Comparison of outcomes between intra-articular tranexamic acid versus intravenous tranexamic acid in unilateral knee joint replacement

Abstract

Background: The goal of this research was to assess the effectiveness and safety of intra-articular tranexamic acid (TA) with intravenous (IV) TA in reducing perioperative blood loss, the severity of early postoperative problems, and venous thromboembolism in patients who have had a primary unilateral cemented total knee replacement. Patients and methods: This comparative study was undertaken using a non-probability purposive sampling technique at the A total of number 71 patients, aged 35 to 75 years, who underwent unilateral cemented total knee replacement for advanced knee osteoarthritis were included in the study. Patients who had known allergic reactions to tranexamic acid, risk factors of thromboembolism, severe kidney and heart diseases, and blood clotting disorders were excluded. The patients were divided into two groups, A and B. Pre-operatively, patients in Group A were given intraarticular tranexamic acid (3000mg). In Group B, intravenous tranexamic acid (10mg/kg) was given pre-operatively. Outcome parameters studied were drained blood (DB), level of hemoglobin (Hb), blood transfusion (BT), and hematocrit (Hct) after 48 hours of surgery and compared with the preoperative value. Data was entered and analyzed using SPSS version 21.0. Independent sample T-test was applied to compare the hematocrit and hemoglobin difference in the two groups, and the P-value was taken less than 0.05 as significant. Results: Out of the total 36 patients in Group A, there were 20 (55.5%) males and 16 (44.4%) females, while amongst 35 patients in Group B, there were 21 (60%) males and 14 (40%) females. The mean preoperative Haemoglobin (Hb) in Group A was 13.9+1.2 and 13.8+0.9 in Group B (p = 0.44). The mean postoperative Hb in Group A was 12.11±2.47 and 11.24 ± 3.52 in Group B (p = 0.002). The mean variation of Hct in Group A was 4.49 and 6.82 in Group B (p = 0.001). Conclusion: Intra-articular tranexamic acid during total knee joint replacement is a viable alternative to the established intravenous tranexamic acid with statistically significant high postoperative hemoglobin and hematocrit levels.

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© 2021 Authors J Fatima Jinnah Med Univ 2021; 15: 76-80
Original article
Comparison of outcomes between intra-articular tranexamic
acid versus intravenous tranexamic acid in unilateral knee joint
replacement
Mumraiz Naqshaband1, Muhammad Taqi2, Sohail Ashraf3, Faisal Masood4, Muhammad Akhtar5, Muhammad
Jazib Nadeem6, Javaid Hassan Raza7, Rana Dilawaz Nadeem8
1Assistant Professor, Department of Orthopedic Surgery, King Edward Medical University / Mayo Hospital, Lahore. 2PGR, Department of
Orthopedic Surgery, King Edward Medical University / Mayo Hospital, Lahore. 3Senior Registrar, Mayo Hospital, Lahore. 4Associate Professor,
Department of Orthopedic Surgery, Mayo Hospital, Lahore. 5Associate Professor, Department of Orthopedic Surgery, Mayo Hospital, Lahore.
6Research Assistant, Department of Orthopedic Surgery, Mayo Hospital, Lahore. 7Research Assistant, Department of Orthopedic Surgery, Mayo
Hospital, Lahore. 8Professor, Department of Orthopedic Surgery, King Edward Medical University / Mayo Hospital, Lahore.
Correspondence to:
Dr. Muhammad Taqi, Email: dr.taqi227@gmail.com
ABSTRACT
Background: The goal of this research was to assess the effectiveness and safety of intra-articular tranexamic acid (TA)
with intravenous (IV) TA in reducing perioperative blood loss, the severity of early postoperative problems, and venous
thromboembolism in patients who have had a primary unilateral cemented total knee replacement.
Patients and methods: This comparative study was undertaken using a non-probability purposive sampling
technique at the Department of Orthopedic Surgery, King Edward Medical University / Mayo Hospital,
Lahore, from July 1st, 2018 to October 30th, 2019. A total of number 71 patients, aged 35 to 75 years, who
underwent unilateral cemented total knee replacement for advanced knee osteoarthritis were included in the study.
