Comparison of Topical and Intravenous Tranexamic Acid for Total Knee Replacement

Abstract

Background: Tranexamic acid (TXA) is an antifibrinolytic drug. Topical administration of TXA during total knee arthroplasty (TKA) is favored for certain patients because of concerns about thrombotic complications, despite a lack of supporting literature. We compared local and systemic levels of thrombogenic markers, interleukin (IL)-6, and TXA between patients who received intravenous (IV) TXA and those who received topical TXA. Methods: Seventy-six patients scheduled for TKA were enrolled in this randomized double-blinded study. The IV group received 1.0 g of IV TXA before tourniquet inflation and again 3 hours later; a topical placebo was administered 5 minutes before final tourniquet release. The topical group received an IV placebo before tourniquet inflation and again 3 hours later; 3.0 g of TXA was administered topically 5 minutes before final tourniquet release. Peripheral and wound blood samples were collected to measure levels of plasmin-anti-plasmin (PAP, a measure of fibrinolysis), prothrombin fragment 1.2 (PF1.2, a marker of thrombin generation), IL-6, and TXA. Results: At 1 hour after tourniquet release, systemic PAP levels were comparable between the IV group (after a single dose of IV TXA) and the topical group. At 4 hours after tourniquet release, the IV group had lower systemic PAP levels than the topical group (mean and standard deviation, 1,117.8 ± 478.9 µg/L versus 1,280.7 ± 646.5 µg/L; p = 0.049), indicative of higher antifibrinolytic activity after the second dose. There was no difference in PF1.2 levels between groups, indicating that there was no increase in thrombin generation. The IV group had higher TXA levels at all time points (p < 0.001). Four hours after tourniquet release, wound blood IL-6 and TXA levels were higher than systemic levels in both groups (p < 0.001). Therapeutic systemic TXA levels (mean, 7.2 ± 7.4 mg/L) were noted in the topical group. Calculated blood loss and the length of the hospital stay were lower in the IV group (p = 0.026 and p = 0.025). Conclusions: Given that therapeutic levels were reached with topical TXA and the lack of a major difference in the mechanism of action, coagulation, and fibrinolytic profile between topical TXA and a single dose of IV TXA, it may be a simpler protocol for institutions to adopt the use of a single dose of IV TXA when safety is a concern. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Intra-articular vs. intravenous administration: a meta-analysis of tranexamic acid in primary total knee arthroplasty

“…The random-effects model ( P < 0.001, I 2 = 91%) was used for analysis, and there was no significant difference between the IV and IA groups (MD = − 0.34, 95% CI = − 0.70 to 0.02, P = 0.07). Regarding the high heterogeneity, a sensitivity analysis was performed and two studies were excluded [ 14 , 48 ], then we got a lower heterogeneity result ( P = 0.14, I 2 = 36%) by analyzing the rest of 8 studies including 839 patients with a fixed-effects model. No significant difference was shown between the IV and IA groups (MD = − 0.01, 95% CI = − 0.11 to 0.13, P = 0.86).…”

Role of Tranexamic Acid in Arthroscopic Osteocapsular Release of the Elbow for Degenerative Arthritis

“…The efficacy and safety of IV versus topical TXA are still debated; however, most studies have shown that both routes are equally effective in reducing the level of bleeding. 5 , 7 , 14 Jules-Elysee et al 14 compared topical and IV TXA for total knee arthroplasty and demonstrated that IV TXA resulted in higher wound concentrations, suggesting that the wound was the major site of action despite the mode of administration; lower systemic TXA levels were observed in the topical group; but both were within therapeutic range. In terms of safety, there is now emerging evidence that IV TXA is not associated with increased complications in patients with a history of thrombotic events and does not increase the risk of perioperative seizures.…”

Efficacy and Systemic Absorption of Peri-articular Versus Intra-articular Administration of Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

“…A randomized controlled trial study by Jules-Elysee et al. [ 34 ] compared serum TXA levels between patients who received intravenous TXA (2 g) and IA-TXA (3 g). The intravenous group received 1 g before tourniquet inflation and 1 g at 3 hours later.…”