INTRAARTICULAR EPSILON AMINOCAPROIC ACID VERSUS TRANEXAMIC ACID IN TOTAL KNEE ARTHROPLASTY

Abstract

Objective:
To examine and compare the clinical efficacy of intraarticular epsilon aminocaproic acid (EACA) and tranexamic acid (TXA) in total knee arthroplasty (TKA).

Methods:
This study was a prospective, single-center, double-blinded randomized controlled trial, including sixty patients with osteoarthritis of the knee divided into two groups of 30 patients. In the TXA group, 1 g of TXA (0.05 g/ml) was applied intraarticularly, and in the EACA group, 4 g of EACA (0.2 g/ml) was applied intraarticularly. Serum hemoglobin (Hgb) and hematocrit (Htb) were measured during the preoperatively and 24 and 48 hours postoperatively. The range of motion and pain were evaluated by clinical examination. To evaluate knee function before and 2 months after surgery, the Western Ontario and McMaster Universities Index (WOMAC) questionnaire was used.

Results:
In total, 56 (93.3%) patients were evaluated up to the second postoperative month. No significant difference between the groups (p > 0.05) was found in the decrease in Hgb or Htb at 24 or 48 hours. Regarding assessment of the pain, WOMAC score and gain in knee flexion, no significant advantages up to 60 days after surgery (p > 0.05) were found.

Conclusions:
The decrease in Hgb and Htb during the first 48 hours postoperatively and the risk of transfusion were similar with the intraarticular use of 1 g of TXA and 4 g of EACA in TKA. The possible benefits regarding knee pain, gain in flexion and function were also similar for the two drugs. Level of Evidence II, Randomized, Double-Blinded, Single-Centre, Prospective Clinical Trial.

Full text

Acta Ortop Bras. 2021;29(6):312-315
312
DOI: http://dx.doi.org/10.1590/1413-785220212906242008
Knee
Original Article
Citation: Guerreiro JPF, Balbino JRM, Rodrigues BP, Danieli MV, Queiroz AO, Cataneo DC. Intraarticular epsilon aminocaproic acid versus tranexamic
acid in total knee arthroplasty. Acta Ortop Bras. [online]. 2021;29(6):312-315. Available from URL: http://www.scielo.br/aob.
The study was conducted at Hospital Evangélico de Londrina.
Correspondence: João Paulo Fernandes Guerreiro. Av. Higienópolis, 2.600, Londrina, PR, Brazil, 86050170. drjoaopauloguerreiro@gmail.com
All authors declare no potential conict of interest related to this article.
Arti cle received on 0 8/10/2020, app roved on 10/20/20 20.
INTRAARTICULAR EPSILON AMINOCAPROIC ACID VERSUS
TRANEXAMIC ACID IN TOTAL KNEE ARTHROPLASTY
ACIDO ÉPSILON AMINOCAPROICO INTRA-ARTICULAR VERSUS
ACIDO TRANEXÂMICO NA PRÓTESE TOTAL DO JOELHO
Joao Paulo Fernandes Guerreiro1,2,3 , Jose Rodolfo Martines Balbino2 , Bruno Possani Rodrigues2 ,
Marcus Vinicius Danieli1,2,3 , Alexandre Oliveira Queiroz2 , Daniele Cristina Cataneo3
