You are on page 1of 4

Journal of Orthopaedic Surgery 2016;24(2):179-82

Topical tranexamic acid versus autotransfusion


after total knee arthroplasty
Yunus Guzel, Osman T Gurcan, Umut H Golge, Turan C Dulgeroglu, Hasan Metineren
Ordu University Medical School, Turkey

ABSTRACT
Purpose. To compare the use of topical tranexamic
acid (TXA) with postoperative autologous transfusion
(PAT) in terms of blood loss, need for allogeneic blood
transfusion, and cost-effectiveness.
Methods. Records of 25 men and 125 women (mean
age, 67 years) who underwent primary unilateral
total knee arthroplasty (TKA) and were randomised
to the PAT group (n=50), topical TXA group (n=50),
or routine drainage group (control) [n=50] were
reviewed. Pre- and post-operative haemoglobin level,
total postoperative drainage volume, and the need
for allogeneic blood transfusion were recorded.
Results. The 3 groups were comparable in terms of
age, gender, and preoperative haemoglobin level. The
total postoperative drainage volume was lower in the
TXA group than the PAT or routine drainage groups
(174.48 vs. 735 vs. 760 ml, p<0.001). The postoperative
haemoglobin level was lower in the routine drainage
group than the PAT or TXA groups on day 1 (11.67 vs.

12.33 vs. 12.40 g/dl, p<0.001) and day 3 (9.9 vs. 10.7
vs. 11.14 g/dl, p<0.001). The number of patients who
received allogeneic blood transfusion was higher
in the routine drainage group (12 and 4 patients
received 1 and 2 units of blood, respectively) than
the PAT group (4 patients received 1 unit of blood) or
the TXA group (none required transfusion) [p<0.001],
and the respective total transfusion cost was $1200,
$240, and $0. The total cost was lowest in the TXA
group followed by the routine drainage group and
PAT group ($200 vs. $1200 vs. $12 390). No patient
developed acute infection, deep venous thrombosis,
pulmonary embolism, myocardial infarction, or
stroke.
Conclusion. Compared with PAT, topical TXA
was more cost-effective and resulted in less total
postoperative drainage volume and less need for
allogeneic blood transfusion.
Key words: arthroplasty, replacement, knee; blood loss,
surgical; blood transfusion, autologous; hemostasis,
surgical; tranexamic acid

Address correspondence and reprint requests to: Yunus Guzel, Ordu University Medical School, Turkey. Email:
dryg@windowslive.com

Journal of Orthopaedic Surgery

180 Y Guzel et al.

INTRODUCTION
To reduce blood loss and the need for allogeneic blood
transfusion during total knee arthroplasty (TKA),
application of controlled hypotensive anaesthesia,
delayed drainage, tourniquet release before wound
closure, topical or systemic tranexamic acid (TXA),
and postoperative autologous transfusion (PAT)
has been advocated.115 TXA is an analogue of the
amino acid lysine. When administered systemically,
TXA competitively inhibits plasminogen activation
and plasmin binding to fibrin, thus inhibiting fibrin
degradation. When used topically, TXA acts directly
on microvasculature and clot stabilisation, thus
reducing local bleeding.47,14,15 PAT re-infuses blood
collected in the surgical drain into the patient and thus
reduces the need for allogeneic blood transfusion.813
This study compared the use of topical TXA with
PAT in terms of blood loss, need for allogeneic blood
transfusion, and cost-effectiveness.
MATERIALS AND METHODS
This study was approved by the ethics committee of
our hospital. Records of 176 patients who underwent
primary unilateral TKA between October 2013 and
November 2014 by a single team of surgeons with
standardised anaesthetic and surgical protocols
were reviewed. Of them, 26 patients with a history
of venous thromboembolism, preoperative use of
anticoagulants (acetylsalicylic acid, enoxaparin, or
any other oral or intravenous agent), obvious anaemia
or coagulopathy before surgery were excluded. The
remaining 25 men and 125 women (mean age, 67
years) were randomised to the PAT group (n=50),
topical TXA group (n=50), or routine drainage group
(control) [n=50].
Cemented TKA was performed through a
standard medial parapatellar approach with
tourniquet use under spinal or regional block or
general anaesthesia. A posterior cruciate ligamentpreserving prosthesis was used. The patellar surface
was not changed. An intramedullary guide was used
for femoral preparation, and an extramedullary guide
was used for tibial preparation. Thromboembolismdeterrent stockings and enoxaparin (40 mg before
surgery and continued daily for 10 days) were used
as venous thromboembolism prophylaxis.16
For the topical TXA group, a drain and injector
tip were placed within the joint before closing the
arthrotomy. The drain was clamped and 1.5 g TXA
(Transamine, FAKO, Istanbul, Turkey) diluted in
100 ml normal saline was injected intra-articularly

