TXA Use in Adolescent Patients Undergoing Sarcoma Surgery

Commentary Tranexamic acid (TXA) has been widely utilized in several clinical settings, such as trauma, joint arthroplasty, neurosurgery, and cardiac surgery, for its potent anti-bleeding efficacy, which has been shown to reduce intraoperative and postoperative blood loss as well as red blood-cell transfusion requirements1. As an antifibrinolytic drug, TXA stabilizes the blood clot by inhibiting the process of fibrinolysis. It has been used clinically for >50 years without obvious evidence of any increased risk of thromboembolic adverse events. TXA is currently on the World Health Organization List of Essential Medicines2. In spite of its potent anti-bleeding efficacy and excellent safety, investigators have continued to provide conflicting updates on its application and efficacy in different clinical settings3. In adult joint arthroplasty and pediatric spinal surgery, TXA has been confirmed to reduce perioperative bleeding without obvious side effects in randomized controlled trials4–7. Until now, there had been no high-quality randomized controlled trial on the use of TXA in the pediatric orthopaedic oncology population. It is especially important and interesting to study the efficacy and safety of TXA in these patients given the large amount of blood loss that occurs in tumor surgery. El Ghoneimy et al. designed an excellent double-blinded placebo-controlled study to assess the safety and efficacy of the intraoperative use of TXA in children and adolescents undergoing limb-salvage surgery. The authors included 48 patients with a femoral sarcoma, with 24 patients in each group. Despite the small cohort size, their results are relatively reliable due to their excellent study design. The study was a double-blinded placebo-controlled trial that achieved 80.7% statistical power. They narrowed patient selection by only including specific children and adolescents with osteosarcoma or Ewing sarcoma of the femur who underwent neoadjuvant chemotherapy and limb-salvage surgery, which significantly decreased selection bias. Perioperative blood loss can be more readily compared between 2 groups when obvious bias from other factors, such as tumor location and type, chemotherapy type, and surgery type, is absent. Interestingly, the authors found that TXA reduced perioperative blood loss and perioperative blood transfusion without having a significant effect on intraoperative blood loss and intraoperative blood transfusion, which conflicts with previous retrospective studies8,9. However, the p value for the comparison of intraoperative blood loss was 0.06, which was close to significance despite the relatively small sample size. This difference may become significant with a larger sample size. There is also debate regarding the role of intravenous TXA in reducing intraoperative blood loss in elective surgeries. Mechanistically, TXA reduces bleeding by stabilizing clots in blood vessels. An occlusive blood clot can be quickly formed in smaller vessels instead of in large vessels to stop bleeding during and after surgery. Besides oozing, intraoperative bleeding is also from large blood vessels, which require suturing or cauterization rather than an occlusive blood clot in order to stop bleeding. The bleeding from large blood vessels can vary considerably due to differences in tumor size, tumor type, tumor location, and surgical technique, among other factors, which may account for the differences in reported intraoperative blood loss across various studies in the literature. In the absence of bleeding from large blood vessels, postoperative bleeding can be efficiently reduced with intraoperative TXA because of the efficacy of the drug in stabilizing the occlusive blood clot in small vessels to stop the bleeding in the severed muscle, soft tissue, and bone. However, a more robust study design focusing on a single tumor type of a similar size located in a similar area of long bone, with a larger patient cohort, is needed to obtain more objective proof. Overall, in spite of its limitations, this study supplied a relatively reliable conclusion: the use of TXA to reduce perioperative blood loss and perioperative blood transfusion is safe in children and adolescents under the age of 18 years who are undergoing limb-salvage surgery for sarcoma of the femur.