1. Uniort.e Orthopedic Hospital, Londrina, PR, Brazil.
2. Londrina Evangelic Hospital, Londrina, PR, Brazil.
3. Universidade Estadual Paulista Júlio de Mesquita Filho, Botucatu, SP, Brazil.
ABSTRACT
Objective: To examine and compare the clinical efficacy of intraar-
ticular epsilon aminocaproic acid (EACA) and tranexamic acid
(TXA) in total knee arthroplasty (TKA). Methods: This study was a
prospective, single-center, double-blinded randomized controlled
trial, including sixty patients with osteoarthritis of the knee divided
into two groups of 30 patients. In the TX A group, 1 g of TXA (0.05 g/
ml) was applied intraarticularly, and in the EACA group, 4 g of EACA
(0.2 g/ml) was applied intraarticularly. Serum hemoglobin (Hgb)
and hematocrit (Htb) were measured during the preoperatively
and 24 and 48 hours postoperatively. The range of motion and
pain were evaluated by clinical examination. To evaluate knee
function before and 2 months after surgery, the Western Ontario
and McMaster Universities Index (WOMAC) questionnaire was
used. Results: In total, 56 (93.3%) patients were evaluated up to
the second postoperative month. No significant difference between
the groups (p > 0.05) was found in the decrease in Hgb or Htb at
24 or 48 hours. Regarding assessment of the pain, WOMAC score
and gain in knee flexion, no significant advantages up to 60 days
after surgery (p > 0.05) were found. Conclusions: The decrease
in Hgb and Htb during the first 48 hours postoperatively and the
risk of transfusion were similar with the intraarticular use of 1 g
of TXA and 4 g of EACA in TK A. The possible benefits regarding
knee pain, gain in flexion and function were also similar for the
two drugs. Level of Evidence II, Randomized, Double-Blinded,
Single-Centre, Prospective Clinical Trial.
Keywords: Total Knee Arthroplasty. Bleeding. Pain. Tranexamic
Acid. Epsilon Aminocaproic Acid.
RESUMO
Objetivo: Avaliar e comparar a eficácia clinica do uso intra-articular
do ácido épsilon aminocaproico (AEAC) versus o ácido tranexâmico
(ATX) na prótese total do joelho. Métodos: Estudo clínico prospectivo,
centro-único, duplo-cego e randomizado. Sessenta pacientes com
osteoartrose de joelho foram incluídos. Os participantes foram dividi-
dos em dois grupos de 30 pacientes. No grupo ATX, foi aplicado 1 g
de ATX (0.05 g/ml) intra-articular e, no grupo AEAC, foram aplicados
4 g de AEAC (0.2 g/ml) intra-articular. Valores séricos da hemoglobina
(Hb) e hemtatócrito (Ht) foram dosados no pré-operatório e com
24 e 48 horas após a cirurgia. A amplitude de movimento e a dor
também foram avaliadas no exame clínico. O índice WOMAC foi
utilizado para avaliar a função do joelho antes e após dois meses
da cirurgia. Resultados: Foram avaliados 56 (93.3%) pacientes até
o segundo mês pós-operatório. Depois da cirurgia, não houve
diferenças entre os grupos (p > 0.05) na queda do valor de Hb e
Ht com 24 ou 48 horas. Com relação à avaliação da dor, WOMAC
e ganho de flexão do joelho, não houve vantagem significativa para
nenhum dos grupos até os 60 dias depois da cirurgia(p > 0.05).
Conclusão: A queda do valor da Hb e do Ht durante as primeiras 48
horas pós-operatórias e o risco de transfusão foram similares com
o uso intra-articular de 1 g de ATX e 4 g de AEAC na artroplastia
total do joelho. Os possíveis benefícios com relação ao controle da
dor, ganho de flexão e função foram similares entre as duas drogas.
Nível de Evidência II, Ensaio-Clínico Prospectivo, Randomizado,
Duplo Cego, Centro-Único.
Descritores: Artroplastia Total do Joelho. Sangramento. Dor. Ácido
Tranexâmico. Ácido Épsilon Aminocapróico.
