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Tranexamic Acid Compared with Placebo for Reducing Total Blood Loss in Hip Replacement Surgery: A Randomized Clinical Trial

Barrachina, Borja MD; Lopez-Picado, Amanda Pharm; Remon, Maria MD; Fondarella, Ana MD; Iriarte, Ibai MD; Bastida, Rebeca MD; Rodríguez-Gascón, Alicia MD; Achaerandio, Maria Aranzazu MD; Iturricastillo, Maria Carmen MD; Aizpuru, Felipe MD; Valero, Cesar Augusto MD; Tobalina, Ricardo MD; Hernanz, Roberto Pharm

doi: 10.1213/ANE.0000000000001159
Ambulatory Anesthesiology and Perioperative Management: Research Report
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BACKGROUND: Tranexamic acid (TXA) reduces bleeding in patients undergoing hip replacement surgery, but optimal doses and timing have yet to be established. Our primary objective in this study was to assess total blood loss 48 hours after surgery with different regimens.

METHODS: This was a multicenter, parallel-group, randomized, placebo-controlled clinical trial that included all ASA physical status I to III patients undergoing unilateral total hip replacement surgery who met the inclusion criteria. Patients were randomly allocated to 1 of 3 groups: a single-dose group (15 mg/kg TXA before the start of surgery and saline 3 hours later after the start of surgery), a 2-dose group (10 m/kg TXA before and 10 mg/kg of TXA 3 hours after the start of surgery), and a control group (saline before and 3 hours after the start of surgery). Total blood loss was calculated using a formula considering hematocrit values and blood transfusions received.

RESULTS: We included 108 patients in the study. Total blood loss volumes up to day 2 were 1377 ± 689, 1308 ± 641, and 2215 ± 1136 mL in the single-dose, 2-dose and control groups, respectively (P < 0.001 between the placebo and the experimental groups). Blood transfusions were given to 22.9% of patients (n = 8) in the single-dose group, 11.1% (n = 4) in the 2-dose group, and 37.8% (n = 14) in the control group (P = 0.028).

CONCLUSIONS: A single preoperative dose of TXA or 2 infusions of a lower dose, preoperatively and then after 3 hours after the start of surgery, resulted in lower blood loss during the first 2 days after surgery and less need for blood transfusion, with good levels of safety.

From the *Department of Anaesthesia and Perioperative Care, Araba University Hospital, Vitoria-Gasteiz, Spain; Araba Research Unit, Araba University Hospital, Vitoria-Gasteiz, Spain; Department of Anaesthesia and Perioperative Care, Garcia Orcoyen Hospital, Estella, Spain; §Department of Radiology, Araba University Hospital, Vitoria-Gasteiz, Spain; Pharmacy and Pharmaceutical Technology, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain; Central Laboratory, Araba University Hospital, Vitoria-Gasteiz, Spain; #Department of Orthopaedic Surgery and Trauma, Araba University Hospital, Vitoria-Gasteiz, Spain; and **Pharmacy Service, Araba University Hospital, Vitoria-Gasteiz, Spain.

Accepted for publication December 7, 2015.

Funding: None.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Borja Barrachina, MD, Servicio de Anestesiología y Reanimación, Hospital Universitario de Araba- Sede Txagorritxu, c/ Jose Atxotegui s/n, 01009 Vitoria-Gasteiz, Alava, Spain. Address e-mail to borjabarra@gmail.com.

With increases in life expectancy, total hip replacement (THR) surgery has become one of the most common orthopedic procedures,1,2 and it is associated with significant blood loss during and after surgery.3–5 Despite considerable advances in the safety of blood transfusions, they are still not risk free, being associated with transmission infections, immunologic reactions, and other complications.6,7 Moreover, blood is an expensive resource, and the supply may be insufficient. These factors create a need to find ways to minimize bleeding and its consequences.

