Efficacy of topical tranexamic acid within a blood-saving programme for primary total hip arthroplasty: a pragmatic, open-label randomised study

Abstract

Background

Total hip arthroplasty entails considerable peri-operative blood loss, which may lead to acute post-operative anaemia and red blood cell transfusion. This study was aimed at assessing whether the addition of topical tranexamic acid to our ongoing blood-saving protocol for total hip arthroplasty was effective and safe.

Materials and methods

A pragmatic, prospective, open-label randomised study of patients scheduled for total hip arthroplasty at a single centre was conducted. Consecutive patients were randomly assigned to receive topical tranexamic acid (2 g) at the end of surgery (tranexamic group, n=125) or not (control group, n=129). A restrictive transfusion protocol was applied. Outcome measures were red blood cell loss at 24 hours after surgery, in-hospital transfusion rate, and incidence of thromboembolic complications.

Results

Topical tranexamic acid was effective in reducing both red cell loss (mean difference: 138 mL [95% CI 87–189 mL]; p<0.001) in the 24h after surgery and in-hospital transfusion rates (12 vs 32.6%, for the tranexamic acid and control groups, respectively; p<0.001; relative risk=0.37 [95% CI 0.22–0.63]). However, relative red cell loss and transfusion rates were higher in females than in males, irrespectively of tranexamic acid use. The beneficial effect of tranexamic acid on transfusion was restricted to patients with pre-operative haemoglobin ≥13 g/dL (5.1 vs 24.8%; p<0.001). Topical tranexamic acid was well tolerated and no clinically apparent thromboembolic complications were witnessed.

Discussion

The use of topical tranexamic acid after hip arthroplasty reduced red cell loss and transfusion rates; the efficacy of this strategy may be improved by reinforcing both pre-operative haemoglobin optimisation and adherence to the practice of transfusing single units of red cells.

Introduction

Total hip arthroplasty (THA) is a successful, well-standardised and safe surgical procedure that is increasingly used as part of routine practice in orthopaedic surgery. The estimated average blood loss in THA is 1,500 mL, but it is frequently underestimated¹. As a result, a significant proportion of THA patients may require post-operative red blood cell (RBC) transfusion (RBCT), although there is considerable between-centre variability depending mostly on the transfusion thresholds and blood management protocols of each institution^2–4.

RBC are a costly and scarce resource and RBCT is not free of risks (e.g., transmission of blood-borne infectious diseases, haemolytic reactions, circulatory overload, acute lung injury, coagulopathy)⁵. An especially relevant complication is transfusion-related immunomodulation, which may increase the risk of post-operative infection and even mortality⁶. Disadvantages of RBCT have led to the development of multidisciplinary and multimodal “patient blood management” programmes, which refer to the timely application of evidence-based medical and surgical concepts designed to stimulate erythropoiesis, optimise haemostasis and minimise blood loss in an effort to maintain haemoglobin concentration, reduce transfusion requirements and improve patients’ outcome^7–9. As a result, a progressive decline in the incidence of RBCT in THA has been observed¹⁰.

Tranexamic acid (TXA), a synthetic lysine analogue, competitively blocks plasminogen-binding sites on the surface of fibrin and slows down the conversion of plasminogen into plasmin, thus reducing fibrinolysis and blood loss. In major orthopaedic surgery, the intravenous administration of anti-fibrinolytic drugs, mostly TXA, either as a single, pre-operative dose or multiple, peri-operative doses, has been shown to reduce RBCT rates by more than 60%^11,12. Although isolated cases of thromboembolic complications have generated concern about the risk associated with the use of TXA¹³, a recent meta-analysis considered this risk as negligible, even when the agent is given to high-risk patients¹⁴. Compared to intravenously administered TXA, topically delivered TXA would have lower systemic absorption and, theoretically, be associated with an even lower risk of thromboembolic events. Data from several publications strongly suggest that topical use of TXA in THA is a safe and effective treatment for reducing post-operative blood loss and RBCT requirements^15–18.This prospective study was aimed at assessing whether topical TXA administration within our ongoing blood-saving protocol would reduce post-operative blood loss and decrease RBCT needs in primary THA, without increasing the risk of thromboembolic complications.

