Tranexamic Acid on Admission to Hospital in Hip Fracture Patients: A Scoping Review of Early Use for Reducing Blood Loss and Transfusion Risk

Abstract

Background: Hip fractures are a major cause of morbidity and mortality, particularly in the elderly, and the incidence is expected to rise significantly in the coming years. One of the key challenges in managing hip fracture patients is perioperative blood loss, which often necessitates allogeneic blood transfusion. Tranexamic acid (TXA), a synthetic antifibrinolytic agent, has been shown to reduce blood loss in various surgical settings, including elective orthopaedics. However, unlike elective surgery where bleeding begins intraoperatively, bleeding in hip fracture patients starts at the time of injury. This scoping review aimed to evaluate the existing literature on the use of early TXA administration, specifically at the point of admission, in patients with hip fractures. Methods: A comprehensive search of EMBASE and PubMed was conducted up to March 2025, and eight studies were identified that met the inclusion criteria, including three randomised controlled trials (RCTs). Six of these studies compared patients receiving TXA on admission to controls who received no TXA, involving a total of 840 patients. Most studies focused on extracapsular fractures in elderly, predominantly female patients. Results: Findings were mixed: four of the six studies found no statistically significant differences in haemoglobin levels or transfusion rates, while two RCTs demonstrated significantly reduced transfusion needs in the TXA group. Trends across studies suggested reduced blood loss and transfusion risk with TXA administered on admission. Importantly, no increase in complications, including venous thromboembolism, were observed. Conclusion: Early TXA administration in hip fracture patients appeared to be safe and may reduce transfusion requirements. Further high-quality research is warranted to determine the optimal timing and dosing strategy for TXA in this setting and to confirm the efficacy in reducing perioperative blood loss and transfusion risk.

1. Introduction

Hip fractures are associated with significant morbidity and mortality, particularly among the elderly population, frequently necessitating surgical intervention [1]. The incidence of hip fractures continues to increase, and it is estimated that by 2029, there will have been a 32% increase relative to 2021, which highlights the potential for a significant burden on future healthcare [2]. A common complication associated with hip fractures is blood loss, which can lead to perioperative anaemia and the need for allogeneic blood transfusions [3]. Blood transfusions, while potentially life-saving, carry inherent risks, including transfusion-related reactions, infections, and increased healthcare costs; thus, strategies aimed at minimising blood loss and reducing transfusion requirement are important in the management of hip fracture patients [3]. Tranexamic acid (TXA), a synthetic antifibrinolytic agent, has been shown to reduce blood loss in various surgical settings [4]. The underlying mechanism of action of TXA involves the reversible binding to plasminogen, thereby preventing the degradation of fibrin, a crucial component of blood clots; this antifibrinolytic effect helps stabilise clots and reduce bleeding [5]. The use of TXA in orthopaedic surgery, particularly in elective arthroplasty, has gained widespread acceptance, with numerous studies demonstrating its efficacy in reducing blood loss and transfusion rates [6]. Given that bleeding in hip fracture patients commences at the time of injury, unlike elective arthroplasty, where bleeding typically begins at the time of surgical incision, there is a growing interest in exploring the potential benefits of early TXA administration, ideally upon hospital admission.

The rationale for early TXA administration stems from the understanding that the most critical period for bleeding control is in the initial hours following the traumatic injury [7]. Initiating antifibrinolytic therapy as early as possible may help prevent the amplification of bleeding and reduce the overall blood loss volume [8]. Several studies have investigated the use of TXA in hip fracture surgery, but the timing of administration has varied, with some studies focusing on pre-operative or intra-operative administration [9]. The significance of early TXA administration is supported by data indicating that the majority of deaths from major bleeding occur within the first few hours of onset [10]. The CRASH-2 trial, a large-scale randomised controlled trial (RCT) involving trauma patients with significant bleeding, demonstrated that early administration of TXA, as compared to delayed administration, resulted in improved survival rates, emphasising the importance of timely intervention [11].