Many strategies have been proposed to minimize the risk of bleeding and the need for perioperative homologous blood transfusions.8 Some of these techniques take time to be effective or require expensive devices,9,10 and they do not always ensure good blood quality.11 Conversely, many agents have been proposed for reducing the risk of perioperative transfusion, administered preoperatively,12 perioperatively,13 or in the event of massive hemorrhage,14,15 with mixed results.16 Tranexamic acid (TXA) is an antifibrinolytic agent that is widely used for reducing blood loss in THR surgery. It interferes with the process of fibrinolysis17 reducing bleeding and the need for transfusion.18 The efficacy of TXA in reducing blood loss and its good safety profile have been demonstrated in many types of surgery.19,20 Regarding THR, although results have also been good21,22 with various timings and doses of TXA,23,24 the best treatment regimen to maximize efficacy and minimize adverse effects has yet to be established. In this context, there was a clear need for further research.25 Hence, we conceived this study to investigate the efficacy of TXA in reducing total blood loss in THR surgery, with different treatment regimens and doses, interpreting the results as a function of measures of fibrinolysis.

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METHODS

We conducted a randomized, double-blind, parallel-group, placebo-controlled trial in 2 hospitals in which 165 hip replacement operations (unilateral, bicompartmental, primary, uncemented, posterolateral, or anterolateral) were performed for arthrosis (March 2011 to December 2012). The study was approved by the Clinical Research Ethics Committees of the Basque Country and Navarre as well as by the Spanish Agency for Medicines and Health Products, and this was registered before patient enrollment in EudraCT (EudraCT number: 2010-021497-11) and in clinicaltrials.gov (register number: NCT01199627). Patients who agreed to be in the study and met the selection criteria gave written informed consent for study participation.

Patients were recruited by the anesthesia team. All ASA physical status I to III patients older than 18 years with no known allergy to TXA were invited to participate. We excluded patients who met 1 or more of the following criteria: pregnancy or breastfeeding, severe vascular ischemia, history of venous thrombosis, pulmonary embolism or diseases causing embolism, known coagulopathies, long-term treatment with acetylsalicylic acid or nonsteroidal anti-inflammatory drugs not discontinued before surgery, a hemoglobin (Hb) concentration <10 mg/dL, moderate renal impairment, liver cirrhosis, or any contraindications to prophylaxis with enoxaparin.

Patients were randomly allocated to 1 of 3 groups using a computer-generated random number list held in the Araba Research Unit, hidden from participating clinicians. To keep participating clinicians blind to patient allocation, study medication was prepared by the pharmacies of the participating hospitals in compliance with current regulations. At the time of surgery, the pharmacy delivered 100-mL bags labeled with patient codes; depending on their allocation, bags contained only saline or saline with 1 of 2 doses of TXA but given that TXA solution is colorless, and the different bags were indistinguishable. In the 2 hospitals groups, surgery was performed following the same protocol (Appendix 1) and using the same blood-saving strategies (Appendix 2).

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Intervention

Patients in all 3 groups were administered 2 infusions.

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Single-Dose TXA Group

Patients assigned to single-dose TXA group (SDG) received an IV infusion of 15 mg/kg TXA (Amchafibrin®, Rottapharm, Barcelona, Spain) in 100 mL of 0.9% saline over a 10-minute period after the institution of regional anesthesia and before the start of surgery. Three hours after the first infusion, they received a second infusion over 10 minutes but this time with 100 mL of 0.9% saline alone.

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Two-Dose TXA Group

Patients assigned to this 2-dose TXA group (TDG) received 10 mg/kg TXA (Amchafibrin®, Rottapharm, Barcelona, Spain). As in the SDG, this was diluted in 100 mL of 0.9% saline and infused IV (intravenous) over 10 minutes, after instituting regional anesthesia and before starting surgery, and 3 hours later after the start of surgery, they received a second infusion at the same dose and rate as the first.

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Control Group

Patients assigned to control group (CG) received an IV infusion of 100 mL of 0.9% saline over a 10-minute period after instituting regional anesthesia and before starting surgery. Three hours later, they received a further of 100 mL of 0.9% saline over 10 minutes.