Material and methods

Study design

A prospective, open-label randomised study of patients scheduled for primary THA surgery at the “Miguel Servet” University Hospital during a 2-year period was conducted. Patients were screened for study eligibility and enrolment by an orthopaedic surgeon (NPJ, JM) on the occasion of their pre-operative admission. According to medical record number, consecutive THA patients fulfilling eligibility criteria were randomly assigned to receive topical TXA at the end of surgery (tranexamic group, even numbers) or not (control group, odd numbers). The study was reviewed, approved and registered by the Committee of Research Ethics of the Autonomous Community of Aragón, Spain (C.P IACS 93/013-C.I. PI 11/89). All patients signed informed consent to enter the study.

Inclusion and exclusion criteria

Only cemented or non-cemented primary elective THA were included. Patients were excluded if presenting with hyper- or hypo-coagulability disorders, known allergy to TXA, intravenous iron, folic acid or recombinant human erythropoietin, epilepsy or hip fracture. A history of thromboembolic events and/or previous or ongoing anticoagulant treatment was not an exclusion criterion, as eliminating patients at higher risk might have introduced a bias in safety results. Patients with incomplete data sets were excluded from analysis.

Peri-operative management

All patients were operated on by the same surgical team, under standardized anaesthesia, antibiotic prophylaxis, and post-operative analgesia. Two types of implants were used (ABG II, Stryker Corporation, Kalamazoo, MI, USA; VerSys, Zimmer Inc., Warsaw, IN, USA). Usually, two closed-suction drains were placed after wound closure (one subfascial, one subcutaneous) and were removed the next morning after the operation. The post-operative blood loss in the vacuum collectors was recorded. All patients stayed in the post-anaesthesia recovery unit for at least 4 h before being transferred to the ward. Thromboprophylaxis was provided by once-daily, weight-adjusted dosing of low molecular weight heparin (Enoxaparin, Clexane, Sanofi-Aventis S.A., Barcelona, Spain), which was started 12 h after surgery and maintained for the first 30 post-operative days.

Tranexamic acid administration

In the study group, topical TXA (2 g; Amchafibrin, Meda Pharma S.L., Madrid, Spain) was administered following skin closure through the deeper drainage tube, which was subsequently clamped during the first 30 minutes after TXA dosing.

Stimulation of erythropoiesis

All patients received: (i) three doses of intravenous iron (200 mg, Venofer, Vifor, Saint Gallen, Switzerland), starting on admission; (ii) vitamin B₁₂ (1 mg) on admission; and (iii) folic acid (5 mg/day) for the entire duration of hospitalisation. Patients with pre-operative haemoglobin levels of less than 13 g/dL also received a single dose of recombinant human erythropoietin (40,000 IU, sc; Eprex, Janssen-Cilag, Madrid, Spain) 24 h before surgery¹⁹.

Transfusion protocol

The anaesthesiologist made decisions on transfusion, both in the operating theatre and in the anaesthesia recovery unit. On the ward, measurement of post-operative blood loss and decisions on postoperative transfusions were made by the attending surgeon. In these orthopaedic patients, transfusion was indicated when the patients had symptoms of acute anaemia (hypotension, tachycardia, tachypnoea, dizziness, fatigue, etc.) and/or had a drop in haemoglobin level below 8 g/dL if they had no risk factors; or below 9 g/dL if they had ischaemic cardiomyopathy or severe peripheral vascular disease⁷. This transfusion protocol was approved by the hospital blood transfusion committee, and it was applied by the anaesthesiologists and surgeons to all patients in the operating theatre, the anaesthesia recovery unit, and the ward for the entire duration of hospitalisation.

Data collection

A set of demographic and clinical data was prospectively gathered for all patients, including gender, age, weight, height, body mass index, ASA physical status scale, thromboembolic events and/or previous anticoagulant treatment, surgical procedure (anaesthesia, duration, drainage debit), peri-operative coagulation parameters and haemoglobin concentrations, RBCT rate (percentage of transfused patients) and index (RBCT units per patient) (primary outcome measure), pre-RBCT haemoglobin, post-operative thromboembolic complications (secondary outcome measure), post-operative infectious complications, adverse reactions to treatment (metallic taste, headache, nausea, vomiting, hypotension, anaphylactic reactions, seizures), in-hospital mortality, and duration of hospital stay. Prosthetic complications occurring within 60 days after surgery were also recorded.

We used the Nadler’s formula to calculate the patients’ blood volume and derived the total RBC volume from multiplying the volume of blood by the corresponding haematocrit level. The overall peri-operative RBC mass loss on post-operative day 1 (primary outcome measure) was calculated by subtracting the RBC volume on post-operative day 1 from the pre-operative RBC volume and adding the total RBC volume transfused^2,3 (1 RBC unit ≈ 155 mL of RBC). To adjust baseline differences in total RBC volume, the RBC volume lost was also analysed as a percentage of the patient’s baseline total RBC volume (relative RBC volume loss)^2,3.