This scoping review aimed to comprehensively examine the existing literature on the use of TXA in hip fracture patients, with a specific focus on studies evaluating the impact of early, admission-time administration on blood loss and transfusion risk. This review systematically synthesised the available evidence, identified knowledge gaps, and provided insights into the potential benefits and limitations of early tranexamic acid use in this patient population.

2. Methodology

2.1. Search Strategy

A comprehensive search was conducted in EMBASE and PubMed from conception to March 2025. The following keyword strategy was applied:

(“Tranexamic Acid”[MeSH Terms] OR tranexamic acid[Title/Abstract] OR TXA[Title/Abstract])

AND

((“Hip Fractures”[MeSH Terms] OR “Femoral Neck Fractures”[MeSH Terms] OR hip fracture*[Title/Abstract] OR femoral neck fracture*[Title/Abstract] OR hip[Title/Abstract] OR femur[Title/Abstract]) AND facture*[Title/Abstract])

No filters were applied, including language restrictions. Citations were managed in Covidence software (Melbourne, Australia: Veritas Health Innovation).

2.2. Eligibility Criteria

• the study design was RCT, prospective or retrospective series
• the study must have included patients with hip fractures
• the study must have examined the use of TXA
• the study must have been in the English language

The following were excluded: studies without a full text, conference abstracts, reviews, and quality improvement studies.

To enhance the thoroughness of the literature review, Google Scholar’s citation tracking tool was employed to uncover studies that had cited the key articles identified through EMBASE, MEDLINE, and Cochrane. In addition, the bibliographies of all selected papers were hand-searched to identify any pertinent studies that may not have been captured through the primary database searches. Grey literature sources, such as relevant conference proceedings, dissertations, and pre-print servers, were also explored to reduce the possibility of publication bias. This multifaceted approach ensured a more exhaustive and unbiased collection of literature relevant to the use of TXA in hip fracture patients.

2.3. Study Selection

The process of study selection was conducted in adherence to the PRISMA Extension for Scoping Reviews guidelines (Supplementary Materials). Initially, all identified records from the database searches were imported into a reference management software to facilitate the removal of duplicate entries. Titles and abstracts of the remaining records were screened independently by two reviewers (RC and AC) based on predefined eligibility criteria.

Studies were included if they focused on hip fracture patients, evaluated the use of TXA, and reported on outcomes related to blood loss or transfusion requirements. Studies published in languages other than English were excluded due to resource constraints. Full-text articles were obtained for studies that appeared to meet the inclusion criteria based on title and abstract screening. Two reviewers (RC and AC) independently assessed the full-text articles for eligibility, with disagreements resolved through discussion and consensus.

2.4. Study Registration

This study was registered with Open Science Framework (osf.io/sd2qb).

3. Results

3.1. Study Characteristics

This scoping review identified eight studies [12,13,14,15,16,17,18,19] from the 198 identified studies using the search strategy that met the inclusion and exclusion criteria (Figure 1). There were seven studies, of which three were RCTs [15,16,18], and one Best Evidence Topic report [17] (

Table 1. Summary of the included studies.

