The Journal of Arthroplasty xxx (2014) xxx–xxx

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The Journal of Arthroplasty

journal homepage: www.arthroplastyjournal.org

Cost Benefit Analysis of Topical Tranexamic Acid in Primary Total Hip and
Knee Arthroplasty
John R. Tuttle, MD, MS, Scott A. Ritterman, MD, Dale B. Cassidy, MD, MBA, Walter A. Anazonwu, BS,
John A. Froehlich, MD, MBA, Lee E. Rubin, MD
Department of Orthopaedics, Brown University Alpert School of Medicine, Providence, Rhode Island

a r t i c l e i n f o a b s t r a c t

Article history: The purpose of this study was to provide a cost–benefit analysis of topical tranexamic acid (TXA) in primary
Received 23 September 2013 total hip and knee arthroplasty patients. A retrospective cohort of 591 consecutive patients, 311 experimental
Accepted 27 January 2014 and 280 control, revealed a transfusion rate reduction from 17.5% to 5.5%, increased postoperative
Available online xxxx
hemoglobin, and decreased delta hemoglobin without an increase in adverse events (all Pb0.001). This led to
saving $83.73 per patient based on transfusion costs alone after accounting for the cost of TXA. Hospital
Keywords:
tranexamic acid
disposition to home compared to subacute nursing facility was also significantly increased by 9.3% (Pb0.02).
primary arthroplasty We conclude that topical TXA reduces transfusion rate, increases home disposition, and reduces cost in
transfusion primary hip and knee arthroplasty.
financial © 2014 Elsevier Inc. All rights reserved.

With growing public scrutiny for the provision of ever more
efficient and effective health care, orthopaedists bear increasing
pressure to minimize costs yet maintain quality care. The reduction of
perioperative blood transfusions in total joint arthroplasty has been
an ongoing effort with this goal in mind. Perioperative transfusion
adds both cost to the procedure and risk to the patient, including joint
infection, allergic reaction, and viral transmission [1–3]. This has led
us to analyze the cost benefit ratio of topical tranexamic acid (TXA) in
primary hip and knee arthroplasty.
Tranexamic acid is a synthetic derivative of the amino acid lysine
which produces antifibrinolytic activity by competitively inhibiting
lysine binding sites on plasminogen molecules. Through this process,
it is believed that TXA is able to help the body retain blood clots more
effectively and thereby reduce bleeding.
Several recent studies have sought to elicit the clinical outcomes of
TXA in total joint arthroplasty. Most protocols have involved
intravenous delivery of TXA, revealing impressive results [4,5]. An
oral form of TXA has also been shown to be effective [6]. While these
studies have not shown adverse events caused by TXA such as
increased thromboembolic events, this continues to be a concern, and
is perhaps why TXA implementation has been slow to progress. A
growing number of studies indicate that intraarticular injection or
topical administration may provide some advantages; these include
potentially reduced costs with a single injection, surgeon control, and
localization and concentration of the drug to the surgical site. Topical
application increases efficacy where it is intended as well as reduces
The Conflict of Interest statement associated with this article can be found at http://
dx.doi.org/10.1016/j.arth.2014.01.031.
Reprint requests: John R. Tuttle, 593 Eddy St. Providence, RI 02903.
possible side effects by minimizing systemic exposure. Recently
published studies have shown decreased transfusion rates and
reduced swelling with topical TXA in total knee arthroplasty without
increased complications [6–8].
The primary goal of this study was to determine whether initiation
of topical TXA in total hip and knee arthroplasty at our institution has
reduced transfusion rates, reduced costs, altered complication rates,
and reduced hospitalization times. The secondary goal was to provide
a description of an effective method for topical TXA administration in
total hip and knee arthroplasty.
Materials and Methods
Following IRB approval, 591 primary, consecutive total joint
arthroplasties performed by 5 orthopaedic surgeons at a single
institution between March 2012 and March 2013 were retrospective-
ly reviewed. September 1st 2012 marked the day that each of these
surgeons began to administer topical TXA to all total joint patients
intraoperatively. The months of August and September of 2012 were
excluded from the study to prevent overlap of the experimental and
control groups. The proportion of patients was similar between the
two cohorts for each surgeon. Bilateral total joints, revision joints, and
fractures requiring arthroplasty were excluded from the study.
Patients underwent either spinal, regional block or general
anesthesia as determined on a case by case basis. Patients received
local 0.5% Marcaine without epinephrine at the operative site after
wound closure. All patients received preoperative antibiotics within
1 h of surgical incision, typically cefazolin, vancomycin if MRSA
history present, or clindamycin if significant cephalosporin allergy.

