Is TXA Administration Safe in High-Risk TJA Patients?

    The antifibrinolytic agent tranexamic acid (TXA) is generally accepted as a means of reducing intraoperative blood loss – and, thus, avoiding postoperative transfusions – in total joint arthroplasty patients. [1-6]

    Surgeons may shy away from administering TXA in patients with a history of thromboembolic or cardiovascular events, however, for fear of triggering a life-threatening complication.

    Unfortunately, the literature does not offer guidance in this regard, as clinical trials with TXA generally exclude patients with thromboembolic, cardiovascular, and other serious comorbidities – in other words, the patients who are typically undergoing total joint arthroplasty in the real world.

    A new study from Mount Sinai Hospital and the Icahn School of Medicine at Mount Sinai in New York, published online ahead of print by Anesthesiology, has taken a different approach to evaluating the issue of TXA use in high-risk total joint arthroplasty patients. Instead of reviewing data from past clinical trials – which, again, don’t necessarily reflect real world clinical practice – the Mount Sinai researchers used the national Premier Healthcare claims database to determine if there is an association between TXA use and blood transfusions and between TXA use and new onset of complications in patients with pre-existing comorbidities.

    The researchers included in the study more than 765,000 patients who underwent total hip (n=265,158) or total knee arthroplasty (n=499,853) between 2013 and 2016. More than half of these patients (52.9%; n=404,974) received TXA, with the majority (94.3%; n=381,943) receiving the drug intravenously. The most common dose was 2000 mg (51.3%; n=207,907), followed by 1000 mg (29.5%; n=119,275) and 3000 mg (13.5%; n=54,761). The dose was not specified for 23,031 patients (5.7%).

    For the analysis, the researchers divided the high-risk patients into 3 groups:

    • Group I: History of such as venous thromboembolism (VTE), myocardial infarction (MI), seizures, ischemic stroke/transient ischemic attack (TIA) (n=27,890)
    • Group II: History of renal disease (n=44,608)
    • Group III: History of atrial fibrillation (n=45,952)

    Tranexamic acid use in high-risk patients was associated with lower blood transfusion rates and lower rates of complications such as VTE, MI, seizures, and strokes/TIAs when compared with high-risk patients who did not receive TXA. This was true across the 3 groups. In addition, TXA use was associated with a shorter length of hospital stay and lower cost of hospitalization. The TXA dose did not affect the complication rate.

    “This is an important clinical conundrum that keeps on coming up as we are aware of the effectiveness of tranexamic acid, but there is not that much data out there on the safety of using tranexamic acid in high-risk patients,” said Calin S. Moucha, MD, Chief of Adult Reconstruction & Joint Replacement Surgery at Mount Sinai Hospital, and Associate Professor of Orthopedics at the Icahn School of Medicine at Mount Sinai.

    “Our results will help anesthesiologists and surgeons in their clinical decision-making on something that is unlikely to be answered by a clinical trial.”

    The findings of this study supplement previous smaller studies that confirm the safety of the drug when used in patients undergoing total joint arthroplasty. However, the researchers asserted the importance of continued studies to track the safety of TXA in patients undergoing total hip and total knee arthroplasty. Future studies, they said, should focus on more detailed parameters on how to reduce the risk of complications in high-risk patients, such as comparing different ways of administering the drug (oral, intravenous, or topical) and dose adjustments.

    “This is by no means the final ‘say’ on this topic, but yet another encouraging sign of the safety of this drug,” said Jashvant Poeran MD, PhD, Director of the Center for Clinical and Outcomes Research, and Associate Professor of Population Health Science & Policy and Orthopedics at the Icahn School of Medicine at Mount Sinai.

    “With an aging population, the demand for such orthopaedic surgeries is going to increase and it is, therefore, important to continue to study ways to improve patient care and outcomes.”


    Poeran J, Chan JJ, Zubizarreta N, Mazumdar M, Galatz LM, Moucha CS. Safety of tranexamic acid in hip and knee arthroplasty in high-risk patients. Anesthesiology. 2021 Apr 15. doi: 10.1097/ALN.0000000000003772. Online ahead of print.


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