Author and Year	Study Design	Number	Age/Sex (f%)	Fracture Type	Key Findings
Cui et al. [19] 2022	Retrospective	833 (control 126 vs. on admission 96)	77.3 vs. 78.8 yrs 67.5% vs. 62.5% female (control vs. TXA)	Intertrochanteric	No difference in haemoglobin concentration or transfusion day 1 postoperatively n = 11 (8.7%) vs. n = 8 (8.3%)
Doka et al. [13] 2024	Retrospective	64 (control 28 vs. 36 in ED TXA)	83.4 vs. 77.0 yrs 78.6% vs. 63.9% female (control vs. TXA)	Intracapsular (n = 12 vs. 16) Intertrochanteric (n = 16 vs. 20)	No difference in haemoglobin concentration day of surgery or on day 1 postoperatively. Lower transfusion in TXA group, but not significant (mean amount: 0.36 vs. 0.43)
Jiganti et al. [14] 2022	Retrospective	80 (single admission 40 vs. additional IO 40)	82.2 vs. 80.1 yrs 72.5% vs. 72.5% female (single vs. double)	Intertrochanteric (85.0% vs. 82.5%) Subtrochanteric (15.0% vs. 17.5%)	Single dose 17.5% transfusion and double dose 30%, and blood loss 1181 mls vs. 1390 mls, but neither was significantly different.
Ma et al. [15] 2021	Randomised control trial	125 (control 62 vs. admission 63)	78.7 vs. 78.1 yrs 64.5% vs. 66.7% female (control vs. TXA)	Intertrochanteric	Transfusion significantly (p = 0.036) reduced (n = 7 vs. 14) and greater haemoglobin and reduced hidden blood loss postoperative days 2&3 (p < 0.001) in the TXA group.
Moran et al. [12] 2022	Retrospective (not clearly stated)	508 (control 180 vs. 32 admission)	82.0 vs. 79.0 yrs 67% vs. 88% female (control vs. TXA)	Not clearly defined. Surgical procedures stated (for both intra and extracapsular fractures)	Transfusion n = 53/180 vs. 3/32 but unclear if significant as they focus on all four doses of TXA (admission, operative, postop): not clear where 4 doses came from.
Owen et al. [16] 2024	Randomised control trial	128 (64 control vs. 64 admission)	79.7 vs. 79.1 yrs 70.3% vs. 70.3% female (control vs. TXA)	Extracapsular	Transfusion not significantly (p = 0.65) reduced (n = 17 vs. 19). Powered for 25% reduction in transfusion risk.
Yakel et al. [18] 2023	Randomised control trial	89 (49 control vs. 40 admission)	79.2 vs. 82.2 yrs 71.4% vs. 72.5% female (control vs. TXA)	Extracapsular	Transfusion risk was significantly (p = 0.046) reduced (n = 18 vs. 7) in TXA group.

Tranexamic Acid (TXA).

). The size of the cohorts ranged from 64 [13] to 833 [19] patients. However, some of the larger cohorts included patients receiving TXA at multiple timepoints. For example, Cui et al. [19] and Moran et al. [12] reported cohorts of 833 and 508, respectively, but only 96 and 32 patients received TXA on admission, with controls (no TXA) of 126 and 180. The study by Jiganti et al. [14] was also included, which assessed whether the addition of a subsequent dose of TXA was beneficial following the admission dose. Overall, for the six studies comparing control (no TXA, n = 509) with TXA on admission (n = 331), there were 840 patients included. The age and gender distributions were typical of those observed in a general hip fracture population with a mean age of around 80 years and a female predominance (Table 1) [20]. The majority of studies only included extracapsular fractures, with only Doka et al. [13] including 28 intracapsular fractures in their cohort of 64 patients. Moran et al. [12] did not specifically state the fracture types included, but did state the operative management that included those indicated for intracapsular fractures.

3.2. Synthesis of Findings

The individual findings from four of the six studies comparing control with TXA on admission found no significant difference in haemoglobin concentration or transfusion risk/amount between the groups (Table 1). In contrast, Ma et al. [15] and Yakel et al. [18], both RCTs, found a significantly lower risk of requiring a blood transfusion (Table 1). Ma et al. [15] also showed significantly greater haemoglobin levels and reduced hidden blood loss on postoperative days 2 and 3 in the TXA group. Despite the other four studies not finding a significant difference, the majority demonstrated a trend towards a lower transfusion risk and blood loss with TXA on admission (Table 1).

3.3. Complications

For the included studies, there was no difference in the complication rates between those having TXA on admission and those who did not (

Table 2. Reported complications associated with TXA for the included studies.