Thromboembolic complications were systematically searched for clinically. If a thromboembolic complication was suspected to be present on a clinical basis, it had to be confirmed instrumentally (e.g., venous Doppler scan for deep venous thrombosis, computerised tomography angiography for pulmonary thromboembolism).

Statistics

The sample size was estimated by considering that topical TXA application could halve the incidence of post-operative RBCT (36% at that time). For this primary end point, we calculated that a total of 113 patients per arm would provide a 90% power (β error) and a two-sided level of significance of 0.05 (α error). A 5% loss during follow-up was assumed.

Data were expressed as percentages or as the mean ± standard deviation. Pearson’s chi-square test or Fisher’s exact test was used for comparison of qualitative variables. Parametric two-way analysis of variance or the non-parametric Kruskal-Wallis test was used for comparison of quantitative variables, after consideration of distributional characteristics. These tests were used for both primary and subgroup analyses. All statistics were performed with computer software (IBM SPSS 24.0, Chicago, IL; licensed to the University of Málaga, Málaga, Spain), and a p value of less than 0.05 was considered statistically significant.

Results

A total of 327 patients underwent primary THA during the study period. Of these 35 were initially excluded (34 hip fractures, 1 history of epilepsy). Of the remaining 293, 151 were assigned to the control group and 142 to the study group (topical TXA). During follow-up, 39 were excluded because of non-compliance with the study protocol (7 from the control group and 4 from the study group), or incomplete records (15 from the control group and 13 from the study group). Therefore, 254 patients were included in the analysis (129 from the control group and 125 from the study group) (Figure 1).

Figure 1.

Patients’ flow diagram.

The two groups were homogeneous regarding demographic, clinical and surgical characteristics, except for gender, with more women in the TXA group (Table I). There were also no differences in post-operative complication rates or duration of hospital stay (Table I). No clinically apparent thromboembolic complications were detected during the 60-day follow-up period.

Table I.

Demographic and clinical characteristics of the patients.

	Control group (n=129)	TXA group (n=125)	p
Gender, n (%)			0.012
Male	80 (62.0)	57 (45.6)
Female	49 (38.0)	68 (54.4)
Age (years)	67±12	67±12	0,845
BMI (kg/m2)	29.1 (4.7)	28.6 (4.4)	0,358
THA indication, n (%)			0.270
Coxarthrosis	111 (86.0)	109 (87.2)
Aseptic necrosis	17 (13.2)	12 (9.6)
Dysplasia	1 (0.8)	4 (3.2)
THA type, n (%)			0.568
Cemented	69 (53.3)	61 (48.8)
Non-cemented	55 (42.6)	56 (44.8)
Hybrid	5 (3.9)	8 (6.4)
Previous TED, n (%)	1 (0.7)	1 (0.8)	0.982
Oral anticoagulation, n (%)	5 (3.9)	4 (3.2)	0.771
ASA status, n (%)			0.493
I/II	107 (82.9)	98 (78.4)
III/IV	22 (17.1)	27 (21.6)
Anaesthesia, n (%)			0.241
Spinal	129 (100)	123 (98.4)
General	0 (0)	2 (1.6)
Surgical time (min)	106±20	106±18	0.952
Number of drains, n (%)			0.407
1	25 (19.4)	19 (15.2)
2	103 (79.8)	106 (84.8)
Post-op complications, n (%)	4 (3.1)	7 (5.6)	0.328
LHS (days)	7 (2)	7 (2)	0.963

Values are mean (SD) or number (proportion). ASA: American Society of Anesthesiologists physical status scale; BMI: body mass index; LHS: length of hospital stay; Post-op: post-operative; TED: thrombo-embolic disease; THA: total hip arthroplasty; TXA: topical tranexamic acid; p: p-value.

Despite similar pre-operative levels, the haemoglobin level on post-operative day 1 was higher in the topical TXA groups than in the control group, reflecting a reduction in post-operative blood loss (Table II). When analysed in terms of RBC mass, topical TXA application resulted in a reduction of both absolute (mean difference: 189 mL [95% CI 128–250 mL]; p<0.001) and relative (mean difference: 9.7% [95% CI 6.2–13.1%]) peri-operative RBC mass loss, as measured 24 h after surgery (Table II). Interestingly, this reduction was observed for both RBC mass lost through wound drains (mean difference: 26 mL [95% CI 13–40 mL]; p<0.001) (Table II) and surgical/hidden RBC mass losses (mean difference: 163 mL [95% CI 103–222 mL]; p<0.001).

