Topical vs Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A Double-Blind, Randomized Controlled Trial

Topical vs Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A Double-Blind, Randomized Controlled Trial

Accepted Manuscript Topical Versus Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A Double-Blind, Randomized Controlled Trial W. Trevo...

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Accepted Manuscript Topical Versus Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A Double-Blind, Randomized Controlled Trial W. Trevor North, M.D., Nima Mehran, M.D., Jason Davis, M.D., Craig Silverton, D.O., Robb Weir, M.D., Michael W. Laker, M.D. PII:

S0883-5403(15)00982-1

DOI:

10.1016/j.arth.2015.11.003

Reference:

YARTH 54796

To appear in:

The Journal of Arthroplasty

Received Date: 12 February 2015 Revised Date:

10 September 2015

Accepted Date: 2 November 2015

Please cite this article as: North WT, Mehran N, Davis J, Silverton C, Weir R, Laker MW, Topical Versus Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A Double-Blind, Randomized Controlled Trial, The Journal of Arthroplasty (2015), doi: 10.1016/j.arth.2015.11.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Title: Topical Versus Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A Double-Blind, Randomized Controlled Trial

Corresponding Author:

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W. Trevor North M.D. [email protected] Phone: 248 904 8743

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Fax: 313 916 0475 Henry Ford Hospital

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2799 West Grand Blvd Detroit, MI 48202

(All authors share the above address, affiliation and fax number) Nima Mehran M.D.

Craig Silverton D.O. Robb Weir M.D.

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Michael W. Laker M.D.

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Jason Davis M.D.

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Topical Versus Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty: A

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Double-Blind, Randomized Controlled Trial

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Abstract

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Abstract

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Background: Tranexamic acid (TXA) reduces perioperative bloodloss in total hip arthroplasty

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(THA). Methods: In our randomized control trial, 139 patients were enrolled and received 2g of

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either topical or IV TXA. Pre and postoperative protocols were standardized. Results:

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Calculated blood and Hgb loss were lower in the IV group (1195.0±485.9 mL, 1442.7 ± 562.7

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mL)(p=0.006), (160.3(g) ±63.8, 188.4(g) ± 68.5)(p=0.014). There was a trend toward

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significance in transfusion reduction (11% (IV) vs.18% (Topical))(p=0.3). Both groups effectively

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reduced the transfusion rate. There was significant financial incentive for the use of TXA in THA

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with a savings of $314 per patient. Conclusions: IV and topical TXA are effective tools to reduce

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blood loss and transfusion costs in THA and we recommend the IV form for ease of use.

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Keywords: Tranexamic acid, Total hip arthroplasty, Perioperative blood conservation

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Introduction Perioperative blood loss and subsequent allogenic red blood cell transfusions are common in orthopaedic surgery and present a potential for adverse outcome. Postoperative

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anemia often delays functional recovery and prolongs patient length-of-stay following total joint

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arthroplasty (TJA), subjecting patients to iatrogenic complications and hospitals to unwanted

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costs [1, 2]. Over the last several decades, blood transfusions have demonstrated decreased

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risks and improved safety, especially with the introduction of leukocyte reduction and how it

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relates to perioperative infection in this population [3, 4]. Although direct consequences of blood

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transfusion have decreased [5-7], we continue to transfuse to help prevent multifactorial

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complications such as delayed rehabilitation, falls and cardiac manifestations to name a few.

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For these reasons, orthopaedic surgeons seek to minimize blood loss associated with TJA. In

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addition to surgical and anesthetic methods, some surgeons are utilizing pharmacologic

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adjuncts like tranexamic acid (TXA).

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TXA has been successful at reducing blood loss and lowering transfusion rates in several surgical procedures including total hip arthroplasty (THA) [8]. Its antifibrinolytic

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properties arise from its chemical structure as a synthetic lysine analogue. In normal fibrinolysis,

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tissue plasminogen activator binds to plasminogen, and together they engage fibrin resulting in

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fibrinolysis. TXA competitively binds to plasminogen at the fibrin binding site resulting in a

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decreased rate of fibrinolysis and a theoretical reduction in blood loss.