INTRODUCTION
Antifibrinolytics have already been successfully used to reduce
the need for transfusion in total knee arthroplasty ( TKA).1-3 TKA
is associated with considerable blood loss.3 Besides the risk
of transfusion, excessive bleeding can impair the success of
TKA through hematoma, swelling, stiffness, prolonged hospi-
talization, and delayed functional recovery and rehabilitation.3
Epsilon aminocaproic acid (EACA) and tranexamic acid (TXA)

313
Acta Ortop Bras. 2021;29(6):312-315
are synthetic amino acid derivatives that interfere with fibrinolysis
and promote hemostasis. Although the clinical efficacy of TXA
in decreasing blood loss, improving the hemoglobin (Hgb)
level and improving some functional parameters, such as pain
and flexion, have been well demonstrated in TKA,4 data on the
effects of EACA in TKA have been reported in few published
studies to date, and those studies have only investigated the
intravenous use of EACA.2,5,6 Due to the scarcity of this data,
most surgeons prefer TXA over E ACA, despite its higher cost
in many countries.1,6
To our knowledge, this was the first trial of intraarticular EACA
and TX A in TKA to determine if apparent differences in efficacy
can be found.
The primar y aim of this prospective, randomized trial was to
examine and compare the clinical efficacy of intraarticular EACA
and TX A in TKA. The study questions were if EACA and TXA were
similar regarding blood conservation (defined by the transfusion
rate and drop in Hgb and hematocrit [Htb]), postoperative pain
control and postoperative gain in knee flexion; possible associ-
ations that have not yet been described were identified using a
functional questionnaire.
Our hypothesis was that intraarticular TXA would be similar to
intraarticular EACA in terms of antifibrinolytic effects after TK A.
MATERIALS AND METHODS
This study was a prospective, single-center, double-blinded ran-
domized trial. The project was approved by Institution Ethics and
Research Committee in July 2017 and was assigned the clinical trial
in December 2017. All patients provided written informed consent
to participate in the study.
Study population
During recruitment, between July 2017 and December 2018,
patients (of both sexes) that had three-compartment osteoarthritis
of the knee as an indication for TKA and were awaiting scheduling
of the procedure, had no diagnosis of inflammatory disease, had
no history of atrial fibrillation, pulmonary embolism, deep vein
thrombosis, or surgery on the same knee, had no coagulopathy
and were not using anticoagulant medications were eligible for
inclusion. The TKA procedures were performed between October
2017 and July 2019. Inadequate closure of the joint capsule at the
end of surgery, with identified leakage of the drug applied to the
joint, was considered an exclusion criterion. The last follow-up
was in September 2019.
Interventions
The blood of the patients was collected for serum Hgb and Htb
measurements before surgery, in the operating room. Knee
arthroplasty was performed with a standard medial parapatellar
approach by two surgeons from the same hospital. A tourniquet
was used in all subjects during the surgery until the wound
was dressed. Cemented cruciate-substituting implants without
patellar resurfacing were used in all procedures. After joint
capsule closure, the surgeon left the operating room, and the
random group assignment of the patient, determined using an
electronic randomization program to divide the participants into
2 groups of 30 patients, was revealed. No patient was informed
of the group assigned. In the TXA group, the auxiliary surgeon
applied 1 g of TXA (0.05 g/ml) intraarticularly using a 20 ml
syringe and a 40 × 1.2 mm needle before the operative wound
was sutured (Figure 1). In the EACA group, the auxiliary surgeon
applied 4 g of EACA (0.2 g/ml) intraarticularly using a 20 ml
syringe and a 40 × 1.2 mm needle before the operative wound
was sutured (Figure 1).
Figure 1. Application of drug in the joint cavity after joint capsule closure.
Data collection
Data were collected before and after surger y, as follows (Table 1):
Table 1. Model of the worksheet used for data collection at the different
time points (before and after surgery).
Before 24 h 48 h 20 days 60 days
Hgb x x x
Htb x x x
Knee flexion x x x x
Pain x x x x
WOMAC x x
Transfusion x x
Surgical site x x x x
Signs of infection x x
Hgb: hemoglobin; Htb: hematocrit; pain: evaluation of pain on a numerical scale; WOMAC: evaluation
of the Weste rn Ontario an d McMaster Uni versities Ind ex; transfusi on: assessmen t of the need for
blood tr ansfusion; sur gical site: obse rvation of the h ealing status; s igns of infectio n: assessment
of serum te st results and t he need for anti biotic ther apy, surgical de bridement o r implant remo val.