Table II.

Haemoglobin levels, blood loss and red blood cell transfusion.

	Control group (n=129)	TXA group (n=125)	p
Pre-op Hb (g/dL)	14.2±1.4	14.0±1.5	0.523
24h post-op Hb (g/dL)	9.5±1.4	10.4±1.5	0.001
Δ Hb (g/dL)a	4.6±1.3	3.7±1.3	0.001
Pre-op RBC mass (mL)	1,950±440	1,877±465	0.203
24h post-op RBC mass (mL)	1,310±350	1,371±363	0.180
Transfused RBC mass (mL)b	89±135	33±96	0.001
Lost RBC mass (mL)	728±252	539±243	0.001
Relative RBC mass loss (%)c	38.7±14.6	29.0±13.1	0.001
24h drainage volume (mL)	401±201	313±151	0.001
24h drainage RBC mass (mL)d	120±63	94±45	0.001
RBCT rate, n (%)	42 (32.6)	15 (12.0)	0.001
RBCT index (units/patient)	0.6±0.9	0.2±0.6	0.001
RBCT units, n (%)			0.001
0	87 (67.4)	110 (88.0)
1	9 (7.0)	4 (3.2)
2	33 (25.6)	10 (8.0)
3	0 (0)	1 (0.8)
Pre-RBCT haemoglobin (g/dL)	7.8±0.4	7.5±0.8	0.115

Values are mean (SD) or number (proportion). Post-op: post-operative; Pre-op: pre-operative; RBC: red blood cell; RBCT: red blood cell transfusion; TXA: topical tranexamic acid; p: p-value.

^aΔ Hb (g/dL) = pre-op haemoglobin (g/dL) – 24 h post-op haemoglobin (g/dL);

^bOne packed RBC unit = 155 mL RBC;

^cExpressed as percentage of pre-op RBC mass;

^dMean haematocrit 30%.

Reduction in blood loss resulted in significantly lower RBCT rates in patients in the TXA group (12 vs 32.6%, respectively; p<0.001; relative risk [RR]=0.37 [95% CI 0.22–0.63]) (Table II), who also received fewer RBC units, when compared to patients in the control group, without differences in pre-transfusion haemoglobin levels (Table II). However, when transfused patients were analysed separately, there were no differences in transfusion index (1.8±0.6 vs 1.8±0.4 RBC units/patient, respectively; p=0.918), despite lower pre-operative haemoglobin levels (12±1 g/dL vs 13.4±1.4 g/dL, respectively; p=0.016) and a trend to a higher percentage of female gender (87 vs 57%, respectively; p=0.059) in the TXA group compared to the control group.

A post-hoc analysis of the efficacy of topical TXA application after THA according to gender and pre-operative haemoglobin level was performed. As depicted in Figure 2, relative RBC mass loss and RBCT rates were higher in females than in males. Topical TXA reduced the relative RBC mass loss in both males (mean difference: 8.5% [95% CI 5.0–12.1%]) and females (mean difference: 13.4% [95% CI 7.3–19.5%]) (Figure 2A), as well as RBCT rates (RR=0.16 [95% CI 0.04–0.65] for males; RR=0.39 [95% CI 0.22–0.69] for females) (Figure 2B).

Figure 2.

Effects of topical tranexamic acid administration on relative RBC mass loss (A) and transfusion rate (B), according to gender and preoperative haemoglobin.

Estimated RBC mass loss at 24 hours after surgery is depicted as percentage of estimated preoperative RBC mass.

Hb: haemoglobin (g/dL); RBC: red blood cells; *p<0.005, tranexamic acid vs control; **p=0.055, tranexamic acid vs control; #p<0.01, female vs male; ##p<0.001, Hb <13 g/dL vs Hb ≥13 g/dL.

