Tranexamic acid: When is enough (data) enough?

Abstract

Tranexamic acid (TXA) is a synthetic analog of the amino acid lysine which exerts its effect by binding with the lysine-binding sites on the plasminogen molecule. It reversibly and competitively reduces the affinity of plasminogen binding with fibrin, decreases the activation of plasminogen to plasmin, and reduces the local degradation of fibrin by plasmin. Since its development in the early 1960s, TXA has been proven to be a remarkably effective drug in reducing perioperative blood loss and therefore the requirement for transfusion. 1,2 Nowhere has this been more apparent than in orthopedic surgery, especially in patients undergoing major joint replacement procedures. Until recently, concerns over TXA's theoretical potential to increase postoperative venous thrombotic events (VTE) have unfortunately delayed or even prevented its broader use among arthroplasty patients. Venous thrombotic events remain a concern in arthroplasty patients who are especially vulnerable to thrombotic complications postoperatively.Initial in vitro studies have shown that a concentration of 100 mgÁL -1 was required to produce a 98-100% reduction in fibrinolytic activity. 1 Subsequent clinical experience has shown that an 80% reduction in fibrinolytic activity was sufficient for clinical needs, and this was produced with a TXA concentration of 10 mgÁL -1 . 1 The optimal dose and route of administration to be used in arthroplasty patients remain unclear. In a recent meta-analysis, 46 randomized controlled trials involving 2,925 patients undergoing an orthopedic procedure were identified and included in the analysis. 3 In 21 studies, TXA was given in doses \ 15 mgÁkg -1 , and in 18 studies, TXA was given in doses [ 15 mgÁkg -1 . A single bolus given preoperatively was used in 20 studies, and repeated boluses were given in 26 studies. When all doses and schedules were pooled, TXA was associated with a mean reduction in total blood loss of -408 mL (95% confidence interval [CI], -506 to -311), leading to a halving of the likelihood of allogeneic blood transfusion (relative risk, 0.51; 95% CI, 0.46 to 0.56). Subgroup analysis showed that reductions in transfusion were similar in both single and multiple TXA dosing regimens. In addition, these authors did not observe any statistically significant increases in thromboembolic events. There were similar rates of deep venous thrombosis (DVT) in the TXA and control groups [30 of 1,376 (2.18%) patients and 26 of 1,313 (1.98%) patients, respectively; relative risk, 1.11; 95% confidence interval, 0.69 to 1.79].Despite the plethora of individual studies and meta-analyses, the routine use of TXA in this at-risk patient population has been limited by what some clinicians consider to be an insufficiency of data. This is mainly due to the small sample size of the majority of studies, thus requiring meta-analyses to characterize the safety and harm of therapy. A recent large retrospective cohort study drawn from administrative health data may have put some of these concerns to rest. 4 In this study of 872,4...

Perioperative Tranexamic Acid Treatment and Risk of Cardiovascular Events or Death After Total Hip Arthroplasty

“…Given the pharmacological action of TXA, there are concerns about the routine use of TXA in THA and the risk of inducing a hypercoagulatory state with an increased risk of venous thromboembolism (either deep venous thrombosis or pulmonary embolism) and possibly other cardiovascular outcomes such as myocardial infarction or ischemic stroke 10,11 . However, we are not aware of any study that has shown perioperative TXA to be associated with an increased risk of thromboembolic events 12,13 .…”

A rationale for universal tranexamic acid in major joint arthroplasty: overall efficacy and impact of risk factors for transfusion

“…A compelling body of literature has established the efficacy of tranexamic acid (TXA) for transfusion reduction in total joint arthroplasty (TJA) . However, the previously reported use of TXA (11‐46% of TJA patients) belies the published evidence of drug efficacy, possibly due to unsettled questions of drug safety .…”

Effects of Tranexamic Acid on Mortality and Blood Transfusion in Trauma Patients with Significant Hemorrhage: A Clinical Trial

“…A number of other studies propose that patients' conditions should be assessed prior to administration of Tranexamic acid in trauma-related hemorrhages. Thromboelastography is a method of evaluation prior to Tranexamic acid use (38)(39)(40)(41)(42)(43).…”