Patients who had known allergic reactions to tranexamic acid, risk factors of thromboembolism, severe kidney and
heart diseases, and blood clotting disorders were excluded. The patients were divided into two groups, A and B. Pre-
operatively, patients in Group A were given intraarticular tranexamic acid (3000mg). In Group B, intravenous
tranexamic acid (10mg/kg) was given pre-operatively. Outcome parameters studied were drained blood (DB), level of
hemoglobin (Hb), blood transfusion (BT), and hematocrit (Hct) after 48 hours of surgery and compared with the
preoperative value. Data was entered and analyzed using SPSS version 21.0. Independent sample T-test was applied to
compare the hematocrit and hemoglobin difference in the two groups, and the P-value was taken less than 0.05 as
significant.
Results: Out of the total 36 patients in Group A, there were 20 (55.5%) males and 16 (44.4%) females, while amongst
35 patients in Group B, there were 21 (60%) males and 14 (40%) females. The mean preoperative Haemoglobin (Hb)
in Group A was 13.9+1.2 and 13.8+0.9 in Group B (p = 0.44). The mean postoperative Hb in Group A was 12.11±2.47
and 11.24 ± 3.52 in Group B (p = 0.002). The mean variation of Hct in Group A was 4.49 and 6.82 in Group B (p =
0.001).
Conclusion: Intra-articular tranexamic acid during total knee joint replacement is a viable alternative to the established
intravenous tranexamic acid with statistically significant high postoperative hemoglobin and hematocrit levels.
Keywords:
Intra-articular tranexamic acid, Intravenous tranexamic acid, Knee arthroplasty, Effectiveness
INTRODUCTION
Total knee replacement surgery is related to a
significant amount of blood loss. Noticewala et al.
conducted cohort research with 104 males (16%) and
540 women (84 percent). The average age was 67.6
years and 10.1 years (18-94 years), respectively. The
results showed that 11% of the patients operated on for
unilateral total knee replacement require subsequent
blood transfusions.1,2 This increases the risk
Conflict of interest: The authors declared no conflict of interest exists.
Citation: Naqshaband M, Masood F, Taqi M, Ashraf S, Akhtar M, Nadeem
MJ, et al. Comparison of outcomes between intra-articular tranexamic acid
versus intravenous tranexamic acid in unilateral knee joint replacement. J
Fatima Jinnah Med Univ. 2021; 15(2):76-80.
DOI: https://doi.org/10.37018/EXBO5236
of blood transfusion-related complications such as the
transmission of infection, fluid overload, and blood
reactions.3 Different methods to decrease the need for
blood transfusion have been described, which include
injection of erythropoietin before the operation, use of
iron supplements, intraoperative use of tourniquet,
plasma rich concentrate, fibrin glue, and
pharmacological agents that act as antifibrinolytic
(tranexamic acid) used intraoperatively to decrease
blood loss.4 Tranexamic acid (TXA), which works as an
inhibitor of fibrinogen activity of plasma was first
described in 1995 for use intraoperatively in controlling
bleeding in primary total knee replacement.5,6 Since
then, many clinical trials have been done to assess the
effectiveness of tranexamic acid.6,7 There is a known

Naqshaband et al 77
increased risk of a thromboembolic event when used
intravenously in patients with chronic renal failure and
those with known previous ischaemic events and heart
disease.8
Intra-articular (IA) administration provides a
maximum concentration at the bleeding site with
limited systemic influence.9 A consensus regarding the
optimal route of administration of tranexamic acid to
control bleeding intraoperatively, with the least
complications, is still debated. This study aims to assess
the effectiveness of intraarticular use of tranexamic acid
to the established intravenous route in the control of
bleeding postoperatively and reduction of
thromboembolic complications in primary unilateral
total knee replacements.10
PATIENTS AND METHODS
This comparative study was undertaken using a
non-probability purposive sampling technique at
the Department of Orthopedic Surgery, King
Edward Medical University\Mayo Hospital,
Lahore, from July 1st, 2018, to October 30th, 2019.
The sample size was 71 cases. Patients aged 35 to
75 years with advanced knee osteoarthritis who
underwent unilateral cemented total knee replacement
were included. Patients who had known allergic
reactions to tranexamic acid, risk factors of
thromboembolism, severe kidney and heart diseases,
and blood clotting disorders were excluded. Ethical
approval was taken from the hospital ethical review
board. The patients were enrolled in the study after a
thorough informed consent process, with the purpose of
the study explained to them. The patients were
randomized into Group A and Group B with binary
envelope allocation. Four senior surgeons performed
the procedures in a standardized manner. Pre-
operatively, Patients in Group-A were given
intraarticular tranexamic acid 3000 mg in 50 ml of
normal saline after cementing.