Compared to patients presenting with a haemoglobin concentration ≥13 g/dL (n=204; 62% males), those presenting with a pre-operative haemoglobin level <13 g/dL (n=50; 84% females) had a higher RBCT rate (48 vs 14.7%, respectively; RR=3.26 [95% CI 2.10–5.06]; p<0.001), but not higher relative RBC mass losses (37.3 vs 33.1%, respectively; mean difference=4.2% [95% CI −0.39–9.69%]; p=0.073) (Figure 2). However, with respect to controls, TXA reduced relative RBC mass loss in both subgroups of patients (mean difference: 8.6% [95% CI 5.0–12.2%] for patients with haemoglobin ≥13 g/dL; 14.4% [95% CI 4.8–23.9%] for patients with haemoglobin <13 g/dL) (Figure 2A), but a significant reduction in RBCT rates was only observed for the subgroup with a pre-operative haemoglobin ≥13 g/dL (RR: 0.21 [95% CI 0.08–0.53]: p<0.001) and not in the subgroup with a preoperative haemoglobin <13 g/dL (RR: 0.58 [95% CI 0.33–1.01]; p=0.055) (Figure 2B), thus suggesting that a pre-operative haemoglobin concentration <13 g/dL is a risk factor for RBCT, irrespective of topical TXA application.

Discussion

We conducted a pragmatic, open-label randomised study to assess the efficacy and safety of topical TXA application within a blood-saving protocol for primary THA. The results of the study clearly demonstrate that topical TXA was effective at reducing both post-operative RBC mass loss and RBCT rates (Table II). We showed that topical TXA was effective in both females and males (Figure 2). We also showed that the beneficial effect of topical TXA application was restricted to patients with a pre-operative haemoglobin level ≥13 g/dL (Figure 2). Finally, topical TXA application was well tolerated and no clinically apparent thromboembolic complications were witnessed.

THA surgery resulted in significant peri-operative blood loss. Surgical trauma-induced fibrinolysis, which is more pronounced when using a pneumatic tourniquet, also contributes to post-operative bleeding, acute post-operative anaemia and RBCT requirements²⁰. Disadvantages of RBCT have led to the implementation of restrictive transfusion criteria and the development of strategies to minimise RCBT requirements after THA, including the use of anti-fibrinolytic drugs, such as TXA²¹.

Although TXA can be administered orally, intravenously or topically, the most appropriate route of administration and dose, as well as its efficacy and safety, are still a matter of controversy. Several meta-analyses have shown the efficacy of topical and intravenous TXA in reducing blood loss and RBCT requirements in several clinical settings^22,23, and specifically in THA surgery^14,24,25. In a recent, randomised, double-blind, placebo-controlled trial of patients undergoing primary THA, the blood-sparing efficacy of oral TXA was shown to be comparable to that of intravenous and topical TXA¹⁸. In addition, according to pharmacokinetic data from rabbit studies, topical intra-articular application of TXA produced lower peak plasma concentrations but prolonged therapeutic drug levels compared with intravenous TXA²⁶. Another issue of debate is the possibility of serious adverse events, such as deep vein thrombosis or kidney failure, although no evidence for increased risk was reported in published individual studies or meta-analyses which considered TXA as a safe and effective treatment to reduce peri-operative bleeding^14,22–24. Nevertheless, an independent association between peri-operative RBCT and the development of post-operative venous thromboembolism (adjusted odds ratio: 1.7 [95%CI 1.5–2.0]) was recently found among patients undergoing orthopaedic surgery (n=153,320)²⁷. Thus, in our population of patients who received routine pharmacological thrombo-prophylaxis, any potential risk increase conferred by TXA use would have been outweighed by the reduction in RBCT rates.

Peri-operative blood losses in orthopaedic surgery are difficult to measure, and are usually underestimated due to hidden blood loss. In contrast, calculated RBC mass loss is a more accurate parameter as it includes hidden RBC loss from haematomas^2,3. Using this approach, we observed that topical TXA application after THA resulted in reduced absolute and relative RBC mass loss (Table II and Figure 2A). Furthermore, our data showed that topical TXA led to a reduction in both visible and hidden blood loss (Table II), which translated into higher haemoglobin levels at 24 h after surgery and a 63% lower RBCT rate during the hospital stay (RR=0.37 [95% CI 0.22 – 0.63]; p<0.001).

The RBCT rate in the control group was similar to that reported in European benchmark studies^2,3, whereas the RBCT rate in the TXA group was similar to those from a recent meta-analysis of seven studies comparing the use of intravenous TXA (RBCT rate 8%) with topical TXA (RBCT rate 10%)²⁸. In contrast, we found no differences in RBC units per transfused patient (1.8±0.6 vs 1.8±0.4 units/patient, respectively; p=0.918), as 77% of the transfused patients received two units of RBC. This may reflect the persistence of a biased, non-evidence-based thinking that has made two-unit RBCT the norm for decades, and leads to over-transfusion as detected in other clinical settings²⁹. Personalised calculation of RBCT requirements (based on initial haemoglobin or haematocrit and weight) to increase the rate of single-unit transfusions should be performed, as it has been shown to be an effective means of reducing inappropriate RBCT³⁰.