0883-5403/0000-0000$36.00/0 – see front matter © 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.arth.2014.01.031

Please cite this article as: Tuttle JR, et al, Cost Benefit Analysis of Topical Tranexamic Acid in Primary Total Hip and Knee Arthroplasty, J
Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.01.031
2 J.R. Tuttle et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx

For TKA, following release of the tourniquet, electrocautery was Table 2

used to achieve hemostasis. Capsular closure was then performed. Primary Outcomes.

One gram of TXA in 10 cc of normal saline was injected intraarticu- No TXA (N = 280) TXA (N = 311) P Value
larly in total knees. For THA, one gram of TXA in 10 cc of normal saline Length of stay (days) 3.16±0.75 3.15±1.12 0.84
was injected in the pericapsular and deep tissue spaces or intraarti- Disposition home 174 222 b0.02
cularly following iliotibial band or tensor fascia closure depending on Disposition SNF 106 89 b0.02
the surgeon’s preference. Multi-modal postoperative DVT prophylaxis Readmission 12 13 N0.5
Complications 3 2 N0.5
was used including thromboembolism-deterrent stockings, sequen-
Postoperative Hgb 9.17±1.25 10±1.33 b0.001
tial compression devices, and chemical prophylaxis. One surgeon used Delta Hgb 4.5±1.11 3.8±1.31 b0.001
postoperative aspirin for chemical DVT prophylaxis while the other Patients transfused 49 17 b0.001
four used Coumadin. No intraoperative drains were placed. No Units Transfused 80 33 b0.001
changes were made to each surgeon’s individual surgical and Data reported as mean±SD or total sum. P values calculated using either independent
postoperative protocols between the control and experimental T-test or chi square test.
groups. No primary, unilateral total joint patients were excluded
from TXA use. Transfusion was triggered by a hemoglobin of less than
8 g/dL or symptomatic anemia for all patients in both control and and the TXA group being 10.0±1.33 g/dL (P b 0.0001 as calculated by
experimental groups. independent t-test). The resultant delta hemoglobin values are 4.5 g/
Each chart was reviewed via the electronic medical record and the dL and 3.9 g/dL for control and TXA groups, respectively (P b 0.0001).
following variables were obtained: age, gender, BMI, transfusions, Chi square analysis reveals a significant difference in number of
preoperative hemoglobin, postoperative hemoglobin, operative time, RBC units transfused between the groups. The control group required
tourniquet time, days in hospital, 30 day readmission, disposition to 80 U RBC for 280 patients to be transfused while the TXA group
home or subacute nursing facility, and complications including UTI, required only 33 U for 311 patients. That is 10.6% units transfused
MI, DVT, stroke and death. No routine screening for DVT/PE was after TXA implementation down from 28.6% prior, a reduction of 18%
performed. Symptomatic DVT was confirmed by ultrasound. (P b 0.001). Of the 80 U transfused in the control group, 39 U went to
The blood transfusion cost was estimated using prior published THA patients (48.8%). In the TXA group, 13 U of the 33 U (39.4%) went
data [9] and confirmed with our hospital Blood Bank. Transfusion cost to THA patients. While a relatively larger number of RBC units went to
per 1 U RBC was estimated to be $726 in 2008 at our institution. THA in the control group, this result was not significant (P N 0.5). The
Adjusted for inflation, this cost was $787.37 in 2013. The cost of 1 g of control group required 49 patients to be transfused. The TXA group
TXA was approximately $58 in 2013 at our institution. Preoperative required 17 patients to be transfused. That is a 17.5% transfusion rate
hemoglobin was obtained within 30 days of surgery. Postoperative reduced to 5.5%, a reduction of 12% (P b 0.001).
hemoglobin was obtained daily while the patient was hospitalized; Chi square analysis was applied to show a significant difference in
the lowest hemoglobin was recorded for analysis. Readmissions post hospital disposition. In the control group, 174 of 280 patients
within 30 days were recorded regardless of indication. (62.1%) went home as opposed to subacute nursing facility. In the TXA
Statistical analysis was used to confirm the significance of the group, 222 of 311 patients, (71.4%) went home, P b 0.02.
results. The chi square test was used for discrete variables such as Tourniquet time, operative time, and time in room averaged 54,
transfusion rate and hospital disposition. Independent t-tests were 101.2, and 139.7 min respectively for the control group. Tourni-
used for continuous variables such as drop in hemoglobin, BMI, age, quet time, operative time, and time in room averaged 64.7, 121.5,
etc. Statistical significance was defined as P b 0.05. and 140.8 min respectively for the TXA group. The difference was
not statistically significant. Number of days in the hospital
remained nearly the same between each group. The control
Results
group averaged 3.16 ± 0.75 days while the TXA group averaged
3.15 ± 1.12 days (P = 0.93).
There was no statistically significant difference in demographics
Adverse events were similar between each group. The control
between the pre and post TXA groups. The control group (280
group experienced 2 UTIs and 1 symptomatic DVT in the 30 day
patients) consisted of 169 TKA and 111 THA; TKA made up 60.4% of
postoperative period. The TXA group suffered 1 UTI and 1 MI. Twelve
the control group cases. The experimental TXA group (311 patients)
patients in the control group were readmitted within 30 days while
consisted of 185 TKA and 126 THA; TKA made up 59.5% of the
13 were readmitted in the TXA group. No patient in either group
experimental group cases. Demographics are summarized in Table 1.
required reoperation in the 30 day postoperative period for any
This shows a nearly identical patient population in terms of gender,
reason, including infection or hematoma evacuation. Primary out-
age, BMI, preoperative hemoglobin, and surgical procedure.
comes are available in Table 2.
The preoperative hemoglobin levels were similar with the control
Cost analysis was based solely on transfusion rate reduction. With
group being a mean of 13.7±1.38 g/dL and the TXA group being 13.9
a transfusion cost of $787.37 and a 1 g of TXA cost of $58, there was a
±1.44 g/dL. There was a significant difference in postoperative
savings of $8372.66 per 100 arthroplasty patients treated. In full
hemoglobin however, with the control group being 9.17±1.25 g/dL