via the injector tip. The drain was released after one
hour.
For the PAT group, the CellTrans (SUMMIT,
Gloucestershire, UK) was used. A drain was inserted
into the knee joint at the end of TKA, and low suction
drainage was started 30 minutes later. More than 150
ml of blood had accumulated within 6 hours and was
re-infused into the patient. After that, the system was
used as a normal closed drain system.
For the controls, a low-suction drain was placed
in the knee joint and removed after 24 hours.
Blood transfusion was indicated when the
haemoglobin (Hb) level fell below 8 g/dl or the patient
was symptomatic of anaemia. The postoperative Hb
level was measured daily, and the lowest value was
used for analysis. Transfusion cost per 1 unit of red
blood cells was estimated to be $60 in 2014 at our
hospital; the cost of 1.5 g of TXA was approximately
$4 and the cost of PAT using the CellTrans system was
approximately $243 in 2014.1720
Doppler ultrasonography was used to detect
proximal or distal deep venous thrombosis.
Ventilation/perfusion scanning or spiral computed
tomography was used only when pulmonary
embolism was suspected clinically; this avoided
unnecessary exposure to radiation and additional
costs.
The normality of distribution of the continuous
variables was tested by the Kolmogorov-Smirnov test.
The ANOVA test was used for normally distributed
numerical variables (Hb level), whereas the KruskalWallis test was used for nonnormally distributed
numerical variables (drain volume). Sub-group
analyses were made using the Mann-Whitney U test.
Patients who did or did not receive allogeneic blood
transfusion were compared using the Chi-square
test. A value of p<0.05 was considered statistically
significant.
RESULTS
The 3 groups were comparable in terms of age,
gender, and preoperative haemoglobin level (Table).
The total postoperative drainage volume was lower
in the TXA group than the PAT or routine drainage
groups (174.48 vs. 735 vs. 760 ml, p<0.001). The
postoperative Hb level was lower in the routine
drainage group than the PAT or TXA groups on day
1 (11.67 vs. 12.33 vs. 12.40 g/dl, p<0.001) and day 3
(9.9 vs. 10.7 vs. 11.14 g/dl, p<0.001). The number of
patients who received allogeneic blood transfusion
was higher in the routine drainage group (12 and 4
patients received 1 and 2 units of blood, respectively)

Vol. 24 No. 2, August 2016

Topical tranexamic acid versus autotransfusion after TKA 181


Table
Patient characteristics and outcome*

Parameter

Topical tranexamic
acid group (n=50)

Age (years)
Male
Female
Haemoglobin level (g/dl)
Preop
Postop day 1
Postop day 3
Total drain output (ml)
Unit of allogeneic blood transfusion
Total transfusion cost (US$)
Total cost (US$)

Postoperative
autologous transfusion
group (n=50)

Routine drainage
group (n=50)

p Value

66.55.1
7 (14)
43 (86)

66.95.1
8 (16)
42 (84)

674.5
10 (20)
40 (80)