1.
Serum Hgb and Htb were measured during the preoperative
period and also 24 and 48 hours after surgery. The need for
transfusion was evaluated for patients with values below 7 mg/
dL and clinical signs of acute anemia.
2.
The patients underwent clinical examinations at the following
postoperative time points: 24 hours, 48 hours, between 15 and
25 days, and 2 months after surgery. a) Range of motion was
evaluated using a goniometer. b) Pain was evaluated using an
11-point (0-10) numerical scale, on which zero indicated no pain,
and 10 indicated the most intense pain ever felt. Each patient
selected a single number that best represented the intensity of
their pain at the time of the evaluation. c) The surgical site was
evaluated by clinical examination.
3.
To evaluate knee function before and 2 months after surgery,
the Western Ontario and McMaster Universities Index (WOMAC)
questionnaire was used.
Postoperative protocol used
1.
During hospitalization, the following analgesics were prescribed:
1 g of intravenous dipyrone every 6 hours and 50 mg of tramadol
hydrochloride every 8 hours.
2. Patients with pain equal or above 7 on the numerical pain scale
received 4 mg of intravenous morphine every 4 hours, and this
grade was considered in the evaluation for that period.
3.
At the time of discharge, 1 g of dipyrone was given orally every
6 hours if there was pain, and 50 mg of tramadol hydrochloride

314 Acta Ortop Bras. 2021;29(6):312-315
was given orally every 8 hours if pain persisted despite the
use of dipyrone.
4.
All patients received 40 mg of subcutaneous enoxaparin as
prophylaxis for deep venous thrombosis in the hospital at 8,
24 and 48 hours after surgery, and 10 mg of rivaroxaban daily
was prescribed for another 10 days at home.
5.
Antibiotic prophylaxis was performed with 2 g of intravenous
cefazolin during anesthetic induction, and 1 g of cefazolin was
administered every 8 hours for 24 hours.
Statistical analysis
The statistical power of the sample was calculated using the sampsi
command of STATA software (version 11, 2011, College Station,
Texas, USA) for a comparative design of groups with repeated
measures and using the reduction in Hgb as the parameter, and
we found that 20 patients per group would guarantee a power of
at least 95% for comparisons.
Comparisons between the two groups at all times with respect to
all variables were performed using mixed-effects (random and fixed
effects) linear regression models. Post-test orthogonal contrasts were
used for comparisons. Intergroup comparisons regarding changes
in Hgb and Htb at certain times were performed using Student’s
t-test. The significance level adopted for all comparisons was 5%.
RESULTS
In this study, 60 patients, including 30 in the TXA group and 30 in
the EACA group, were followed until the second postoperative day
(Figure 2). In total, 56 (93.3%) patients were evaluated up to the second
postoperative month, including 27 (90%) in the TXA group and 29
(96.6%) in the EACA group. The mean patient age was 67.97 (41-85)
years in the TXA group and 68.67 (46-83) years in the EACA group. In
total, 22 women in the TXA group and 20 women in the EACA group
were included. The two groups were statistically similar preoperatively
regarding Hgb, Htb, knee flexion and WOMAC score (Table 2).
Table 2. Demographic data.