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Transfusion Trigger

Before starting the surgery, transfusion trigger levels were set at 8.5 g/dL of Hb under normovolemic conditions and at 9 g/dL in cases of moderate cardiac or respiratory diseases or symptoms of acute anemia (angina, hypotension, dyspnea).

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Variables

Blood Loss

The primary outcome measure, total blood loss up to day 2 after surgery, was estimated using a formula proposed by other authors26 (Appendix 3). We estimate hematocrit (Hct) values before surgery and at the time of assessment (48 hours after surgery) and any blood transfusions given in this period. The same formula was used to determine secondary outcome measures associated with bleeding, namely, blood loss up to 1 and 6 hours after the start of surgery.

In addition, intraoperative blood loss (in the operating room) was estimated by measuring the volume of blood collected in suction canisters and the weight of blood-soaked materials (gauzes, pads, etc.) and subtracting the dry weight of these materials and the volume of saline used for cleaning the surgical site. Postoperative blood loss was estimated by quantifying the volume collected in drains up to 2, 6, 24, and 48 hours after the start of surgery. Objectively measured perioperative blood loss was estimated by summing intraoperative blood loss and postoperative blood loss up to 48 hours. All transfusions were recorded (time of administration and the number of units). We considered autologous and homologous transfusions separately and the total values.

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Blood Tests

Complete blood counts were performed using samples taken from the patient’s arm before surgery; at 1, 6, and 24 hours; at 2, 4, and 6 days after the start of surgery, and immediately after each transfusion. In addition, plasmin-antiplasmin complex (PAP), plasminogen activator inhibitor type 1 (PAI-1), and D-dimer levels were measured with an enzyme-linked immunosorbent assay before surgery and 1 and 6 hours after the start of surgery. D-Dimer levels were tested in all patients (VIDAS D-Dimer, BioMerieux, Marcy J’Etoile, France), PAP and PAI-1 levels only in the last 8 patients recruited in each group (Human ELISA kits, Assaypro, St. Charles, MO).

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Complications

Thrombosis

All patients underwent Doppler ultrasound on both legs by an experienced radiologist 3 and 21 days after surgery. During admission, patients were examined each day by doctors not participating in the study to detect any of the following signs or symptoms in the calf: pain on palpation, hardening or swelling, increased circumference, or Homans sign. If 2 or more symptoms were present, we performed an additional Doppler ultrasound examination, maintaining the aforementioned scheduled scans.

We recorded all complications associated with the procedure during admission and up to 3 months after surgery by reviewing the electronic medical records. All detected complications were treated following clinical practice guidelines.

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Surgical Procedure

Surgery was performed by an experienced surgical team following a common protocol to standardize the procedures for all patients independently of the group and hospital assigned (Appendix 1). Surgery was performed under subarachnoid spinal block (12.5–13.5 mg isobaric bupivacaine 0.5% + 15 µg fentanyl). During surgery, lost blood was replaced by hydroxyethyl starch 130/0.4 (Voluven®, Fresenius-Kabi, Bod-Homburg, Germany) at a 1:1 ratio and lactated Ringer’s solution at a 3:1 ratio provided that the Hb level did not reach the transfusion trigger. Conversely, if the Hb did decrease to the trigger level, we transfused 1 unit of homologous red blood cells in saline. Hb levels were tested again and transfusions repeated until levels increased to above the trigger.

All patients were treated with enoxaparin (40 mg/24 h if they had a body weight <80 kg or 60 mg/24 h if they had a body weight >80 kg) from the day before surgery and until day 40 after surgery. For antibiotic prophylaxis, we gave 2 g IV cefazolin before surgery and three 1-g doses cefazolin/8 h after surgery. Patients who were allergic to cefazolin were given vancomycin, a 1.5 g dose 1.5 hours before surgery and 1 g/12 h after surgery. During hospitalization, analgesia was provided in both hospitals following the same protocol that included paracetamol and metamizole, as well as rescue boluses of subcutaneous morphine.