After 10 minutes of drug administration, the wound was
closed without further flushing. While in Group B,
Intravenous tranexamic acid 10 mg per kg 20 was given
before the skin incision and repeated during the wound
closure. All patients received the same protocol for
every patient.11-14 All operations were performed under
spinal anesthesia using a midline skin incision with a
medial parapatellar approach. Tourniquets were used
only for a short time while cementing, intramedullary
jig used for femoral cuts, and extramedullary jig for
tibial cut used. Active drain placed in all patients for
first 48 hours of operation and antibiotics prophylaxis
along with thromboembolic prophylaxis by low
molecular weight heparin (1mg/kg) subcutaneously 12
hours after total knee replacements were given in all
patients for 14 days. The characteristics of the
individual group were based on body mass index, mean
age of patients, male to female ratio, preoperative
hemoglobin, American society of anesthesia grades
(ASA), and hematocrit level. Parameters studied were
the amount of drained blood, level of hemoglobin, and
hematocrit after 48 hours of surgery and compared with
preoperative value. The need for blood transfusion was
determined according to an institutional policy of
hemoglobin levels below 8g/dl. The Doppler scan for
deep vein thrombosis was done in symptomatic patients
(Calf pain & Lower limb swelling). Complete blood
count (CBC) was also measured on the 2nd day after the
operation of primary total knee replacements. 12 hours
after no addition, drains were removed, and patients
were discharged. Patients were called for follow-up at
14 days, 42 days, and 56 days. Data was entered and
analyzed using SPSS version 21.0. Independent sample
T-test was applied to compare the hematocrit and
hemoglobin difference in the two groups, and the p-
value was taken less than 0.05 as significant.
RESULTS
Out of the total 36 patients in Group A, there were 20
(55.5%) males and 16 (44.4%) females, while amongst
Table 1. Demographics of the patients
Demographics
Group A
(n=36)
Group B
(n= 35)
p-value
Age (years)
55±6.2
52.9±6.7
0.07
Gender
0.06
Male
20
16
Female
21
14
Body mass index
31.1+4.7
31.9+4.7
0.3
ASA grade scale
2.5+0.6
2.3+0.5
0.06
Preoperative hemoglobin Hb
13.9+1.2
13.8+0.9
0.44
Preoperative hematocrit Hct
39.94
40.21
0.698
Limb side
Right
24
25
0.06
Left
12
10

78 Comparison of outcomes between intra-articular tranexamic acid versus intravenous tranexamic acid in unilateral knee joint replacement
© 2021 Authors J Fatima Jinnah Med Univ 2021; 15: 76-80
Table 2. Postoperative comparison after total knee joint replacement
Postoperative
Group A
Group B
p-value
Haemoglobin mean (grams)
12.11±2.47
11.24±3.52
0.002
Hematocrit (Hct)
34.37±3.1
32.59±2.2
0.002
Average time minutes
92.5±13.7
96.69±12.3
0.05
Average blood loss millimeters
210 ± 20
250.65±24.5
0.05
Deep vein thrombosis
00
04
0.05
35 patients in Group B, there were 21 (60%) males and
14 (40%) females. The mean age of the patient in
Group A was 55±6.2 years and 52.9±6.7 years in
Group B. Left-sided total knee joint replacement was
done in 40 (56.3%) patients and 31 (44.3%) had a right-
sided total knee joint replacement. The mean operative
time of surgery in Group A was 92.5±13.7 minutes, and
in Group B was 96.69±12.3 minutes (p-value 0.06). A
210 ± 20ml blood loss was calculated in Group A
through drainage bottle, and in Group B, blood loss was
250.65±24.5 ml (Table 1). Group A's mean preoperative
Hemoglobin (Hb) was 13.9+1.2 and 13.8+0.9 in Group
B (p = 0.44). The mean postoperative Hb in Group A
was 12.11±2.47 and 11.24 ± 3.52 in Group B
(p = 0.002). The mean preoperative Hematocrit (Hct)
in Group A was 39.94 and 40.21 in Group B
(p = 0.698). The mean postoperative Hct in Group 1
was 34.37 and 32.59 in Group 2 (p = 0.003). The mean
variation of Hct in Group A was 4.49 and 6.82 in Group
B (p = 0.001) (Table 2). The mean numbers of blood
transfusions in Group A were two blood transfusions in
2 patients compared to five blood transfusions in 4
patients in Group B. We observed no complications at
follow-up of 2 weeks in Group A, while four cases of
deep vein thrombosis were developed in Group B.
These patients were treated with oral anticoagulants.