TXA group EACA group P value
Number of surgical patients 30 30 > 0.05
Number of patients followed
to the 2nd day 30 30 > 0.05
Number of patients followed
to the 2nd month 27 (90%) 29 (97%) > 0.05
Mean age 67.97
(41-85)
68.67
(46-83)
> 0.05
Sex (man/woman) 8/22 10/20 > 0.05
Preoperative hemoglobin value
(mean and standard deviation)
13.24
(1.48)
12.47
(1.6)
> 0.05
Preoperative hematocrit value
(mean and standard deviation)
38.49
(4.15)
37.95
(5.34) > 0.05
Preoperative knee flexion
(mean and standard deviation)
106.5
(13.84)
98.33
(10.77)
> 0.05
Preoperative WOMAC score
(mean and standard deviation)
66.93
(19.96)
68.57
(20.72) > 0.05
Table 3 shows that no significant difference (p > 0.05) was
found in the Hgb or Htb decrease at 24 or 48 hours after surgery
between the groups.
Table 3. Hgb and Htb.
TXA
group
(mean and
standard deviation)
EACA
group
(mean and
standard deviation)
P-value
Hgb drop at 24 hours 1.59 (1.11) 1.19 (0.82) > 0.05
Hgb drop at 48 hours 2.54 (1.18) 2.48 (1.22) > 0.05
Htb drop at 24 hours 4.82 (3.37) 3.68 (3.01) > 0.05
Htb drop at 48 hours 7.29 (3.42) 7.04 (4.05) > 0.05
Table 4 shows that no significant advantage was detected in either
group regarding either pain or gain in knee flexion at 24 hours, 48
hours, 20 days or 60 days after surgery (p > 0.05).
Table 4. Evaluation of pain and flexion gain.
TXA
group
(mean and
standard deviation)
EACA
group
(mean and
standard deviation)
P value
Mean pain at 24 hours 3.37 (2.58) 4.07 (3.17) > 0.05
Mean pain at 48 hours 3.1 (2.75) 3.31 (3) > 0.05
Mean pain at 20 days 2 (1.82) 2.24 (2.47) > 0.05
Mean pain at 60 days 1.36 (1.81) 1.59 (1.86) > 0.05
Flexion gain at 24 hours 66.17 (18.37) 74.17 (24.74) > 0.05
Flexion gain at 48 hours 74.83 (17.88) 76 (24.26) > 0.05
Flexion gain at 20 days 91.67 (12.89) 91.55 (15.18) > 0.05
Flexion gain at 60 days 97.96 (17) 98.1 (12.57) > 0.05
Regarding the WOMAC score, no differences between the two
groups were found up to 2 months after surgery (Table 5).
Table 5. Comparison of WOMAC score between groups.
TXA
group
(mean and
standard deviation)
EACA
group
(mean and
standard deviation)
P-value
WOMAC score
at 2 months 19.96 (8.5) 20.72 (11.71) > 0.05
Figure 2. CONSORT flowchart.
Assessed for eligibility (n = 61)
Randomized (n = 60)
Allocation
Follow-Up
Analysis
Allocated to TXA group (n = 30)
Received intra-articular TXA (n = 30)
Lost to follow-up (n = 0)
• 2nd day (n = 0)
• 2nd month (n = 0)
Analyzed until 2nd day (n = 30)
• Excluded from analysis
until 2nd day(n = 0)
Analyzed until 2nd month (n = 27)
• Excluded from analysis
until 2nd month(n = 3)
• Acute deep infection with
another surgery (n = 2)
• Femur fracture (n = 1)
Analyzed until 2nd day (n = 30)
• Excluded from analysis
until 2nd day(n = 0)
Analyzed until 2nd month (n = 29)
• Excluded from analysis
until 2nd month(n = 1)
• Death by heart attack (n = 1)
Excluded (n=1)
• Exclusion criteria (n = 1)
• Unable to closure of the joint capsule
Allocated to EACA group (n = 30)
• Received intra-articular EACA (n = 30)
Lost to follow-up (n = 1)
• 2nd day (n = 0)
• 2nd month (n = 1)
• Death by heart attack (n = 1)
Enrollment

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Acta Ortop Bras. 2021;29(6):312-315
During the follow-up of the 60 patients, four cases (6.7%) of wound
dehiscence and superficial infection were successfully treated with
dressings and oral antibiotics (two in the TXA group and two in the
EACA group). Two cases (3.3%) of acute deep infection were treated;
one required debridement, and one required implant removal (both
in the TX A group). One (1.7%) manipulation was performed to treat
arthrofibrosis (in the EACA group). In total, one (1.7%) diagnosed
case of thrombosis in the TXA group was identified. One (1.7%) case
of mortality due to a heart attack in the EACA group were detected.