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Statistical Analysis

Statistical analysis was performed using IBM SPPS Statistics version 22 (International Business Machines Corp., NY). Continuous variables were described using means and SDs (standard deviation) and qualitative variables using frequencies and percentages.

The primary outcome, total blood loss up to day 2 after surgery, was assessed using parametric analysis of variance both with and without the Bonferroni correction for multiple comparisons. We assessed the impact of potential confounding variables (Hb concentrations, preoperative international normalized ratio, and surgical time) by multivariate linear regression analysis. We also used this analysis to investigate differences between groups in blood volume in drains and Hb, Hct, D-dimer, PAP, and PAI-1 levels.

The secondary outcome measures including rates of thrombosis and complications at 3 and 21 days after surgery and transfusions (total, autologous and homologous) were assessed by logistic regression analysis. Further, the effect of confounding variables (Hb concentrations and blood volume in drains at 6 hours after surgery) on rates of transfusions was explored by multivariate logistic regression.

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Sample Size Calculation

To have a power of 90% to detect a difference of 200 mL among groups with an α risk of 0.05, assuming a high dispersion of data (μ = σ), we estimated that we required 32 patients per group. Assuming a loss of 10% during follow-up, we needed to recruit 108 patients (36 per group). Given that this trial had 3 arms and hence 3 hypotheses, to maintain an overall level of significance of 0.05, we used the Bonferroni correction, and this yields a level of significance of 0.017 for each arm.

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RESULTS

Table 1

Table 1

Figure 1

Figure 1

During the study period, 165 hip replacement operations were performed in the 2 participating hospitals. Having excluded patients not meeting the selection criteria, 113 consecutive patients were recruited for the study. After randomization, 2 patients were excluded (Fig. 1). In addition, 2 patients, 1 in the TDG (ASA physical status I) and 1 in the CG (ASA physical status II), were excluded after administration of the first dose of study medication given the need to convert to general anesthesia because of a failure with the regional technique. Another patient in the CG (ASA physical status III) was withdrawn because of deviation from the protocol (he was given a dose of TXA in the postoperative period). Patients’ main characteristics are summarized in Table 1.

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Blood Loss

The main study variables are presented in Table 2 and Figure 2. By using the formula of Camarasa et al.,26 total blood loss up to day 2 was estimated to be 1377 ± 689 mL in the SDG (single dose of 15 mg/kg TXA), 1308 ± 641 mL in the TDG (2 doses of 10 mg/kg TXA), and 2215 ± 1136 mL in the CG. Differences in blood loss up to 2 days between the placebo and the 2 experimental groups were significant (P < 0.001), even after adjusting for Hb concentration and blood volume in the drains 6 hours after surgery (1377 ± 689 mL in the SDG, 1341 ± 619 mL in the TDG, and 2310 ± 1152 mL in the CG; P = 0.010). At 1 hour after surgery, the volumes were 847 ± 585, 850 ± 446, and 838 ± 391 mL for the SDG, TDG, and CG, respectively, with no significant differences (P = 0.994; 95% confidence interval, 751–941). Similarly, it was estimated that 1024 ± 378, 1014 ± 440, and 1078 ± 494 mL of blood had been lost by 6 hours after surgery in the SDG, TDG, and CG, respectively (P = 0.229). We found no significant differences in measured intraoperative (P = 0.536) or perioperative (P = 0.176) blood loss.

Table 2

Table 2

Figure 2

Figure 2

Figure 3

Figure 3

Regarding drains (Fig. 3), we observed differences in the volumes of blood collected by 2, 6, 24, and 48 hours after surgery (Table 2), with differences in all cases between the CG and the 2 experimental groups (SDG and TDG). In contrast, we did not find differences between the groups in blood loss from 6 to 48 hours after surgery (P = 0.916).