No case of venous thromboembolism was noted in
Group A. While comparing groups in terms of mean
age, body mass index, preoperative Hct/Hb, American
Society of Anesthesiologists grade (ASA) grade, there
were no statistical differences.
DISCUSSION
Several studies have investigated the role of tranexamic
acid in reducing blood loss and improving Hb in
patients undergoing orthopedic surgeries like total knee
replacement (TKR), total hip joint replacement (THR),
and spine surgeries, but the definitive efficacy has not
yet been documented.15,16 Fibrinolysis is increased after
surgical trauma, therefore increasing intraoperative and
postoperative blood loss. Tranexamic acid inhibits
fibrinolysis and thus decreases blood loss. The half-life
of tranexamic acid is 3 hours and 90 percent excreted by
the kidney in 24 hours. In a recent meta-analysis,
intraoperative blood loss decreased while performing
total knee replacements using intravenous tranexamic
acid, without complications thromboembolic events and
infection.17 In patients with chronic renal failure,
cardiac failure, myocardial infarction, history of
thromboembolism, neurovascular disorders, and
hormone replacement therapy, the chances of
thromboembolisms are high while using intravenous
tranexamic acid.18 One study on 1880 patients reported
24 (3.3%) patients developed symptomatic venous
thromboembolism, 16 (2.2%) deep vein thrombosis
(DVT), and 8 (1.1%) pulmonary embolism (PE).19
Current study observed four cases out of 35 (11.4%)
developed deep vein thrombosis in the intra-venous
tranexamic acid Group, and no case was seen in the
intra-articular group.
Administration of tranexamic acid intraarticular by
flushing the wound or by injection through a suction
drain after the closure of the wound will lead to a
decrease in the complication associated with
intravenous use of tranexamic acid. Previous meta-
analyses reported decreased blood loss using
intraarticular tranexamic acid in total knee replacements
without any complications of thromboembolism.20 In
this study, a reduced number of blood transfusions (2
blood) in the intra-articular tranexamic acid was
observed in the group compared to five blood
transfusions in 4 patients in the intravenous group.
While doing total knee replacements, the efficiency of
tranexamic acid to control blood losses is not well
established. Conflicting conclusions in different studies
while comparing intraarticular and intravenous
tranexamic acid results to control bleedings. Previous
studies report that the results of intraarticular
tranexamic acid are superior to intravenous tranexamic
acid.21 Sarazeema found a decreased incidence of blood
transfusion in patients with intravenous tranexamic
acid, relatively high blood transfusion requirements of
50 percent in patients who have not received any form
of tranexamic acid.22 The need for blood transfusions in
patients with total knee replacements is 11% to
69%.23,24. Li et al. reported that the intravenous
tranexamic acid group showed a greater postoperative
hemoglobin drop than the IA group.25 Similarly, in the
current study, the mean variation of Hct in the intra-
articular group was 4.49 and 6.82 in the intra-venous

Naqshaband et al 79
tranexamic acid group (p = 0.001). In contrast to the
above studies, in a review of six randomized controlled
and meta-analysis studies in total knee replacements
compared results in terms of intraoperative blood losses
and number of blood transfusions, the authors did not
find any difference between blood transfusions and
thromboembolic complications to compare results of
intraarticular and intravenous tranexamic acid.26
Some discrepancies exist between intravenous and
intraarticular administration of tranexamic acid while
considering some factors like intramedullary and
extramedullary jigs for resections of bone, indications
for blood transfusions, use of tourniquets either
incomplete procedure or while cementing only, and use
of drains. But in our institute, we used a tourniquet
before starting the procedure. Operative time in
patients with local intraarticular tranexamic acid is
approximately 10 minutes more because of a wait after
injection intraarticular, but it is without increasing
morbidity and has no statistical difference.
There were some limitations in this study related
to the small sample size, type of study, and the number
of surgeons who operated; four surgeons operated on
these patients, all were well experience but with
different surgical skills and operative times. In the
future, further prospective large cohort and randomized
studies are required for providing definitive evidence
about the route of tranexamic acid administration in
total knee joint arthroplasty.
CONCLUSION
This study showed that during total knee joint
replacement, intra-articular tranexamic acid has high
postoperative hemoglobin and hematocrit as compared
to the intravenous tranexamic acid group without any
increase in thromboembolism. The intra-articular dose
of 3 g of TXA was more efficacious than one-dose (10
mg/kg) IV injection in reducing drained blood loss. We
propose that the intra-articular route may be considered
in patients at increased risk of thromboembolism or in
whom intravenous tranexamic acid is relatively
contraindicated, e.g., renal impairment.
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