Intertrochanteric fractures are common among older patients, typically resulting from low-energy trauma or falls. As the aging population grows, the incidence of these fractures continues to rise, and they are associated with substantial perioperative blood loss and a higher risk of postoperative complications (Tüzün et al., 2022). Closed reduction and internal fixation with a proximal femoral nail antirotation (PFNA) is a common surgical approach for treating intertrochanteric fractures, effectively stabilizing the fracture and promoting healing (Tang et al., 2023). However, perioperative blood loss, encompassing both intraoperative and hidden components, remains a significant clinical concern and contributes to increased transfusion requirements and postoperative complications such as thromboembolism and infection, which can adversely affect recovery (Cho et al., 2022).

Tranexamic acid (TXA), an antifibrinolytic agent, is widely used in orthopaedic surgery to reduce bleeding. By inhibiting fibrinolysis, TXA has been shown to reduce blood loss during procedures such as hip fracture surgery. TXA can be administered intravenously or topically (Dionne et al., 2022). Intravenous TXA rapidly enters the systemic circulation and reduces overall blood loss, but has raised concerns about potential systemic complications such as deep vein thrombosis (DVT) (Taeuber et al., 2021). Topical administration, on the other hand, delivers the drug directly to the surgical site, thereby reducing systemic exposure and potentially minimizing the risk of complications (Juraj et al., 2021).

While the effectiveness of TXA in reducing blood loss during hip fracture surgery is well established, direct comparisons among intraoperative TXA regimens remain limited, especially in older adults. In addition, it is unclear whether the effects of different regimens vary across age strata, with particular uncertainty in very old patients. To address these gaps, we conducted a multicenter retrospective study comparing perioperative outcomes among four TXA strategies, namely combined intravenous (IV) and topical TXA, IV TXA alone, topical TXA alone, and no TXA, in older adults undergoing PFNA for intertrochanteric fractures. We further explored potential effect heterogeneity across prespecified age strata.

A total of 1,228 patients with intertrochanteric fractures were included and classified into four groups according to the intraoperative TXA regimen. The IV plus Top group received combined intravenous and topical TXA (n = 293), the IV group received intravenous TXA only (n = 321), the Top group received topical TXA only (n = 309), and the control group did not receive TXA (n = 305). Baseline demographic and clinical characteristics are summarized in Table 1. The four groups differed significantly in treatment center (P < 0.001), age (P < 0.001), prevalence of hypertension (P = 0.027), fracture classification (P = 0.027), and preoperative hemoglobin level (P < 0.001). The remaining variables were generally comparable, with no statistically significant differences. After application of IPW, baseline characteristics were well balanced across the groups (Supplementary Figure S1; Supplementary Table S1).

Table 2 summarizes perioperative blood loss and transfusion outcomes across the four treatment groups. Overall, TXA use was associated with significantly lower IBL, HBL and TBL compared with no TXA (all P < 0.001). The greatest reductions in TBL were observed in the IV + Top group, which had lower TBL than the control group and than either single route group, whereas TBL did not differ significantly between the IV and Top groups. Differences in TBL were largely driven by HBL. All TXA regimens reduced HBL compared with the control group, with the IV + Top group showing the lowest HBL and significantly lower HBL than both the IV and Top groups, and HBL in the Top group was also lower than in the IV group. In contrast, differences in IBL were smaller, and only the IV + Top and IV groups had significantly lower IBL than the control group, with no meaningful differences among the other pairwise comparisons (Supplementary Table S2). Transfusion outcomes showed a clear advantage only for the combined regimen. There were significant differences between groups in both transfusion rates and transfusion volumes (P < 0.001), and in pairwise comparisons the IV + Top group had lower transfusion rates and volumes than all other groups. The Top group had a modest reduction in transfusion volume compared with controls (P = 0.024), whereas transfusion rates did not differ significantly (P = 0.054), and other pairwise differences were not statistically significant (Supplementary Table S3).