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Hemoglobin, Hematocrit, and D-Dimer Levels

The levels of Hb (Table 2) did not differ significantly among the 3 groups 1 hour after surgery (P = 0.587). However, there were differences at 6 (P = 0.018) and 24 (P < 0.001) hours and 2 (P < 0.001), 4 (P = 0.001), and 6 (P = 0.012) days. Although D-dimer levels (Table 2) were similar across groups preoperatively (P = 0.451), there were significant differences in this variable at 1 and 6 hours after surgery (P < 0.001 in both cases).

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Transfusions

Table 3

Table 3

The percentages of patients receiving a blood transfusion were (Table 3) as follows: 22.9% of patients in the SDG, 11.1% in the TDG, and 37.8% in the CG (P = 0.028). Notably, the differences remained significant after adjusting for Hb concentration, preoperative international normalized ratio, and surgical time (22.9% of patients in the SDG, 11.1% in the TDG, and 37.8% in the CG; P = 0.027). Overall, 23 patients (21.3%) received homologous blood, with a mean of 1.9 ± 0.9 units per patient.

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Complications

In the ultrasound scan 3 days after surgery, thrombosis was detected in 4 patients (3.8%; Table 4), one of whom (in the TDG) had a pulmonary thromboembolism with a good outcome. In clinical examinations, there were no findings compatible with thrombosis. In the ultrasound scan 3 weeks after surgery, thrombosis was detected in 3 patients (3.2%).

Table 4

Table 4

As for infectious complications during admission, 1 patient in the SDG developed acute gastroenteritis and 1 patient in the TDG had pulmonary edema (Table 4). Three months after surgery, no patients had complications associated with the surgery. Concerning hospitalization, the study patients were admitted for a mean of 8.3 ± 2.3 days. Lengths of stay were 8.4 ± 2.3, 8.4 ± 2.6, and 8.0 ± 2.0 days in the SDG, TDG, and CG, respectively (P = 0.689).

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PAI-1 and PAP

Table 5

Table 5

PAI-1 (Table 5) and PAP levels were measured in a sample of 24 patients, but no significant differences were detected either at baseline or after surgery (1 and 6 hours).

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DISCUSSION

This study shows that TXA administered as a single dose (preoperatively) or in 2 doses (1 preoperatively and 1 postoperatively) decreases bleeding up to day 2 after surgery in patients undergoing THR. The lower level of bleeding was apparent in both the estimated blood loss based on patient Hct levels and the volume of blood collected postoperatively in drains. Conversely, differences in observed perioperative blood loss did not reach statistical significance. It is likely that this last method tends to underestimate real blood loss27 and does not consider the blood accumulated in soft tissues. Therefore, it is difficult to compare results between studies, given heterogeneity in the methods used for quantifying blood loss.25

The findings of this study are compatible with those of other studies that have suggested that TXA is more effective when administered before the beginning of surgery than after surgery.22–24 However, we did not find significant differences between a single preoperative dose and 2 lower doses (1 before and 1 after surgery).

Neither measured intraoperative blood loss nor Hb concentrations at 1 hour after starting surgery (approximately the usual time of completion of the procedure) differed between groups, and this suggests that the differences observed were due to significantly less postoperative bleeding in the groups treated with TXA, as confirmed by the volume of blood collected in the drains. In this sense, our results differ from those of studies in which TXA reduced intraoperative blood loss22,28 although this has not been found in all previous studies.29 It seems plausible that differences between study groups would not be observed during surgery in tissue-type plasminogen activator levels, because of the steps taken by the trauma surgeon to achieve hemostasis (irrigation of the surgical field, electrocautery, etc.), and that it is only in the immediate postoperative period that such differences become discernible, when the local accumulation of tissue-type plasminogen activator in the wound leads to an increase in fibrinolytic activity.