Author and Year	Complications
Cui et al. [19] 2022	No difference in complications n = 6 (4.8%) vs. n = 3 (3.1%). No PE’s identified.
Doka et al. [13] 2024	No difference in adverse events but do not clearly state DVT/PE events.
Jiganti et al. [14] 2022	Complications were not discussed other than mortality, which was not different.
Ma et al. [15] 2021	No systemic complications related to TXA intervention and no cases of DVT/PE.
Moran et al. [12] 2022	No difference in major adverse events, which included DVT/PE, between the groups.
Owen et al. [16] 2024	No difference in rate of DVT/PE between groups. DVT n = 3 vs. 1, PE n = 1 vs. 0 (TXA vs. control)
Yakel et al. [18] 2023	No difference in mortality or complications between the different groups, DVT/PE not specifically reported.

Deep Vein Thrombosis (DVT), and Pulmonary Embolism (PE).

). More specifically, there was no difference or trend in the risk of venous thromboembolism.

3.4. Summary of Included Studies

Cui et al. [19] published their retrospective study on a preprint server. Although not formally recognised as a peer-reviewed publication, the authors chose to include their valuable work in this review. They evaluated the effectiveness of an optimised blood management programme in 833 elderly patients undergoing delayed surgery for intertrochanteric fractures. Patients were divided into four groups based on their blood management strategy. Group A (control) received no specific intervention. Group B received a single dose of intravenous TXA at admission. Group C received daily TXA (1 g/day) until one day before surgery. Group D received the same TXA regimen as Group C, with the addition of daily iron supplementation (200 mg), with or without recombinant human erythropoietin (rHuEPO; 40,000 IU). Primary outcomes assessed included preoperative hidden blood loss, allogeneic blood transfusion rates, haemoglobin change, and actual haemoglobin drop. Groups C and D showed significantly lower haemoglobin reduction, hidden blood loss, and hospital stay duration compared to Groups A and B. Additionally, Groups C and D had lower preoperative transfusion rates than Groups A and B. However, there was no significant difference in outcomes between Groups C and D. The findings suggest that sequential TXA administration was effective in reducing blood loss and transfusion needs, but the addition of iron supplementation did not confer additional clinical benefits over TXA alone.

Doka et al. [13] conducted a retrospective study investigating the impact of early administration of TXA in the emergency department (ED) on haemoglobin levels and outcomes in patients with fragility hip fractures. The study included 64 patients treated at a Level II trauma centre. Patients were divided into two groups: those who received 1 g of TXA in the ED within five hours of injury, and those who did not receive TXA in the ED. Their results showed no statistically significant differences in haemoglobin drop from ED arrival to the day of surgery (p = 0.322) or from ED arrival to postoperative day one (p = 0.339). While the TXA group showed a trend toward higher postoperative haemoglobin levels and fewer adverse events, these differences were not statistically significant (p = 0.178). Although the findings did not reach statistical significance, early administration of TXA in the ED appeared to be associated with improved haemoglobin outcomes and no increase in adverse events.

Jiganti et al. [14] undertook a retrospective cohort study to compare the effectiveness of one versus two doses of TXA in reducing perioperative blood loss. Eighty patients from a single institution were included: 40 received a single 1 g dose of TXA at hospital admission, while another 40 received the same initial dose plus a second 1 g dose administered intraoperatively at the time of incision. Baseline characteristics were well matched, but the twice-dosed group had a higher average BMI. After adjusting for BMI, the twice-dosed group had a slightly higher, though statistically insignificant, estimated total blood loss (115 mL difference; p = 0.40). Similarly, a higher proportion of patients in the twice-dosed group required blood transfusions (30% vs. 17.5%), but this difference was not statistically significant (p = 0.38). Hospital length of stay and 30-day mortality were also comparable between groups. Therefore, it would seem the second intraoperative dose of TXA in addition to a pre-admission dose did not result in a significant reduction in blood loss or transfusion rates compared to a single-dose regimen.