0.35
0.64
0.72

13.660.82
12.400.69
11.140.77
174.48128
0 (0)
0
200

13.80.65
12.330.67
10.70.85
735191.8
4 (8)
240
12 390

13.690.61
11.670.70
9.900.70
760145
20 (40)
1200
1200

0.527
<0.001
<0.001
<0.001
<0.001
-

* Data are presented as no. (%) or meanSD

than the PAT group (4 patients received 1 unit of


blood) or the TXA group (none required transfusion)
[40% vs. 8% vs. 0%, p<0.001], and the respective
total transfusion cost was $1200, $240, and $0. The
total cost was lowest in the TXA group followed by
the routine drainage group and PAT group ($200
vs. $1200 vs. $12390). No patient developed acute
infection, deep venous thrombosis, pulmonary
embolism, myocardial infarction, or stroke.
DISCUSSION
It is important to reduce blood loss during TKA in
elderly patients with limited cardiovascular function.
Tourniquet use is the most common method to
limit blood loss.21 Application of PAT and topical
or systemic TXA to achieve surgical haemostasis
without tourniquet use is increasingly popular.
Compared with routine drainage, PAT enabled
a higher postoperative Hb level and lower blood
loss, with the cost of PAT being $75 and the cost
of allogeneic blood transfusion (including crossmatching, delivery and refrigerated storage) being
$761.8 Another study reported the cost for one unit
of allogeneic blood transfusion as $787 and the cost
of TXA as $58.6 In a meta-analysis, the use of PAT
reduced the need for allogeneic blood transfusion
and decreased postoperative hospital costs.22 In our
study, TXA was cheaper, more accessible, and easier
to apply than PAT, although there was no significant

difference in postoperative Hb level between TXA


and PAT. Topical application of TXA is more or
equally effective compared with systemic use.5,23,24
The amount of systemic absorption of TXA following
topical application can be clinically disregarded.14
There is no evidence that topical or systemic
application of TXA is associated with an increased rate
of venous thromboembolism, myocardial infraction,
or stroke.48,2527 The dosage of topical TXA varies and
has been reported to be 3 g TXA/100 ml saline,5 1 g
TXA/10 ml saline,6 1.5 g TXA/50 ml saline,28 and 1.5
g and 3 g TXA/100 ml saline.14
This study had several limitations. It was
retrospective. Postoperative pain, wound healing,
and time to discharge were not evaluated. TKAs
were performed by 2 different surgeons, but the
anaesthetic and surgical protocols and prosthesis
were standardised.
CONCLUSION
Compared with PAT, topical TXA was more costeffective and resulted in less total postoperative
drainage volume and less need for allogeneic blood
transfusion.
DISCLOSURE
No conflicts of interest were declared by the authors.