Table 1 Table 3
Demographics. Transfusion Financial Summary.

No TXA (N = 280) TXA(N = 311) P Value No TXA (N = 280) TXA (N = 311) Difference

Age (years) 66.1±11.26 65.2±10.55 0.33 Total transfusion cost (USD) $62,989.60 $25,983.21 $37,006.39
Male 113 131 N0.5 Transfusion Cost for TKA $32,282.17 $15,747.40 $16,534.77
Female 167 180 N0.5 Transfusion Cost for THA $30,707.43 $10,235.81 $20,471.62
Total Hip 111 126 N0.5 Units Transfused (%) 28.6% 10.6% 18%
Total Knee 169 185 N0.5 Transfusion Cost per 100 pts $22,518.78 $8346.12 $14,172.66
BMI 31.5±6.3 31.5±6.5 0.91 Patients Transfused 17.5% 5.5% 12%
Preoperative Hgb 13.7±1.38 13.9±1.44 0.12 Cost per patient $225.19 $141.46 $83.73

Data reported as mean ± SD or total sum. P values calculated using either independent United States Dollar (USD). Transfusion cost assumes $787.37 per unit PRBC. TXA cost
T-test or chi square test. assumes $58 per 1 g.

Please cite this article as: Tuttle JR, et al, Cost Benefit Analysis of Topical Tranexamic Acid in Primary Total Hip and Knee Arthroplasty, J
Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.01.031
 J.R. Tuttle et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
discussion, 100 arthroplasty patients receive TXA at $58 apiece, or
$5800 total. With an observed reduction of allogeneic units transfused
by 18% with TXA then ($787.37*18) = $14,172.66 saved for every
100 patients treated. By subtracting the acquisition costs of the TXA
($5800) from this value, we found a net savings of $8372.66 per 100
treated, amounting to $83.73 per patient. See Table 3 for financial
summary.
Discussion
Our institution has seen a marked reduction in transfusion rates
since the implementation of topical TXA in total joint arthroplasty. We
noted a 12% reduction in postoperative transfusion and an 18%
reduction in the rate of RBC units transfused. The postoperative
hemoglobin levels were significantly higher in the TXA group. The use
of TXA saved $8372.66 per 100 patients based on transfusion cost
alone. This amount does not factor in the cost of transfusion-related
total joint complications. Parvizi et al estimated a cost of $68–107 K
per total joint infection depending on the organism type [10]. Greater
healthcare savings may be recognized if variables such as transfusion
complication or infection rates are included in the cost analysis.
There was a significant difference in preparedness for discharge to
home between the two groups. The TXA group had a 9.3% higher
likelihood of going home instead of a skilled nursing facility (SNF).
Patients are slower to mobilize due to the time requirement of
transfusion and missed physical therapy sessions. At our institution, if
the patients have not proven they will be safe at home by the third
postoperative day, SNF becomes the default disposition. Our hypoth-
esis that the control group would require a longer hospital stay did not
prove to be true. However, had these patients not gone to SNFs, they
would have required a longer hospital stay. TXA reduces time
required in a health care facility. These data were not included in
the cost benefit analysis. In 2008, Mahomed et al concluded that over
$3000 CAD could be saved per patient if they received home versus
inpatient rehabilitation [11]. We predict this would further reduce
economic burden on the healthcare system and add favorably to the
overall cost–benefit analysis in favor of TXA utilization. There were no
significant differences in complication rates between the two groups.
Consistent with the literature, no significantly increased risk of DVT,
PE, MI, or stroke with topical TXA use was evident [8–12]. Admittedly,
this study consisted of just 591 patients and is underpowered to
definitively determine differences in these rates. However, appropri-
ately powered studies such as the CRASH-2 study have shown no
statistically significant increase in vascular occlusive events with the
intravenous use of TXA in trauma patients [13]. An adequately
powered, prospective, randomized control trial for primary hip and
knee arthroplasty would provide a more definitive analysis.
This study suffers from several limitations. The strength of the
study is limited by its retrospective nature. Complications that either
did not occur in the hospital setting or did not require readmission
were not recorded due to database limitations. Each surgeon followed
his own protocol and used implants from three different companies.