No patients required a blood transfusion (the transfusion criterion
was an Hgb value less than 7 mg/dL in symptomatic patients).
The identified complications were not significantly associated with
EACA or TXA use (Table 6).
Table 6. Complications.
TXA
group
EACA
group Total
Wound dehiscence and
superficial infection 2 (3.3%) 2 (3.3%) 4 (6.7%)
Acute deep infection 2 (3.3%) 0 2 (3.3%)
Manipulation due to arthrofibrosis 0 1 (1.7%) 1 (1.7%)
Thrombosis 1 (1.7%) 0 1 (1.7%)
Death 0 1 (1.7%) 1 (1.7%)
Transfusion 0 0 0
Total patients 5 (8.3%) 4 (6.7%) 9 (15%)
DISCUSSION
EACA and TXA function by a similar mechanism. Supported by
robust scientific evidence, TX A is widely routinely used in TKA at
many orthopedic surgery centers, reducing the risk of transfusion
and costs.7 However, fewer studies have analyzed EACA or com-
pared the two drugs.3
We found only two clinical prospective studies in the literature, both of
which were small trials showing similar efficacy for TXA and EACA.
1,5
We found only a prior retrospective study including a large number
of patients that showed the same results.6 The doses of EACA were
at least 5 times higher than the doses of TXA in these studies, and
EACA was administered intravenously in all of them.1,5 ,6 This study
was the first to compare 1 g of TXA with 4 g of EACA administered
intraarticularly in TKA. In some situations, EACA is less expensive than
TXA1,6 ; proving that the effects are comparable providing additional
justification for its use, and this justification becomes even more robust
if an even lower dose can be used with the same efficacy. Several
publications have shown the noninferior effect of topical TXA over
intravenous TXA.
8,9
When given intravenously, minor gastrointestinal
symptoms, such as nausea and vomiting, have been reported.
10
Antifibrinolytic drugs are known to decrease perioperative bleeding
and prevent premature clot dissolution.
11
Surgeons can apply the
drug by themselves when administering it intraarticularly, and lower
doses can be used with less risk of systemic side effects.12,13
We determined pain control, knee flexion gain and knee function
by the WOMAC questionnaire in the groups up to two months
postoperatively, in addition to evaluating the drop in Hgb and Htb.
This study also shows that the possible benefits in pain control,
flexion gain and knee function demonstrated in some previous
studies using TXA were similar when using EACA.12 ,14
This study has some limitations. First, although we performed a power
analysis to determine the size of the study population, our study was
a small clinical trial at a single center. Second, we estimated bleeding
using only serum Hgb and Htb levels without calculating the blood
volume using the weight and height of the patients. Third, since we
did not use drains because we considered that a portion of the drug
applied intraarticularly could be lost through the drain, we could not
directly measure bleeding. Fourth, we did not determine the serum
drug levels achieved in the patients, and therefore, although we did
not observe any clinically evident side effects, we cannot determine
a difference in the safety of these drugs administered intraarticularly.
CONCLUSIONS
The drop in Hgb and Htb in the first 48 hours postoperatively and
the risk of transfusion were similar for 1 g of TX A and 4 g of EACA
administered intraarticularly in TKA. The possible benefits regarding
knee pain, flexion and function were also similar for the two drugs.