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The number of primary THA’s continues to rise annually, with a projected increase to

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572,000 in the United States by the year 2030 [9]. Reduction in transfusion rate and

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perioperative blood loss can improve patient safety and outcomes. The use of TXA in the adult

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reconstructive literature is becoming more prevalent. Several studies on total knee arthroplasty

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have identified that topical and intravenous (IV) administration are both useful modes of

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administration, with IV being superior with respect to blood loss and postoperative transfusion

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requirement [10-13]. The THA literature has focused on IV or topical administration versus

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placebo without head-to-head comparison. It is our intent to address this gap with a comparative

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analysis of topical and IV TXA in primary unilateral uncemented THA.

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Materials and Methods

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We performed a prospective, double-blinded, randomized control trial recruiting patients from two centers within a single institution. All patients scheduled for primary, unilateral THA

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were flagged for study inclusion. The patients were then sequentially excluded from participating

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if any criteria listed in Table I were met. Exclusion criteria were established through

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recommendation from a panel of clinicians, including orthopaedists and anesthesiologists within

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the institution. A power analysis was conducted based on available data for comparison

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between topical and IV administration of TXA in primary THA. Using power of 0.8 and a p-value

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of 0.05, the target enrollment was 70 patients per arm of the study. Our primary outcomes

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included assessment of blood and hemoglobin loss as well as transfusion rates within each

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group. Secondary outcomes included a transfusion cost analysis relative to historic controls and

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an assessment of thromboembolic events. Our historic transfusion rate for patients undergoing

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primary uncemented THA was 34% from 2009-2011.

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The randomization algorithm was created by a blinded biostatistician and patients were

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allocated in blocks of four by a blinded research pharmacist. The randomization was not broken

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until study completion; all patients underwent intent to treat analysis and all data had been

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accounted for in a restricted access database. Surgeries were performed at two hospitals by

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one of five fellowship trained adult reconstructive surgeons.

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Perioperative Protocols

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Once informed consent was obtained, the patient was randomized to receive 2.0 g of

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either topical or intravenous (IV) TXA in 100ml of 0.9% normal saline solution. Two solutions

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labeled “IV” and “Topical” accompanied the patient to the operating room (One solution

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contained the 2.0 g of TXA and the other contained saline placebo). Pragmatic dosing was

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decided on for ease of administration and demonstrated effectiveness from previous studies

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[10, 14-16]. The IV solution was administered by anesthesia in two 50ml doses, each over 20

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minutes using a pump to ensure the correct volume was administered. One administration was

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started 10 minutes prior to incision, and the second during the fascial closure. The topical

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solution was applied to the wound by the surgical team following component placement and

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allowed to sit undisturbed for five minutes at which point it was removed by suction. No drains

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were used on study patients. The timing and duration of topical administration emulates several

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studies in the literature [10, 14-16]. By study design, each patient received a topical and an IV

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administration of study solution, only one of which included TXA.

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Postoperative venous thromboembolic (VTE) chemoprophylaxis was not standardized in

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an attempt to improve generalizability, but abided by the American Academy of Orthopaedic

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Surgeons (AAOS) clinical practice guidelines [17]. Patients received either: Lovenox 40mg daily

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for 21 days, Rivaroxaban 10mg daily for 35 days, or aspirin 325mg bid for 21 days. All

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chemoprophylaxis was initiated on the morning of postoperative day one. All patients received

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mechanical thromboprophylaxis with early mobilization and pneumatic leg compression devices.

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Patients had a standardized preoperative and postoperative employment of a pain management

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ladder.

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Hemoglobin levels were obtained preoperatively and daily thereafter until postoperative

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day three. All patients stayed three or more days. A standardized postoperative transfusion

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protocol was used. Patients were transfused at Hgb < 7 g/dL in all cases and in cases of

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symptomatic anemia when Hgb < 8 g/dL. We chose the parameters to align with current 4

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practice within the institution to avoid confusion and variability in the after care of study

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participants. Calculated values of Hemoglobin and blood loss were resulted according to a

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previously validated formula described by Nadler [18]. There was no routine screening for thromboembolic events. However, all clinically

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suspicious scenarios were investigated by either duplex ultrasound or CT angiography for

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suspected DVT or PE, respectively.