In our study there were more females in the TXA group than in the control group; therefore, data were reanalysed according to gender and pre-operative haemoglobin levels. This post-hoc analysis confirmed that relative RBC mass loss and RBCT rates were higher in females than in males, as previously reported by benchmark studies^2,3, and that these differences remained with the use of topical TXA (Figure 2A,B). Topical TXA reduced RBC loss in all patients, irrespectively of pre-operative haemoglobin levels (Figure 2A), but this only translated into a significant reduction of RBCT rate in those with haemoglobin ≥13 g/dL (Figure 2B).

Anaemia is defined by the World Health Organisation (WHO) as a haemoglobin concentration <13 g/dL for men and <12 g/dL for non-pregnant women³¹. However, the WHO definition of anaemia may not be reliable for the classification of women undergoing surgical procedures with expected moderate-to-high blood loss, such as THA, and a pre-operative haemoglobin ≥13 g/dL would be desirable^32,33. In our study, females were more likely than men to present with a pre-operative haemoglobin <13 g/dL (38.5% vs 6.7%, respectively; p<0.001). This is in agreement with previously published data on larger populations of patients undergoing lower limb arthroplasty (n=1,286), and suggests a benefit from pre-operative optimisation of haemoglobin concentration³⁴.

However, detection and early treatment of pre-operative anaemia are logistical challenges and, as a consequence, some patients may undergo surgery without their anaemia having been addressed^32,35. As iron deficiency is the most common cause of anaemia in this population of patients and recombinant human erythropoietin is licensed for use in elective orthopaedic surgery in Europe, our current blood-saving protocol already considers the peri-operative administration of intravenous iron sucrose (3 × 200 mg) to all patients, plus a single pre-operative dose of recombinant human erythropoietin (40,000 IU) upon admission in those with haemoglobin <13 g/dL, regardless of gender. However, this protocol seemed insufficient in THA¹⁹. To achieve greater reductions in the incidence of RBCT, we are now considering earlier optimisation of pre-operative haemoglobin, starting 3–4 weeks prior to surgery, as recommended by recent guidelines^19,32,36. An additional focus on the early detection and treatment of post-operative iron deficiency and anaemia, as complementary measures within the concept of patient blood management, will allow the attending physician to target patients with significant RBC mass loss during surgery who may require specific attention post-operatively or after discharge^37–39.

This study has some limitations. First, it was a single-centre study and, although this ensured uniform patient care in both groups, including aggressive peri-operative haemoglobin management, the applicability of the study’s findings to other centres might be limited. Secondly, randomisation by medical record number may be not a sufficiently robust method to prevent selection bias. This might explain the lack of sex balance in the groups and have introduced a bias in the assessment of outcome variables. However, rather than estimated volume of blood loss we calculated RBC mass loss, which is based on peri-operative haematocrit change and patient’s circulating blood volume and, therefore, very unlikely to be influenced by the observer. RBCT indications may be subjective; however, there were neither transfusion protocol violations nor differences in pre-RBCT haemoglobin (Table II). In addition, most transfused patients in both groups received two units of RBC, even though this may represent suboptimal practice. Thirdly, RBC loss was calculated on post-operative day 1, rather than on post-operative day 4 (nadir haemoglobin)^2,3, which may have underestimated total blood loss in both groups; however, most blood loss in THA occurs during surgery and the first post-operative day. Recent guidelines recommend haemoglobin monitoring for the first 3–4 days after major surgery³⁹, but this was not standard practice at our centre. Therefore, for this pragmatic trial, we used pre-operative and 24 h post-operative haemoglobin concentrations, which were routinely assessed in all patients. Lastly, although no clinically apparent thromboembolic complications were observed, neither this trial nor other published studies are large enough to provide the statistical power to detect differences in the rates of post-operative complications with a low incidence, such as thromboembolic events⁴⁰.

Conclusions

Despite the above-mentioned limitations, it seems that our data add to the growing body of evidence on the efficacy of topical TXA application after THA to reduce blood loss and RBCT rates. Nevertheless, although more research is needed regarding the dose and method of application of TXA, adherence to a one-unit transfusion policy and pre-operative haemoglobin optimisation would further improve the efficacy of topical TXA.