Is tranexamic acid use in patients with a hip fracture safe?

AIMS: To assess the safety of tranexamic acid (TXA) in a large cohort of patients aged over 65 years who have sustained a hip fracture, with a focus on transfusion rates, mortality, and thromboembolic events. METHODS: This is a consecutive cohort study with prospectively collected registry data. Patients with a hip fracture in the Region of Southern Denmark were included over a two-year time period (2015 to 2017) with the first year constituting a control group. In the second year, perioperative TXA was introduced as an intervention. Outcome was transfusion frequency, 30-day and 90-day mortality, and thromboembolic events. The latter was defined as any diagnosis or death due to arterial or venous thrombosis. The results are presented as relative risk (RR) and hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: A total of 3,097 patients were included: 1,558 in the control group and 1,539 in the TXA group.31% (n = 477) of patients had transfusions in the control group compared to 27% (n = 405) in the TXA group yielding an adjusted RR of 0.83 (95% CI 0.75 to 0.91). TXA was not associated with increased 30-day mortality with an adjusted HR of 1.10 (95% CI 0.88 to 1.39) compared to the control group as well as no association with increased risk of 90-day mortality with a per protocol adjusted HR of 1.24 (95% CI 0.93 to 1.66). TXA was associated with a lower risk of thromboembolic events after 30 days (RR 0.63 (95% CI 0.42 to 0.93)) and 90 days (RR 0.72 (95% CI 0.52 to 0.99)). A subanalysis on haemoglobin demonstrated a median 17.7 g/L (interquartile range (IQR) 11.3 to 27.3) decrease in the control group compared to 17.7 g/L (IQR 9.7 to 25.8) in the per protocol TXA group (p = 0.060 on group level difference). CONCLUSION: TXA use in patients with a hip fracture, was not associated with an increased risk of mortality but was associated with lower transfusion rate and reduced thromboembolic events. Thus, we conclude that it is safe to use TXA in this patient group. Cite this article: Bone Joint J 2021;103-B(3):449-455.

Introduction of national guidelines for restrictive blood transfusion threshold for hip fracture patients--a consecutive cohort study based on complete follow-up in national databases.

BACKGROUND: Randomized controlled trials have demonstrated that a restrictive red blood cell (RBC) transfusion strategy lowers transfusion frequency without affecting mortality. However, the external validity of these trials has not been tested in a large cohort. The purpose was to estimate the effect of introducing a National Clinical Guideline (NCG) for a restrictive hemoglobin transfusion threshold on transfusion frequency and mortality in hip fracture patients > 65 years old. METHODS: A consecutive cohort study of hip fracture patients > 65 years old residing in the southern region of Denmark was conducted using prospectively gathered data from registers during two separate 1-year time periods. The first period from October 1, 2012, to September 30, 2013, included 1494 patients and used a liberal transfusion threshold, whereas the second period from October 1, 2015, to September 30, 2016, including 1414 participants used a restrictive threshold from the NCG. Participant data for age, sex, body mass index, Charlson Comorbidity Index, time to surgery, and death were retrieved from the Danish Interdisciplinary Registry of Hip Fractures and were merged with RBC transfusion and medication data extracted from the Danish Transfusion and Odense Pharmacoepidemiological Databases, respectively. Cox proportional hazards models were used to test relative mortality risk for the restrictive group compared with the liberal group at 30 and 90 days. RESULTS: Overall RBC transfusions decreased from 42 to 30% (p < 0.001). The 30-day mortality rate (95% CI) was 9% (8;11) in the restrictive group and 13% (11;14) in the liberal group (p < 0.008), whereas the adjusted relative mortality risk was 0.72 (0.57;0.91). The 90-day mortality rate was 15% (13;17) in the restrictive group and 19% (17;21) in the liberal group, whereas the adjusted relative mortality risk was 0.78 (0.65;0.94). CONCLUSION: These data suggest that the introduction of an NCG on restrictive blood transfusion leads to lower transfusion frequency in hip fracture patients > 65 years old. Even though this reduction is associated with decreased mortality at both 30 and 90 days, it may be explained by other issues than restrictive transfusion strategy. There has been an improvement in the mortality of hip fracture patients in Denmark, and we suggest that a restrictive transfusion strategy does not lead to increased mortality.