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Trial Registration and Data Analysis

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The trial was approved by our institutional review board and registered with

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clinicaltrials.gov (National Institutes of Health Registry, NCT01683955). All patients provided

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preoperative informed consent to participate in the study.

The two groups were compared using chi-square and Fisher’s exact tests for the binary

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and categorical variables. Continuous variables were reported as mean ± standard deviation,

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median and range. Normally distributed continuous variables were compared using two-sided

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two-sample t-tests, and non-normally distributed continuous variables, such as length of stay

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(LOS), were compared using two-sided Wilcoxon rank-sum tests.

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Source of Funding

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The study was funded exclusively through the Department of Orthopaedic Surgery, Henry Ford

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Hospital, Detroit, USA. No external funding was used.

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Results

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Patient Recruitment and Characteristics

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From January 1st 2013 until October 31st 2013, 232 primary THAs were scheduled and completed. One-hundred and eight-four of these were deemed eligible for the study, 48 met 5

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exclusion criteria and 45 declined enrollment. One-hundred and thirty-nine went on to consent

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for study participation; 70 received the IV preparation and 69 received the local preparation

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(Fig.1). All 139 consented patients underwent an intention-to-treat analysis. The two groups

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demonstrated similar characteristics at baseline indicating a successful randomization process

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(Table II). There was an uneven distribution of patients across surgeons with a range of 12-45

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patients per surgeon (p=0.97).

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Blood Loss and Hemoglobin Change

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The IV group demonstrated higher post-operative hemoglobin prior to discharge compared to the topical group. Differences in lowest post-op hemoglobin (10.4 ± 1.6 g/dl vs. 9.7

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± 1.6 g/dl; p=0.008), change in hemoglobin (-3.1 ± 1.2 g/dL vs. -3.5 ± 1.2 g/dL p= 0.014) were

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significantly improved in the IV group. The IV mode resulted in less calculated Hgb loss (160.3 ±

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63.8 mg vs.188.4 ± 68.5; p= 0.014) and calculated blood loss (1,195.0 ± 485.9 mL vs. 1,442.7 ±

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562.7 mL; p=0.006) (Table III).

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Transfusion Rate

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The transfusion rate was 14% (n=20) for all patients, with the IV group having a lower rate compared to the topical group (11% vs 18%, p=0.3) (Table III). The historic transfusion

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rate from 2009-2011 for primary THA was identified to be 34%. Using this data, the number

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needed to treat (NNT) to prevent one transfusion was 5 and 7 patients for IV and topical TXA

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preparations, respectively.

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Cost Analysis

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Chemoprophylaxis and Postoperative Complications

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There was no statistical difference between the groups with respect to type of postoperative chemoprophylaxis against DVT and PE (Fig.2). There were 6 patients with a post6

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operative complication (2 from the IV and 4 from the topical groups, p=0.441). Three patients,

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developed a type II non-ST elevation myocardial infarction NSTEMI, 1 in the IV and 2 in the

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topical groups (p=0.619). No patients experienced a DVT and one patient in the IV group

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developed a PE.

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Discussion

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There is a growing body of evidence that TXA can reduce blood loss and transfusion rates in various surgical procedures including total hip arthroplasty [12, 19-21]. Several studies

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have analyzed the effect of intravenous TXA or topical TXA in total hip arthroplasty. However,

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none have compared the two routes of delivery in a prospective randomized control trial. Our

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goal in this study was to determine differences in IV and topical TXA delivery in THA with

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respect to blood loss and transfusion rate.

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Blood Loss and Transfusion Rates

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The experimental group received a topical solution of TXA prior to fascial closure and reduced

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their overall transfusion rate by greater than 50%, from 35-17% [14]. Pei et al. were also able to

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demonstrate a significant reduction in bloodloss and transfusion rate from 22% to 6% (P<0.05)

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in their RCT using 3g of topical TXA versus placebo in primary uncemented THA [22]. Alshryda

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et al performed a double-blind, randomized controlled trial of 161 patients undergoing unilateral

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primary THA investigating the effect of topical application of TXA on blood loss [11]. TXA

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reduced the absolute risk of blood transfusion by 19.6% (95% confidence interval [CI], 6.9% to

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32.1%; p = 0.004), from 32.1% to 12.5% [11].