Table 3 summarizes postoperative complications across the four treatment groups. There were no significant differences in the incidences of deep vein thrombosis, wound complications, postoperative pneumonia, 30 days mortality or 90 days mortality among the groups (all P > 0.05). In contrast, postoperative length of stay differed significantly between groups (P = 0.040). In pairwise comparisons, postoperative length of stay was shorter in the IV + Top group (P = 0.010) and the Top group (P = 0.016) than in the control group. In this cohort of older adults with intertrochanteric fractures, perioperative TXA use was not associated with a higher incidence of thrombotic events or other major postoperative complications.

Patients were divided into three age subgroups (65–74 years, 75–84 years and 85 years or older). We first fitted a generalized linear regression model with TBL as the dependent variable. In this model, treatment group (P < 0.001), age group (P < 0.001), surgical time (P < 0.001) and the interaction between age group and treatment group (P = 0.009) were all significantly associated with TBL (Supplementary Table S4). To further describe TBL across treatment and age groups, we calculated estimated marginal means for TBL, which are presented in Table 4. These estimates suggested age related variation in TBL and in the absolute blood sparing effect of TXA. Although absolute blood loss increased with age, the blood sparing advantage of TXA, particularly in the intravenous plus topical treatment group, appeared to be maintained across all age groups. We did not find clear evidence that the treatment effect diminished with increasing age.

In addition, we fitted a logistic regression model with transfusion rate as the dependent variable. In this model, the IV + Top treatment group (P < 0.001) and the Top treatment group (P = 0.029) had significantly lower transfusion rates than the control group. Preoperative hemoglobin level (P < 0.001) and surgical time (P = 0.002) were also significantly associated with transfusion rate. The interaction between treatment group and age group was not statistically significant (Supplementary Table S5). To further describe transfusion rate across treatment groups and age groups, we calculated estimated marginal means of transfusion rate, which are presented in Table 5.

In this multicenter retrospective cohort study of older adults undergoing intramedullary nail fixation for intertrochanteric fractures, we found that perioperative TXA use significantly reduced perioperative blood loss, transfusion rates and transfusion volumes, with combined intravenous and topical administration associated with the largest reductions. Across the entire cohort and within each age subgroup, patients treated with TXA had lower TBL than those who did not receive TXA, and the combined regimen produced the greatest reductions in both TBL and HBL (Zhou et al., 2019). In addition, TXA use was not associated with a higher incidence of venous thromboembolism or other major postoperative complications (Ghorbani et al., 2024), and combined intravenous and topical administration was associated with a shorter postoperative length of stay. These findings extend previous research by directly comparing three commonly used intraoperative TXA regimens with a no TXA group in a real world population of patients with intertrochanteric fractures treated with intramedullary nails. Overall, our results support a blood sparing benefit of TXA, particularly with combined intravenous and topical administration, and suggest that this benefit is preserved even in very old patients.

These findings are largely consistent with previous studies in hip fracture surgery, which have shown that TXA can reduce perioperative blood loss and generally decrease the need for transfusion (Lei et al., 2017). Prior studies focusing on intertrochanteric fractures have predominantly examined single route administration of TXA and have compared it with placebo or standard care. These studies typically report reduced blood loss without a clear increase in clinically relevant DVT (Liu and Lee, 2025). However, there is limited evidence directly comparing different TXA strategies in patients with intertrochanteric fractures treated with PFNA. In our study, combined intravenous and topical administration was more effective in reducing both TBL and HBL than either route alone, which is consistent with the hypothesis that systemic and local antifibrinolytic effects may provide complementary benefits (Yuan et al., 2018). In addition, combined intravenous and topical TXA reduced transfusion rates and volumes more than TXA given by either route alone (Haj-Younes et al., 2020). To our knowledge, previous studies have not systematically examined age as a modifier of the effects of different TXA regimens. Our results suggest that the blood sparing benefit of TXA is preserved across age strata, including very old patients, and that its ability to reduce perioperative transfusion rates does not appear to diminish with increasing age.