There is consensus on the idea that bleeding as measured from blood-soaked materials and surgical drains underestimates the volume lost because it does not consider blood retained in tissues. Given this, numerous authors have proposed formulae for obtaining estimates that are more objective. The formulae of Nadler et al.30 and Gross31 are among the most widely used. However, Gross’s formula31 does not consider transfusions, and Nadler et al.’s30 formula does not distinguish between autologous and homologous transfusions. The formula proposed by Camarasa et al.26 that we used in this study improves on earlier formulae in that it not only considers transfusions and their type but also considers sex and body weight, thereby providing a more realistic estimate of a patient’s blood volume.

However, the estimates of blood loss during the first hours after surgery, based on the formula of Camarasa et al.,26 do not contribute to the interpretation of the intensity of postoperative bleeding, because these early estimates concern situations in which patients may not be normovolemic. Specifically, the formula cannot be used as a basis for drawing conclusions on the pattern of blood loss until 2 days after surgery, when it can be considered that patients have returned to their baseline normovolemic status.

TXA was introduced earlier in orthopedic surgery for total knee replacement. It has been used since the 1990s, probably in recognition of the fibrinolytic activity that is well known to be generated during the ischemia time, because of the pressure of the pneumatic tourniquet on the muscle during surgery. However, in the 2000s, clinical trials with TXA in hip replacement surgery started to yield good results, although with great variations in the dose and how it was administered.23,24,32

It is possible that the second dose of TXA did not show greater efficacy in reducing bleeding because the body dampens the fibrinolytic process beyond 6 hours after surgery, and this tends to be replaced by an antifibrinolytic or even prothrombotic status, in a delicate hemostatic balance.33 In relation to this, our D-dimer results indicated clearly smaller increases in fibrinolytic status in the TXA-treated groups than the placebo group. However, we did not find significant differences between the 2 treatment regimens, suggesting that adding the second dose of TXA does not provide greater efficacy than a single higher dose. Moreover, we did not find differences between the treatment groups in the estimated blood loss based on volumes collected in drains, strengthening the idea that the second dose of TXA does not improve clinical outcomes. However, given that the study sample size was not selected to test that hypothesis, it would be interesting to conduct additional clinical trials to assess which of the 2 regimens is the most effective.

Measurements of PAP and PAI-1 levels (in a subset of patients) have not contributed to the interpretation of our findings, possibly because of factors responsible for the local increase in fibrinolysis in the operated leg being diluted by venous blood coming from other types of tissue elsewhere, as well as pulmonary filtration and liver metabolism. In contrast, the fibrinolytic status of patients was reflected in levels of D-dimer, because this molecule stays in the systemic circulation before being metabolized.31

Considering blood transfusions, we found significant differences between groups, suggesting that less blood loss decreased the need for blood transfusion, despite transfusion trigger levels being less restrictive than those used in some other studies.34 Far from reducing the validity of the study, the transfusion trigger levels we used were selected to reflect daily clinical practice in our hospitals and also enable our results to be extrapolated to other hospital settings. Similarly, some authors have reported that reductions in bleeding have led to reductions in the need for blood transfusion,35 although this has not been observed in all cases.28

Our study population had body mass index values similar to those found in some research,36 although markedly lower than those in other studies.4,37 Although lower weight could contribute to less blood loss, our study shows the efficacy of TXA even under these conditions. The fact that the results support the use of TXA regardless of body mass index makes us believe that the findings can be extrapolated to other populations.

In recent years, TXA has been advocated for many types of surgical procedures19,38 and has a good safety profile.39 Regarding safety, although our study was designed to explore bleeding, we have not found differences in the incidence of perioperative thrombosis. A dose of 15 mg/kg has appeared to be safe when used in various other clinical situations. Although higher doses may be associated with a greater risk of thrombosis40 and convulsions,41 several studies with much higher doses have not observed an increase in the rate of complications.42,43

One of the limitations of our study was the limited measurement of D-dimer levels (and PAP and PAI-1 levels); the fibrinolytic status of patients would be better characterized with serial measurements beyond the first 6 hours, at least throughout the first day after surgery. In relation to future work, we sought to test the treatment regimens currently most widely used in clinical practice, but it would be interesting to conduct pharmacokinetic analysis to optimize the dose.