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IV administration of TXA in primary THA has also shown to be effective at reducing

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transfusion rates. A 2015 randomized trial from the Bone and Joint Journal looking at IV (2g

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divided) versus placebo TXA showed a reduction in transfusion rates p=0.021 [15]. In a second 7

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randomized trial, 124 patients were given a single 15mg/kg dose of IV TXA preoperatively and

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reduced their transfusion rate from 22% to 3% p<0.05 [23]. A meta-analysis of 11 published

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randomized control trials evaluated the effect of IV TXA in THA, concluding that TXA led to a

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significant reduction in the proportion of patients requiring allogeneic blood transfusion [16].

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The only study comparing the efficacy of IV versus topical administration of TXA is a

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retrospective review of 1595 THA’s, by Wind et al. They reviewed transfusion rates in patients

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receiving IV TXA, topical TXA and no treatment. The transfusion rates were 4.39% (p=<0.0001),

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12.86% (p=0.15) and 19.86% respectively [24].

This trial demonstrates a significant difference in post-op Hgb, change in Hgb, calculated

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Hgb loss, and calculated blood loss, all favoring the IV TXA group. There was no statistically

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significant difference between the two groups when comparing transfusion rate, similar to that in

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Wind et al. Many studies demonstrate a statistically significant decrease in transfusion rates in

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both intravenous and topical groups when compared to placebo [11, 12, 14-16, 19, 20, 22-25].

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Given the effectiveness of the topical solution, our trial was unable to detect a statistically

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significant difference between IV and topical TXA with respect to transfusion rates. However, we

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do believe a reduction in transfusion rates from 34% (our historical control) to 11% and 18% in

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the IV and topical groups respectively is clinically significant. Our institution currently advocates

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for intravenous administration of TXA, mainly for its ease of use and seamless integration into

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surgical workflow in addition to its superior efficacy.

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Financial Implications

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Several studies have demonstrated a cost reduction per THA if TXA is applied broadly in

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order to reduce transfusion requirements. Transfusion rates in primary THA vary widely across

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the united states with a range from 5 -80% and a mean of 18% [26]. Using our historic

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transfusion rate, prior to the use of TXA, of 34% in primary cementless THA, cost analysis using 8

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IV TXA demonstrated a savings of $314 USD per patient. Our cost analysis does not take into

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account the savings with TXA based on resultant shorter hospital stay by avoiding transfusion,

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or the increased cost of acute transfusion reactions or infection. This value is similar to other studies in the orthopaedic literature [11, 27-29]. Alshryda et

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al identified a net cost savings of £305 per patient (equivalent to ~500 USD), while taking into

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account the requisite increase in hospital stay [11]. As medicine continues to respond to

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pressures of fiscal responsibility and moves toward bundled payment for orthopaedic care, IV

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TXA could save larger centers hundreds of thousands of dollars annually.

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Strengths and Limitations

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A strength of our study lies within the study design; to our knowledge there are no other prospective, double blind, randomized control trials with greater than 100 subjects reported from

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a single institution comparing intravenous and topical TXA in primary uncemented THA. The

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patients were randomized by an independent (of the institution) research pharmacist and a

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biostatistician reviewed the results to maintain blinding of the patients and all staff involved in

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patient care. Both treatment and placebo solutions had the same physical characteristics to

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ensure that the health care professionals could not differentiate between the two groups.

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There were several potential limitations in our study. First, the variance in follow-up (3-11

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months) could create inconsistencies in reports of adverse outcomes if late-appearing. Also, our

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cost analysis is based on a historical control group. Our cost analysis was based on a historical

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transfusion figure, prior to the use of TXA. Although our historical control group had similar

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patient characteristics there are minor biases, for which we could not control. Additionally, our

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VTE prophylaxis was surgeon dependent, which may improve the generalizability of the results,

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as it provides a realistic comparison to the heterogeneous community protocols based on

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AAOS/AACP approved guidelines. However, the uncontrolled nature of an independent variable

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inherently introduces the chance of error within the study.

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In conclusion, IV and topical TXA are safe and cost-effective adjuncts which decrease blood loss after primary uncemented THA, and compared to placebo have been shown to

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reduce transfusion requirements. Although no significant difference between modes of

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administration was identified, the IV route of administration may be preferred, in the majority of

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patients, given the ease of integration into current care models.