Ma et al. [15] conducted an RCT to investigate whether early intravenous TXA administration could reduce post-traumatic hidden blood loss. A total of 125 patients aged 65 or older, who presented within six hours of injury, were enrolled. Participants were randomly assigned to two groups: the TXA group (n = 63), which received 1 g of IV TXA at admission, and the control group (n = 62), which received an equal volume of saline. Haemoglobin and haematocrit levels were measured at admission and on post-traumatic days 1 through 3. They found that patients in the TXA group had significantly higher haemoglobin levels on postoperative days 2 and 3. Additionally, haematocrit levels and blood loss on postoperative days 1 to 3 were significantly lower in the TXA group. The need for preoperative blood transfusion was also notably reduced in the TXA group. Suggesting that early TXA administration in elderly patients with intertrochanteric fractures effectively reduced post-traumatic hidden blood loss and the requirement for preoperative transfusion, without increasing the risk of thrombotic events.

Owen et al. [16] also undertook an RCT aimed to evaluate the impact of TXA administered immediately upon hospital presentation in patients with extracapsular peritrochanteric hip fractures. A total of 128 patients were enrolled and randomised into two groups: one received intravenous TXA (a 1 g bolus over 10 min followed by a 1 g infusion over 8 h), and the other received a placebo (normal saline). Their results showed no statistically significant difference in transfusion rates between the TXA group (27%) and the placebo group (31%) (p = 0.65). Additionally, among those who required transfusion, the average number of units given was similar between groups (1.94 in TXA vs. 2.30 in placebo, p = 0.55). There was also no meaningful difference in estimated blood loss or the incidence of postoperative complications. Therefore, administering TXA at hospital presentation did not significantly reduce transfusion requirements, blood loss, or complications in elderly patients with extracapsular hip fractures.

Moran et al. [12] examined the optimal timing of TXA administration in patients with fragility hip fractures. During the study period, 508 eligible patients were admitted with fragility hip fractures and prospectively screened. Patients were grouped based on TXA administration: no TXA (n = 180), admission-only TXA (n = 32), arthroplasty-model TXA (incision and post-op; n = 112), and full 4-dose TXA (admission, incision, and post-op; n = 183). Patients ineligible for TXA due to medical contraindications were excluded. They showed that transfusion rates were significantly lower in the full 4-dose group (8.7%) and admission-only group (9.4%) compared to the incision and post-op group (25.7%) and the no-TXA group (29.4%) (p = 0.001). This highlights that early TXA administration, and more specifically at admission, was crucial in reducing transfusion requirements. Notably, patients who received TXA only at the time of admission had outcomes similar to those receiving the full 4-dose regimen.

Yakel et al. [18] undertook an RCT to investigate the effect of TXA on reducing blood transfusion rates and perioperative blood loss in patients with extracapsular hip fractures. The study included 100 patients with closed intertrochanteric or subtrochanteric femur fractures treated with intramedullary nailing. Upon hospital admission, patients were randomly assigned to receive either 1 g of intravenous TXA or a placebo (normal saline). After exclusions due to cancelled surgery, late administration, multiple injuries, or dropout, 89 patients were analysed (40 in the TXA group and 49 in the placebo group). The TXA group had a significantly lower transfusion rate of 17.5%, compared to 36.7% in the placebo group (relative risk 0.48; p = 0.046). Additionally, the TXA group experienced significantly less total blood loss, with a mean difference of 367 mL (p = 0.01). There were no significant differences between the groups in terms of intraoperative blood loss, hospital stay, 30-day mortality, or major complications. The study concludes that a single intravenous dose of TXA administered upon hospital admission effectively reduces both the need for blood transfusion and overall blood loss in patients with extracapsular hip fractures.

