Open Journal of Orthopedics, 2013, 3, 249-252 Published Online October 2013 ( 249
Does Pre-Operative Tranexamic Acid Increase the
Incidence of Thromboembolism in Primary Lower Limb
Veenesh Selvaratnam*, James R. Fountain, Nigel J. Donnachie, Thomas G. Thomas, Fintan A. Carroll
Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UK.
Email: *
Received July 11th, 2013; revised August 15th, 2013; accepted September 1st, 2013
Copyright © 2013 Veenesh Selvaratnam et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction: Tranexamic Acid (TA) has been shown to decrease peri-operative bleeding in primary lower limb ar-
throplasty surgery. There are still concerns with reg ards to the increased risk of thromboembolic events with the use o f
TA. The aim of this study was to assess whether the use of pre-operative TA increased the incidence of Deep Vein
Thrombosis (DVT) and Pulmonary Embolism (PE) in Total Hip Replacement (THR) and Total Knee Replacement
(TKR). Methods: Patients who underwent primary THR or TKR between August 2007 and August 2009 were identi-
fied from the databases of three surgeons within the lower limb arthroplasty unit. A retrospective case notes analysis
was performed. DVT was diagnosed on Duplex Ultrasound Scan and PE on CT Pulmonary Angiogram. A positive re-
sult was a diagnosis of DVT or PE within 3 months of surgery. Results: 701 patients underwent pr imary THR an d TKR
over the 2-year period. 320 patients (189 THR, 131 TKR) received TA pre-operatively. 381 patients (190 THR, 191
TKR) did not receive TA prior to surgery. A total of 8 (2.5%) patients who received TA were diagnosed with either a
DVT (4) or PE (4) post operatively. In those patients not receiving TA, 6 had a DVT and 4 had a PE, a total of 10
(2.6%). Conclusion: Pre-operative use of Tranexamic Acid in primary THR and TKR does not increase the incidence
of DVT and PE.
Keywords: Tranexamic Acid; DVT; PE; TKR; THR
1. Introduction
Post operative anaemia following lower limb arthroplasty
delays rehabilitation and discharge with the increased
complications and costs associated with an extended in-
patient stay. A variety of blood conserving techniques
have been developed to reduce blood loss and post-op-
erative transfusion rates. Th ese include autologous blood
transfusion, intra-operative blood salvage, controlled hy-
potension and the use of erythropoietin and antifibrino-
lytic agents.
Antifibrinolytics currently include aprotinin and tra-
nexamic acid (TA). TA is an analogue of the amino acid
lysine. It inhibits fibrinolysis by blocking the lysine bin-
ding sites of plasminogen [1,2] reducing the conversion
of plasminogen to plasmin. The enzyme plasmin is res-
ponsible for the degradation of fibrin clot, fibrinogen and
other plasma proteins including the procoagulant factors
V and VIII. Together these form the ba sic framework for
the formation of a blood clot in heamostasis. At higher
doses, TA can directly inhibit plasmin rather than pre-
venting its formation.
TA has been used in urological, gynaecological and
cardiothoracic surgery to reduce blood loss and has been
shown to decrease peri-operative bleeding in primary lo-
wer limb arthroplasty surgery [2-9]. There are still con-
cerns with regards to the increased risk of thromboembo-
lic events with the use of TA in the clinical setting. Al-
though TA may dramatically reduce blood loss [10] it
has yet to gain widespread acceptance amongst those per-
forming lower limb arthroplasties. The aim of this study
was to assess whether the use of pre-operative TA increa-
sed the incidence of Deep Vein Thrombosis (DVT) and
Pulmonary Embolism (PE) in Total Hip Replacement
(THR) and Total Knee Replacement (TKR).
2. Materials and Methods
The local audit department approval was obtained. Pa-
*Corresponding a uthor.
Copyright © 2013 SciRes. OJO
Does Pre-Operative Tranexamic Acid Increase the Incidence of Thromboembolism in Primary Lower
Limb Arthroplasty?
tients who underwent primary THR or TKR between Au-
gust 2007 and August 2009 were identified from the da-
tabases of three surgeons within the lower limb arthro-
plasty unit.
The criteria for inclusion in this stud y were:
1) patient s who underwent pr i mary TKR or THR
2) a diagnosis of osteoarthritis, rheumatoid arthritis
and aseptic bone necrosis
3) no prior history of venous thromboembolic (VTE)
4) no history of bleedi ng disorder
5) not on any prior anticoagulant
A retrospective case notes analysis was performed
comparing patients who received TA and those who did
not receive TA during TKR and THR.