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1. Mesko NW, Bachmann KR, Kovacevic D, Lograsso ME, O'Rourke C, Froimson MI. Thirty-Day Readmission Following Total Hip and Knee Arthroplasty - A Preliminary Single Institution Predictive Model. Journal of Arthroplasty, 2014 2. Myers E, O'Grady P, Dolan AM. The influence of preclinical anaemia on outcome following total hip replacement. Arch Orthop Trauma Surg 124(10): 699, 2004 3. Perioperative Allogeneic Blood Transfusion Is Associated With Surgical Site Infection After Abdominoperineal Resection-a Space for the Implementation of Patient Blood Management Strategies. Int Surg 100(5): 797, 2015 4. Immunomodulatory effects of allogeneic blood transfusions: clinical manifestations and mechanisms. Vox Sang 74(Suppl 2): 315, 1998 5. Callaghan JJ, Spitzer AI. Blood management and patient specific transfusion options in total joint replacement surgery. Iowa Orthop J 20: 36, 2000 6. Kirkley SA, Cowles J, Pellegrini VD, Harris CM, Boyd AD, Blumberg N. Blood transfusion and total joint replacement surgery: T helper 2 (TH2) cytokine secretion and clinical outcome. Transfus Med 8(3): 195, 1998 7. MacFarlane BJ, Marx L, Anquist K, Pineo G, Chenger J, Cassol E. Analysis of a protocol for an autologous blood transfusion program for total joint replacement surgery. Can J Surg 31(2): 126, 1988 8. De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, Schiavello R, Possati GF. Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. Journal of Thoracic & Cardiovascular Surgery 119(3): 575, 2000 9. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 89(4): 780, 2007 10. Georgiadis AG, Muh, S.J., Silverton, C.D., Weir, R.M., Laker, M.W. A prospective double-blind placebo controlled trial of topical tranexamic acid in total knee arthroplasty. J Arthroplasty 28(8 Suppl): 78, 2013 11. Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total knee replacement: a systematic review and meta-analysis. Journal of Bone & Joint Surgery - British Volume 93(12): 1577, 2011 12. Gilbody J, Dhotar HS, Perruccio AV, Davey JR. Topical Tranexamic Acid Reduces Transfusion Rates in Total Hip and Knee Arthroplasty. The Journal of Arthroplasty, 2013 13. Konig G, Hamlin BR, Waters JH. Topical Tranexamic Acid Reduces Blood Loss and Transfusion Rates in Total Hip and Total Knee Arthroplasty. The Journal of Arthroplasty 28(9): 1473, 2013 14. Chang CH CY, Chen DW,Ueng SW, Lee MS. Topical tranexamic acid reduces blood loss and transfusion rates associated with primary total hip arthroplasty. Clin Orthop Relat Res 472(5): 1552, 2014 15. Hsu CH LP, Kuo FC, Wang JW. A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study. Bone Joint J 97-B(7): 905, 2015 16. Sukeik M, Alshryda S, Haddad FS, Mason JM. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. Journal of Bone & Joint Surgery - British Volume 93(1): 39, 2011 17. Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg 19(12): 777, 2011 18. Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery 51(2): 224, 1962 19. Claeys MA, Vermeersch N, Haentjens P. Reduction of blood loss with tranexamic acid in primary total hip replacement surgery. Acta Chirurgica Belgica 107(4): 397, 2007