The Best Evidence Topic report by Williams and Butt [17] explored whether administering TXA in the ED for patients with a hip fracture reduced perioperative blood transfusions, blood loss, length of hospital stay, and mortality. They included four studies in their final analysis, which included RCTs [15,16,18], and one cohort study [12], all of which were included in the current review. They highlight key limitations. The findings were not easily generalisable to the broader hip fracture population, particularly frailer patients with intracapsular fractures, comorbidities, or delayed hospital presentations, groups most at risk of complications from blood loss. Furthermore, the studies varied in TXA timing and did not consistently report the interval between ED arrival, TXA administration, and surgery. They highlight the need for larger, well-designed trials to determine the effect of TXA on functional recovery, hospital stay, and mortality in the broader and more complex hip fracture population.

4. Discussion

This scoping review examined eight studies investigating the effects of administering TXA at the time of hospital admission in hip fracture patients. Seven were original research studies, of which three were RCTs and one was a Best Evidence Topic report. Cohort sizes varied significantly, from 64 to 833 patients, although the larger cohorts included patients who received TXA at various timepoints, not just on admission. Across the six studies comparing TXA on admission (n = 331) to no TXA (n = 509), the total sample size analysed was 840 patients. However, most studies focused predominantly on extracapsular fractures. Two RCTs demonstrated a significantly lower transfusion requirement in the TXA group. Ma et al. [15] also observed significantly higher haemoglobin levels and reduced hidden blood loss on postoperative days 2 and 3 in the TXA group. Although not all findings reached statistical significance, most studies suggested a trend towards reduced blood loss and transfusion risk with TXA given on admission. Importantly, no increase in complication rates, including venous thromboembolism, was observed in patients who received TXA on admission compared to those who did not. This supports the safety of early TXA administration in this patient population. Overall, while evidence was mixed, there was a favourable trend supporting the use of TXA on admission to reduce transfusion needs without increasing adverse events.

The efficacy of TXA in mitigating blood loss and transfusion needs during hip fracture surgery has been investigated; however, the optimal timing and dosage of TXA administration remain a subject of ongoing research [21]. A systematic review and meta-analysis of multiple studies in trauma and surgery has replicated these results, suggesting a potential benefit of higher TXA doses in further decreasing blood loss, transfusion rates, and mortality [22]. These findings may be especially important, given the importance of early administration of TXA [22]. Prior to its use as a treatment for traumatic bleeding, TXA had already been employed in surgical settings and for managing heavy menstrual bleeding [8]. This review has shown that the early administration of TXA upon hospital admission shows promise in reducing transfusion rates among geriatric patients with hip fractures. The administration of TXA has been shown to improve outcomes in trauma patients by reducing blood transfusion requirements [23]. The drug’s mechanism of action involves inhibiting fibrinolysis, which can be particularly beneficial in the context of trauma and surgical procedures where excessive bleeding is a concern [24]. Clinical trials, such as the CRASH-2 trial, have demonstrated that early administration of TXA in trauma patients can significantly reduce mortality due to bleeding [7]. Similarly, the CRASH-3 trial suggests that TXA is safe for patients with traumatic brain injuries, especially if administered within three hours of the injury [25].

The importance of early TXA administration is supported by evidence from military settings, where its use in trauma care has become increasingly prevalent [26]. The existing body of evidence supports the use of TXA in various clinical scenarios to reduce bleeding and improve outcomes, and now there is a basis to explore the use of TXA upon admission for hip fracture patients [27]. One of the major limitations of the studies reporting the use of TXA in hip fracture patients is the reporting of time from injury to administration of TXA, with the majority simply administering this at the time of hospital admission. The CRASH-2 trial established that administration of TXA after 3 h from injury, in all trauma patients, was unlikely to be effective [7]. Whether this applies to hip fracture patients is not clear, and further work is required to establish the optimal time window for administration.

5. Conclusions

This scoping review supports the safety of early TXA administration in patients presenting with a hip fracture, and more specifically, those sustaining an extracapsular fracture. Overall, while evidence is mixed, there is a favourable trend supporting the use of TXA on admission to reduce transfusion needs, and it appears not to increase adverse events. Further high-quality RCTs focusing specifically on early TXA administration are needed to strengthen the evidence base.