To conclude, the use of TXA in THR surgery reduces postoperative bleeding with a good safety profile, both as a single 15 mg/kg dose before surgery and as 2 spaced 10 mg/kg doses; no differences were found between these regimens. The smaller blood loss seemed to be associated with a decreased need for transfusions in both treatment groups (TXA) than the CG.

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APPENDIX 1

Surgical Protocol

Patient in lateral decubitus position, with the contralateral leg flexed at knee and hip, with small cushions supporting it. A pillow placed between thighs and fixed to the table with a bandage; pelvic and lumbar support.

Posterior lateral or lateral incision. Articular capsule opened. Posterior dislocation of the femoral head; soft tissue removed from the neck and trochanter with Rongeur forceps and scalpel. Neck cut with a saw, starting 1 cm above the lesser trochanter and finishing close to the upper part of the greater trochanter. Two Hoffman retractors inserted to expose the acetabulum, which then has soft tissue removed using a surgical spoon, Rongeur forceps, or scalpels, as needed, and is reamed until previously measured size achieved, exposing the subchondral bone and this being covered in the desired position in terms of inclination and anteversion.

Insertion of the acetabular cup impacted. Polar screw and implantation of the polyethylene insert also impacted.

Move the retractors to expose the femoral surgical incision; create access manually with a gouge after the diaphysis; widening the access with straight reamers and later with anatomical reamers, always keeping to the outer part of the diaphysis to avoid genu varum; continuing until previously measured size achieved. Insert a femoral stem of the same size as the reamer.

Trial femoral head placed and reduced. Stability and mobility checked. Dislocation and trial component replaced by final ball, as selected in the test.

Closure layer by layer leaving 2 Redon drains in the line of the surgical incision, 1 deeper distally and 1 more superficial proximally.

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APPENDIX 2

Program for Blood Saving in Orthopedic Surgery

On the basis of preoperative hemoglobin (Hb) levels:

  1. Hb < 10 g/dL: Postpone surgery. Refer patient to hematology specialist for anemia workup.
  2. Hb > 15 g/dL: Immediately operable. Request cross-matching, given potential need for homologous blood.
  3. Hb = 10 to 13 g/dL: Complete form for blood bank to request erythropoietin treatment. Request cross-matching of homologous blood (3 units).
  4. Hb = 13 to 15 g/dL: Complete form for blood bank to request extraction of 2 units of autologous blood and cross-matching of homologous blood (1 unit).
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After Surgery

IV iron the day of surgery and day 2 and 4 after surgery, if the patient’s Hb levels are >11 g/dL and transfusion has not been performed.

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Appendix 3

Formulae Used to Calculate Total Blood Loss

Figure

Figure

Adapted from the study by Camarasa et al.26 Formulae used to calculate total blood loss. TBL = total blood loss; TRCL = total red cell loss; Hi = hematocrit the night before surgery; Hf = hematocrit fifth day after surgery; ARCL = accepted red cell loss; Vth = estimated volemia (in illiliters); VTRC = volume of transfused red blood cells.

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DISCLOSURES

Name: Borja Barrachina, MD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Borja Barrachina has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Amanda Lopez, Pharm.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Amanda Lopez has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Maria Remon, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Maria Remon has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Ana Fondarella, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Ana Fondarella has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Ibai Iriarte, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Ibai Iriarte has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Rebeca Bastida, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Rebeca Bastida has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Alicia Rodriguez, MD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Alicia Rodriguez has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Maria Aranzazu Achaerandio, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Maria Aranzazu Achaerandio has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Maria Carmen Iturricastillo, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Maria Carmen Iturricastillo has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Felipe Aizpuru, MD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Felipe Aizpuru has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Cesar Augusto Valero, MD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Cesar Augusto Valero has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Ricardo Tobalina, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Ricardo Tobalina has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Roberto Hernanz, Pharm.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Roberto Hernanz has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

This manuscript was handled by: Tong J. Gan, MD, MHS, FRCA.

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