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    Is There an Optimal Dosing Regimen for TXA in Revision Total Knee Arthroplasty?

    Tranexamic acid (TXA) is commonly used in topical, oral, and intravenous (IV) forms to safely and effectively reduce blood loss and transfusions in patients undergoing primary total knee arthroplasty (TKA). [1-7] Less is known about the blood-sparing effects of TXA in revision TKA patients, who typically experience more blood loss than primary TKA patients.

    To better understand the use of TXA in revision TKA, surgeons from 6 institutions in the US – Mayo Clinic, NYU Langone Health, Hospital for Special Surgery, University of California San Francisco, and Rush University Medical Center – participated in a randomized trial designed to evaluate 4 dosing regimens in patients undergoing septic and aseptic revision TKA:

    • 1 gram of IV TXA before the first incision
    • 1 gram of IV TXA before the first incision and 1 gram of IV TXA at wound closure
    • 1 gram of IV TXA before the first incision and 1 gram of topical TXA intraoperatively
    • 3 1950-mg doses of oral TXA: 2 hours preoperatively, 6 hours postoperatively, and the morning of POD1

    Each treatment group included a mix of patients undergoing different types of revisions:

    • Femoral component exchange
    • Tibial component exchange
    • Both component exchange
    • Explant of both components and placement of antibiotic cement spacer
    • Second-stage re-implantation procedure
    • Conversion of unicompartmental knee arthroplasty to TKA

    The researchers found no significant differences among the treatment regimens for:

    • Reduction in hemoglobin (the primary outcome measure): 2.88 g/dL for oral TXA, 2.79 g/dL for single-dose IV TXA, 2.59 g/dL for combined IV/topical TXA, and 2.58 g/dL for double-dose IV TXA (P=0.48).
    • Calculated blood loss: 1321 mL for oral TXA, 1466 mL for single-dose IV TXA, 1290 mL for combined IV/topical TXA, and 1229 mL for double-dose IV TXA (P=0.63)
    • Transfusion rates: 4.1% for oral TXA, 6.0% for single-dose IV TXA, 2.1% for combined IV/topical TXA, and 2.1% for double-dose IV TXA (P=0.78)

    “We expected one of the dosing regimens to be better than the rest, but our data showed that there were no real clinically relevant differences, at least amongst the regimens we chose to study,” said senior study author Craig J. Della Valle, MD, from Rush University Medical Center.

    Lead author Yale Fillingham, MD, formerly from Rush University Medical Center and now at Dartmouth-Hitchcock Medical Center, agreed, noting that, “Because revision procedures are associated with a higher risk of blood loss and transfusion, we had expected to see a difference between the groups,” he said.

    With no dosing regimen found to be superior to another, “you can use the same dosing regimen (for revisions) that you use now for primary arthroplasty,” Dr. Della Valle said.

    Cost may end up being the driver of the regimen used at some institutions: In this study, a dose of oral TXA cost $14, compared with $47 to $108 for a dose of topical or IV TXA.

    “We suggest using the lowest dose that is most economical or easiest to give,” Dr. Della Valle said. “At our institution we have been using oral TXA as it is inexpensive and easily given before the patient gets to the operating room. The important thing is to use something!”

    Findings of the study were presented at the 2019 Annual Meeting of the American Academy of Orthopaedic Surgeons.

    Source

    Fillingham Y, Darrith B, Abdel MP, Malkani AL, Schwarzkopf R, Padgett DE, Sershon RA, Bini SA, Della Valle CJ. A Multi-Center Randomized Clinical Trial of Tranexamic Acid in Revision Total Knee Arthroplasty: Does the Dosage Regimen Matter? (Paper 097). Presented at the 2019 Annual Meeting of the American Academy of Orthopaedic Surgeons, March 12-16, Las Vegas, Nevada.

    References

    1. Tang Y, Wen Y, Li W, Li H, Yang Y, Liu Y. The efficacy and safety of multiple doses of oral tranexamic acid on blood loss, inflammatory and fibrinolysis response following total knee arthroplasty: A randomized controlled trial. Int J Surg. 2019 Mar 20;65:45-51. doi: 10.1016/j.ijsu.2019.03.011. [Epub ahead of print]
    2. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. Tranexamic acid in total joint arthroplasty: the endorsed clinical practice guides of the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. Reg Anesth Pain Med. 2019 Jan;44(1):7-11. doi: 10.1136/rapm-2018-000024.
    3. Yaghmour KM, Atkinson S, Chisari E, McDonnell S, Khan W. Effectiveness and safety of tranexamic acid in total joint arthroplasty. J Perioper Pract. 2019 Jan 16:1750458919825812. doi: 10.1177/1750458919825812. [Epub ahead of print].
    4. Laoruengthana A, Rattanaprichavej P, Rasamimongkol S, Galassi M, Weerakul S, Pongpirul K. Intra-articular tranexamic acid mitigates blood loss and morphine use after total knee arthroplasty. A randomized controlled trial. J Arthroplasty. 2019 Jan 23. pii: S0883-5403(19)30075-0. doi: 10.1016/j.arth.2019.01.030. [Epub ahead of print]
    5. Sun Q, Li J, Chen J, Zheng C, Liu C, Jia Y. Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials. BMJ Open. 2019 Jan 28;9(1):e024350. doi: 10.1136/bmjopen-2018-024350.
    6. Lum ZC, Manoukian MAC, Pacheco CS, Nedopil A, Giordani M, Meehan JP. Intravenous tranexamic acid versus topical aminocaproic acid: which method has the least blood loss and transfusion rates? J Am Acad Orthop Surg Glob Res Rev. 2018 Nov 7;2(11):e072. doi: 10.5435/JAAOSGlobal-D-18-00072. eCollection 2018 Nov.
    7. Melvin JS, Stryker LS, Sierra RJ. Tranexamic acid in hip and knee arthroplasty. J Am Acad Orthop Surg. 2015 Dec;23(12):732-40. doi: 10.5435/JAAOS-D-14-00223. Epub 2015 Oct 22.