182 Y Guzel et al.

Journal of Orthopaedic Surgery

REFERENCES
1. Sharrock NE, Mineo R, Urquhart B, Salvati EA. The effect of two levels of hypotension on intraoperative blood loss during
total hip arthroplasty performed under lumbar epidural anesthesia. Anesth Analg 1993;76:580-4.
2. Zhang Y, Li ZJ, Zheng YF, Feng SQ, Li H. Delayed drainage versus autotransfusion drainage and routine drainage after total
knee arthroplasty: a comparative study. J Orthop Surg Res 2013;8:39.
3. Zan PF, Yang Y, Fu D, Yu X, Li GD. Releasing of tourniquet before wound closure or not in total knee arthroplasty: a metaanalysis of randomized controlled trials. J Arthroplasty 2015;30:317.
4. Carvalho LH Jr, Frois Temponi E, Machado Soares LF, Gonalves MB, Paiva Costa L, Tavares de Souza ML. Bleeding reduction
after topical application of tranexamic acid together with Betadine solution in total knee arthroplasty. A randomised
controlled study. Orthop Traumatol Surg Res 2015;101:837.
5. Hamlin BR, DiGioia AM, Plakseychuk AY, Levison TJ. Topical versus intravenous tranexamic acid in total knee arthroplasty.
J Arthroplasty 2015;30:3846.
6. Tuttle JR, Ritterman SA, Cassidy DB, Anazonwu WA, Froehlich JA, Rubin LE. Cost benefit analysis of topical tranexamic acid
in primary total hip and knee arthroplasty. J Arthroplasty 2014;29:15125.
7. Wang H, Shen B, Zeng Y. Comparison of topical versus intravenous tranexamic acid in primary total knee arthroplasty: a
meta-analysis of randomized controlled and prospective cohort trials. Knee 2014;21:98793.
8. Horstmann W, Kuipers B, Ohanis D, Slappendel R, Kollen B, Verheyen C. Autologous re-transfusion drain compared with
no drain in total knee arthroplasty: a randomised controlled trial. Blood Transfus 2014;12(1 Suppl):S17681.
9. Horstmann WG, Kuipers BM, Slappendel R, Castelein RM, Kollen BJ, Verheyen CC. Postoperative autologous blood
transfusion drain or no drain in primary total hip arthroplasty? A randomised controlled trial. Int Orthop 2012;36:20339.
10. Li N, Li P, Liu M, Wang D, Xia L. Comparison between autologous blood transfusion drainage and no drainage/closedsuction drainage in primary total hip arthroplasty: a meta-analysis. Arch Orthop Trauma Surg 2014;134:162331.
11. Tsumara N, Yoshiya S, Chin T, Shiba R, Kohso K, Doita M. A prospective comparison of clamping the drain or post-operative
salvage of blood in reducing blood loss after total knee arthroplasty. J Bone Joint Surg Br 2006;88:4953.
12. Friederichs MG, Mariani EM, Bourne MH. Perioperative blood salvage as an alternative to predonating blood for primary
total knee and hip arthroplasty. J Arthroplasty 2002;17:298303.
13. So-Osman C, Nelissen RG, Eikenboom HC, Brand A. Efficacy, safety and user-friendliness of two devices for postoperative
autologous shed red blood cell re-infusion in elective orthopaedic surgery patients: a randomized pilot study. Transfus Med
2006;16:3218.
14. Wong J, Abrishami A, El Beheiry H, Mahomed NN, Roderick Davey J, Gandhi R, et al. Topical application of tranexamic
acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am
2010;92:250313.
15. Jang B, Kao M, Bohm MT, Harris IA, Chen DB, MacDessi SJ. Intra-articular injection of tranexamic acid to reduce blood
loss after total knee arthroplasty. J Orthop Surg (Hong Kong) 2014;22:1469.
16. Fitzgerald RH Jr, Spiro TE, Trowbridge AA, Gardiner GA Jr, Whitsett TL, OConnell MB, et al. Prevention of venous
thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group
comparison of enoxaparin and warfarin. J Bone Joint Surg Am 2001;83:9006.
17. Oge T, Kilic CH, Kilic GS. Economic impact of blood transfusions: balancing cost and benefits. Eurasian J Med 2014;46:47
9.
18. Choufani C, Barbier O, Bajard X, Ollat D, Versier G. Medical and economic impact of a haemostatic sealant on the rate of
transfusion after total knee arthroplasty [in French]. Transfus Clin Biol 2015;22:229.
19. Krebs VE, Higuera C, Barsoum WK, Helfand R. Blood management in joint replacement surgery: whats in and whats out.
Orthopedics 2006;29:8013.
20. Sehat KR, Evans RL, Newman JH. Hidden blood loss following hip and knee arthroplasty. Correct management of blood
loss should take hidden loss into account. J Bone Joint Surg Br 2004;86:5615.
21. Harsten A, Bandholm T, Kehlet H, Toksvig-Larsen S. Tourniquet versus no tourniquet on knee-extension strength early after
fast-track total knee arthroplasty: a randomized controlled trial. Knee 2015;22:12630.
22. Haien Z, Yong J, Baoan M, Mingjun G, Qingyu F. Post-operative auto-transfusion in total hip or knee arthroplasty: a metaanalysis of randomized controlled trials. PLoS One 2013;8:e55073.
23. 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;93:157785.
24. Seo JG, Moon YW, Park SH, Kim SM, Ko KR. The comparative efficacies of intra-articular and IV tranexamic acid for
reducing blood loss during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 2013;21:186974.
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 2013;471:1504.
26. Panteli M, Papakostidis C, Dahabreh Z, Giannoudis PV. Topical tranexamic acid in total knee replacement: a systematic
review and meta-analysis. Knee 2013;20:3009.
27. Tan J, Chen H, Liu Q, Chen C, Huang W. A meta-analysis of the effectiveness and safety of using tranexamic acid in primary
unilateral total knee arthroplasty. J Surg Res 2013;184:8807.
28. Tahmasebi MN, Bashti K, Ghorbani G, Sobhan MR. Intraarticular administration of tranexamic acid following total knee
arthroplasty: a case-control study. Arch Bone Jt Surg 2014;2:1415.