Different surgical approaches for total hip arthroplasty were utilized,
including direct anterior, anterolateral, and posterior, depending on
the surgeon. Likewise, closure techniques differ slightly between each
surgeon. TXA injection in THA was not standardized, and therefore
some surgeons injected intraarticularly while others injected into
both the intra-articular space and the pericapsular tissues. Postoper-
ative chemical DVT prophylaxis differed among surgeons as well.
Further prospective, standardized, multi-center analysis may be
warranted to delineate the significance of these variables.
There are several alternatives that have been studied to reduce
transfusions in primary total joint arthroplasty. These options include
predonation of autologous blood for possible postoperative use, red
cell salvage technology, recombinant human erythropoietin (Epo),
and aprotinin. Autologous predonation has been associated with
Please cite this article as: Tuttle JR, et al, Cost Benefit Analysis of Topical Tranexamic Acid in Primary Total Hip and Knee Arthroplasty, J
Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.01.031
3
several negative events including increased vasovagal complications,
increased transfusion rates, and absence of cost effectiveness [14,15].
Friederichs et al compared predonation to cell saver and determined
that predonation acquisition alone averaged $145 per unit while cell
saver cost $386 per patient at their institution [16]. Guerra et al noted
that intraoperative blood salvage would have to average 3 U of RBC
obtained per patient to be cost effective. They averaged 2 U per
patient and concluded it was not cost effective [17]. A meta-analysis
performed by Coyle et al determined that costs outweigh the benefit
of Epo use in orthopaedic surgery at this time [18]. Aprotinin has not
proven effective in orthopaedic procedures in low doses and may
cause adverse renal events in higher doses [19].
When compared to IV administration of TXA in TKA, topical TXA
was equally effective at transfusion reduction [4,12]. Seo et al
concluded that topical TXA was more effective than IV TXA in TKA
[20]. Systemic absorption is 70% lower with topical TXA than IV TXA,
which may lead to fewer systemic complications [12]. Fewer studies
have evaluated topical TXA in THA. The retrospective study from
Wind et al failed to show a decrease in transfusion rate with topical
TXA, but did note a significant reduction with IV TXA compared to
their control group [5]. However, Konig et al mirrored our results,
showing a statistically significant reduction in THA transfusion rates
with topical TXA [21]. Gillette et al provide a cost benefit analysis of IV
TXA in THA and TKA in which they indicate a cost of $140 for IV TXA
per patient [22]. This is nearly 150% of the cost of topical TXA at our
institution. Chimento et al recently published a cost benefit analysis of
topical TXA in TKA using total hospitalization costs and found it saved
approximately $1500 per patient [8]. A randomized control trial was
recently performed by Georgiadis et al which concluded that topical
TXA in TKA reduced blood loss and did not increase thromboembolic
events [23]. Lee et al showed similar results when combined with
postoperative fondaparinux [24]. Based on this information and the
results of our study, topical TXA appears to be a viable and cost-
effective alternative to IV TXA.
This study offers a cost–benefit analysis of topical TXA in
primary hip and knee arthroplasty at a single joint center.
Transfusion rates dropped by 12%. Approximately 9.3% more
patients were able to be discharged home rather than to a skilled
nursing facility. There was no significant difference in complication
rate associated with the use of TXA. Our institution saved an
average of $83.73 per patient after accounting for the acquisition
costs of TXA and allogeneic blood in 2013 dollars. Although
prospective randomized controlled trials are necessary for defini-
tive recommendations regarding the safety of a therapeutic drug in
a large population of patients undergoing TKA and THA, our study
makes a strong case to support the use of topical tranexamic acid in
all primary hip and knee arthroplasties.
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Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.01.031
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