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20. Husted H, Blond L, Sonne-Holm S, Holm G, Jacobsen TW, Gebuhr P. Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients. Acta Orthopaedica Scandinavica 74(6): 665, 2003 21. Lemay E, Guay J, Cote C, Roy A. Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement. Canadian Journal of Anaesthesia 51(1): 31, 2004 22. Yue C KP, Yang P, Xie J, Pei F. Topical application of tranexamic acid in primary total hip arthroplasty: a randomized double-blind controlled trial. J Arthroplasty 29(12): 2452, 2014 23. Jaszczyk M KD, Kolodziej L, Kazimierczak A, Sarnecki P, Sieczka L. Effect of Single Preoperative Dose of Tranexamic Acid on Blood Loss and Transfusion in Hip Arthroplasty. Ortop Traumatol Rehabil 17(3): 265, 2015 24. Wind TC, Barfield WR, Moskal JT. The Effect of Tranexamic Acid on Transfusion Rate in Primary Total Hip Arthroplasty. The Journal of Arthroplasty, 2013 25. Gillette BP, DeSimone LJ, Trousdale RT, Pagnano MW, Sierra RJ. Low risk of thromboembolic complications with tranexamic acid after primary total hip and knee arthroplasty. Clin Orthop Relat Res 471(1): 150, 2013 26. Browne JA AF, Brown TE, Novicoff WM. Transfusion rates are increasing following total hip arthroplasty: risk factors and outcomes. J Arthroplasty 28(8 Suppl): 34, 2013 27. Harris RN MJ, Capps SG. Does tranexamic acid reduce blood transfusion cost for primary total hip arthroplasty? A case-control study. J Arthroplasty 30(2): 192, 2015 28. BP G, H MK, CM D, HM S, RT T, MW P, RJ S. Economic impact of tranexamic acid in healthy patients undergoing primary total hip and knee arthroplasty. J Arthroplasty 28(8 Suppl): 137, 2013 29. Cost analysis of use of tranexamic Acid to prevent major bleeding complications in hip and knee arthroplasty surgery. Am J Orthop (Belle Mead NJ) 43(10): E217, 2014

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Cemented Femoral or Acetabular Component Current Medical Management of DVT or PE Previous Embolic Stroke or SAH Active Liver Disease with Abnormal Coagulation Profile Alteration to Color Vision Epilepsy Previous Surgery on the Planned Operative Hip Current Treatment with OCP or HRT

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Table I Exclusion Criteria

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DVT=Deep Vein Thrombosis; PE=Pulmonary Embolism; SAH=Sub-Arachnoid Hemorrhage; OCP=Oral Contraceptive Pill; HRT=Hormone Replacement Therapy

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Table II Patient Characteristics of the Study Population Combined (N= 139)

IV TXA (N= 70)

Topical TXA (N= 69)

pvalue

Age ¶ (yr)

64.9 ± 11.3

64.1 ± 12.0

65.7 ± 10.6

0.396

77 ( 55%)

38 ( 54%)

39 ( 57%)

0.791

31.1 ± 5.9

31.1 ± 5.4

Anesthesia Type (g/s)

59 ( 43%) / 79 ( 57%)

ASA score 1 / 2 / 3 / 4

Male Sex 2

31.1 ± 6.4

0.991

26 ( 37%) / 44 ( 63%)

33 ( 49%) / 35 ( 51%)

0.176

1 ( 1%) /36 ( 26%) / 99 ( 72%) /1 ( 1%)

0 ( 0%) / 16 ( 23%) /

1 ( 1%) / 20 ( 29%) / 47 ( 68%) / 1 ( 1%)

0.449

Preoperative INR ¶

1.02 ± 0.06

1.03 ± 0.06

PTT ¶ (s)

30.2 ± 5.5

30.9 ± 4.9

234.0 ± 60.4

231.5 ± 67.4

13.3 ± 1.4

13.4 ± 1.3

Platelet count preop ¶

1.01

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52 ( 75%) / 0 ( 0%)

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BMI ¶ (kg/m )

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0.123

29.5 ± 6.1

0.173

236.6 ± 52.9

0.623

13.2 ± 1.4

0.323

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Table III: Primary Patient Outcomes in the Study Population IV (N= 70)

Topical (N= 69)

p-value

Lowest Postop Hgb ¶(g/dL)

10.4 ± 1.6

9.7 ± 1.6

0.008

Change in Hgb ¶ (g/dL)

-3.1 ± 1.2

-3.5 ± 1.2

0.014

160.3 ± 63.8

188.4 ± 68.5

0.014

Blood loss ¶ (mL)

1,195.0 ± 485.9

1,442.7 ± 562.7

0.006

Blood Transfusion

8 ( 11%)

12 ( 18%)

0.300*

Hgb loss ¶ (mg)

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¶ = The values are given as the mean and standard deviation; * Not significantly different

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Variable

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Figure 1 Flow chart of enrollment and randomization Figure 2

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M AN U

SC

RI PT

Perioperative chemoprophylaxis in topical and IV groups

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT