vitro experiment will be executed to evaluate the cytotoxic effect of TXA on the most common bacterial pathogens associated with early postoperative infections and elucidate its indirect effect on the incidence of early postoperative infections after arthroplasty. The effect of intra-articular TXA on the occurrence of surgical wound infections and early periprosthetic joint infections, together with the effect on perioperative blood loss and the need for blood transfusion, will additionally be examined by a retrospective cohort study. The research project will be carried out in cooperation of the Valdoltra Orthopedic Hospital Research group and the Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana. Majority of activities composing the project will be carried out at the Valdoltra Orthopedic Hospital, while the analysis of TXA and cytokine concentrations in the hematoma samples will be performed at the Institute of Biochemistry and Molecular Genetics.