AUTHORS’ CONTRIBUTIONS: Each author contributed individually and significantly to the development of this article. JPFG: drafted and reviewed the
article, performed statistical analysis and contributed to the intellectual concept of the study and the entire research project; JRMB: drafted the article, sou-
ght volunteers and analyzed the data; BPR: drafted the article, sought volunteers and analyzed the data; MVD: reviewed the article and contributed to the
intellectual concept of the study; AOQ: reviewed the article and contributed to the intellectual concept of the study; DCC: reviewed the article and contributed
to the intellectual concept of the study.
REFERENCES
1.
Boese CK, Centeno L, Walters RW. Blood conservation using tranexamic acid
is not superior to epsilon-aminocaproic acid after total knee arthroplasty. J Bone
Joint Surg Am. 2017;(99):1621-8.
2. Churchill JL, Toney VA, Truchan S, Anderson MJ. Using aminocaproic acid to
reduce blood loss after primary unilateral total knee arthroplasty. Am J Orthop
(Belle Mead NJ). 2016;(45):E245-8.
3.
Riaz O, Aqil A, Asmar S, Vanker R, Hahnel J, Brew C, et al. Epsilon-aminocaproic
acid versus tranexamic acid in total knee arthroplasty: a meta-analysis study.
J Orthop Traumatol. 2019;(20):28.
4.
Kim TK, Chang CB, Koh IJ. Practical issues for the use of tranexamic acid
in total knee arthroplasty: a systematic review. Knee Surg Sports Traumatol
Arthrosc. 2014;(22):1849-58.
5.
Camarasa MA, Ollé G, Serra-Prat M, Martín A, Sánchez M, Ricós P, et al. Efficacy
of aminocaproic, tranexamic acids in the control of bleeding during total knee
replacement: a randomized clinical trial. Br J Anaesth. 2006;(96):576-82.
6.
Churchill JL, Puca KE, Meyer E, Carleton M, Anderson MJ. Comparing
ε-aminocaproic acid and tranexamic acid in reducing postoperative transfusions
in total knee arthroplasty. J Knee Surg. 2017;(30):460-6.
7.
Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic
acid in total knee replacement: a systematic review and meta-analysis. J Bone
Joint Surg Br. 2011;(93):1577-85.
8.
Dai WL, Zhou AG, Zhang H, Zhang J. Most effective regimen of trane-
xamic acid for reducing bleeding and transfusions in primary total knee
arthroplasty: a meta-analysis of randomized controlled trials. J Knee Surg.
2018;(31):654-63.
9. Shin YS, Yoon JR, Lee HN, Park SH, Lee DH. Intravenous versus topical tra-
nexamic acid administration in primary total knee arthroplasty: a meta-analysis.
Knee Surg Sports Traumatol Arthrosc. 2017;(25):3585-95.
10.
Eriksson O, Kjellman H, Pilbrant A, Schannong M. Pharmacokinetics of tranexamic
acid after intravenous administration to normal volunteers. Eur J Clin Pharmacol.
1974;(7):375-80.
11. Nadeau RP, Howard JL, Naudie DD. Antifibrinolytic therapy for perioperative
blood conservation in lower-extremity primary total joint arthroplasty. JBJS Rev.
2015;(3):01874474-201503060-00005.
12. Guerreiro JPF, Lima DR, Bordignon G, Danieli MV, Queiroz AO, Cataneo DC.
Platelet-Rich Plasma (PRP) and Tranexamic Acid (TXA) applied in total knee
arthroplasty. Acta Ortop Bras. 2019;(27):248-51.
13.
Roy SP, Tanki UF, Dutta A, Jain SK, Nagi ON. Efficacy of intra-articular tranexamic
acid in blood loss reduction following primary unilateral total knee arthroplasty.
Knee Surg Sports Traumatol Arthrosc. 2012;(20):2494-501.
14. Serrano Mateo L, Goudarz Mehdikhani K, Cáceres L, Lee YY, Gonzalez Della
Valle A. Topical tranexamic acid may improve early functional outcomes of
primary total knee arthroplasty. J Arthroplasty. 2016;(31):1449-52.