Intravenous tranexamic acid and thromboembolic events in hip fracture surgery: A systematic review and meta-analysis

Background: Osteoporotic hip fractures are a major health problem in developed countries. Surgical management is the mainstay of treatment for these injuries, and historically presents an increased risk of thromboembolism, blood loss and blood transfusion. Despite the demonstrated safety of tranexamic acid (TXA) in elective hip arthroplasty, there is uncertainty regarding the risk of thromboembolism with the administration of TXA during hip fracture surgery. This study aims to address the following questions regarding patients undergoing traumatic hip fracture surgery: 1. Does intravenous TXA increase the risk of thromboembolic events? 2. Does intravenous TXA reduce peri-operative blood loss? 3. Does intravenous TXA increase the risk of non-thromboembolic complications or post-operative mortality?

Methods: A literature search of Ovid MEDLINE, Embase, PubMed, the Cochrane Register of Controlled Trials and CINAHL was conducted, assessing results from database inception until the 11th May, 2021. We included randomised controlled trials that investigated perioperative administration of intravenous TXA in patients undergoing hip fracture surgery, compared to a control cohort. We excluded articles published in a language other than English, evaluated elective hip arthroplasty, or did not report thromboembolic events. Included trials were analysed using RevMan v5.3.

Results: Sixteen articles encompassing 1491 patients met inclusion criteria. The risk difference of thromboembolic events in the TXA group was 0.02 (95%C.I. -0.01-0.04; p=0.17). TXA reduced post-operative transfusion rates by 42% (range: 28-54%, p<0.0001). The mean haemoglobin was higher in the TXA group on post-operative day one (0.77g/dL, p<0.0001), day two (0.56g/dL, p<0.0001) and day three (0.42g/dL, p<0.0001). There was no statistically significant difference in non-thromboembolic complications or post-operative mortality across the two cohorts.

Discussion: There is no conclusive evidence from the current published literature that peri-operative intravenous TXA administration increases the risk of thromboembolic events after hip fracture surgery. This meta-analysis reinforces that TXA is effective in reducing post-operative transfusions and haemoglobin decline after hip fracture surgery. This study found that TXA did not increase non-thromboembolic complications or post-operative mortality. Further large-scale studies evaluating thromboembolic complications as a primary outcome are required to definitively establish the safety of TXA in hip fracture surgery.

Level of evidence: I; meta-analysis of randomised controlled trials.