Based on the observed reduction in blood loss and transfusion volume, our findings are clinically significant and can be applied to perioperative blood management in elderly patients with intertrochanteric fractures. First, the consistent reduction in TBL and HBL with TXA supports its use as part of standard care pathways for intramedullary fixation, particularly in settings where perioperative anaemia and transfusion are common and associated with adverse outcomes. Stabilising haemoglobin levels may facilitate earlier mobilisation, reduce physiological stress and support smoother postoperative recovery (Lawrence et al., 2003). Second, the more favourable blood sparing profile of the IV plus Top regimen suggests that combined administration may be a reasonable option when the goal is to minimise blood loss, especially in patients with limited cardiopulmonary reserve or restricted access to blood products. Third, the preservation of TXA benefit across age strata indicates that advanced age alone should not preclude its use when standard thromboprophylaxis is provided. In the oldest patients, who often have the highest bleeding and transfusion risk, even modest reductions in blood loss may translate into clinically meaningful benefits (Willems et al., 2012). Clinicians should still individualise decisions, balancing bleeding and thrombotic risk, comorbidities and patient preferences, but our data suggest that TXA appears to be a generally safe and effective adjunct in this population.

Several limitations warrant consideration when interpreting these findings. The retrospective observational design means that the findings are subject to residual confounding and selection bias. Because TXA regimen selection was non-random, baseline imbalances could have biased unadjusted comparisons. Older age and lower preoperative hemoglobin are associated with a higher likelihood of transfusion and postoperative complications, and differences in fracture classification may reflect varying injury severity and surgical complexity, which can increase blood loss independent of TXA. These factors could therefore overestimate or underestimate regimen effects if higher-risk patients preferentially received (or were withheld) TXA. We used stabilized IPW and confirmed improved post-weighting balance, but residual confounding from unmeasured factors cannot be fully excluded; accordingly, our findings should be interpreted as associations. TXA use and choice of regimen were not randomised and instead reflected institutional protocols and surgeon preference, which may have been correlated with unmeasured factors such as perceived bleeding risk, frailty or intraoperative findings. Unmeasured clinician judgment and patient frailty may have influenced both regimen selection and the risks of transfusion and postoperative complications, resulting in confounding by indication that inverse probability weighting cannot fully eliminate. Although baseline demographic and clinical characteristics were broadly similar across groups, we cannot rule out the influence of unrecorded confounders, including subtle differences in surgical technique, intraoperative haemostasis or postoperative rehabilitation. Detection of venous thromboembolism and other complications relied on routine clinical assessment rather than systematic screening, so asymptomatic events may have been missed. This limitation could lead to underestimation of the true incidence of deep vein thrombosis and may reduce the power to detect modest differences in safety outcomes. In addition, the study was conducted in four hospitals within a single health system, and all patients underwent a specific surgical and anaesthetic approach, which may limit generalisability to settings with different perioperative protocols or patient populations. Finally, although the overall sample size was substantial, some subgroup analyses, particularly in the oldest age group and for infrequent complications, may still have been underpowered.

Despite these limitations, this multicentre cohort provides pragmatic evidence that TXA, particularly when administered as a combined intravenous and topical regimen, is associated with substantial reductions in perioperative blood loss in older adults undergoing intramedullary fixation of intertrochanteric fractures, without a clear increase in thromboembolic events or other major postoperative complications. Analyses stratified by age suggest that this blood sparing effect is preserved across older age groups, including patients aged 85 years and above. Future research should aim to confirm these findings in prospective or randomised studies that directly compare different TXA regimens, explore optimal dosing and timing and incorporate systematic assessment of venous thromboembolism and other adverse events. Trials that focus on very old patients at high risk, and that evaluate longer term outcomes such as functional recovery, quality of life, rehospitalisation and mortality, would be particularly informative. Long-term prognosis after proximal femur fracture remains poor. A 5 year follow-up study of patients aged 65 years and older reported 1 year and 5 year survival rates of 88.9% and 66.7%, with substantially lower survival among those aged 90 years and older, largely driven by comorbidity burden (Hashimoto et al., 2023). In addition, cost effectiveness analyses and implementation studies could help define how best to integrate TXA based blood management strategies into routine care for intertrochanteric hip fractures.