The dose of TA used was a single bolus dose of 10
mg/kg body weight given intravenously 30 minutes prior
to anaesthetic induction. TA given intravenously diffuses
rapidly into synovial fluid and membrane [11] and maxi-
mum plasma levels are reached in 5 to 15 minutes. The
haemostatic effect of TA has been shown to be most ef-
fective when administered prior to the operation allowing
suppression of fibrinolysis from the start of surgery [10].
All patients had the same pre and peri-operative care
and were followed up post operatively at 6 weeks, 6
months and then yearly.
In accordance with the NICE guidelines, all our pa-
tients who underwent THR had the appropriate chemical
VTE prophylaxis during their inpatient stay. Full leg gra-
duated compression elastic stockings were worn postope-
ratively by all patients until fu lly mobile. Chemical VTE
prophylaxis was started six hours after surgical closure in
all patients provided haemostasis had been established.
At the time all patients received thromboprophylaxis with
a low molecular weight heparin for 14 days and 28 days
post operatively for TKR and THR respectively.
Following clinical examination of a symptomatic pa-
tient, DVT was diagnosed on duplex ultrasound scan and
PE on CT pulmonary angiography (CTPA). A positive
result was a diagnosis of DVT or PE within 3 months of
3. Results
A total of 701 patients underwent lower limb arthroplasty
over the two year period, with 379 patients having pri-
mary THR and 322 patients receiving a TKR.
The 379 patients undergoing primary THR had an age
range from 54 - 88 years (median: 72 years). 189 patients
received TA pre-operatively. 190 patients did not receive
TA prior to surgery. A total of 4 (2.1%) patients who re-
ceived TA were diagnosed with either a DVT (2) or PE
(2) post operatively. One patient had a below knee DVT
while the other had an above knee DVT. In those patients
not receiving TA, 2 patients had a PE (1.1%). This is sta-
tistically not significant p = 0.184.
322 patients underwent primary TKR over the 2 year
period. Their age range was from 55 - 90 years (median:
74 years). 131 patients received TA pre-operatively. 191
patients did not receive TA prior to surgery. A total of 4
(3.1%) patients who received TA were diagnosed with a
thromboembolic even t post-operatively. 2 with DVT an d
2 with a PE. Both patient had a below knee DVT. In
those patients not receiving TA, 6 had a DVT and 2 had a
PE, a total of 8 (4.2%). Three had an above knee DVT
while the other three had an above knee DVT. Patients of
both groups with post operative venous thromboembolic
(VTE) disease were anticoagulated with warfarin (3
months for DVT and 6 months for PE).
None of the patients in our study died as a direct result
of VTE and there were no adverse reactions to TA in all
4. Discussion
A higher haemoglobin following lower limb arthroplasty
has been associated with a significantly shorter length of
stay for inpatient rehabilitation and improved patient
function score [12].
VTE is a relatively common, occasionally fatal and
costly complication of elective TKR and THR surgery.
The reported prevalence of DVT in patients not receiving
prophylaxis in clinical trials using mandatory venogra-
phy has been 45% - 57% after THR [13] and 40% - 84%
after TKR [14]. The reported prevalence of PE in other
trials has been 0.7% - 30% [15] after THR (fatal PE 0.1%
- 0.4%), and 1.8% - 7% after TKR (fatal PE 0.2% - 0.7%)
This risk of VTE in lower limb arthroplasty surgery is
theoretically increased with the use of antifibrinolytic
agents such as TA but it would seem the effect of TA is
more pronounced in operative wounds than in the peri-
pheral venous blood [4]. The reduced thrombogenic ef-
fect in the peripheral venous system is potentially be-
cause the fibrinolytic activity in v ein walls is not affected
by TA.
The therapeutic level of TA is between 5 - 10 mg/l
[17]. A pre-oper ative IV dose of 10 mg/kg of TA gives a
plasma level of approximately 10 mg/l and therefore a
therapeutic concentration for the period of hyperfibrino-
lysis associated with the peri-operative period of arthro-
plasty surgery [7]. TA was first introduced in arthropla-
sty surgery in order to reduce peri-operative blood loss
and it has been proven to do that effectively. Post-opera-
tive blood loss is maximal in the first eight hours [18]
and it has been shown subsequently that a single dose of
TA is enough to cover this immediate post-operative pe-
riod [19]. Other authors would argue the need for further
Copyright © 2013 SciRes. OJO
Does Pre-Operative Tranexamic Acid Increase the Incidence of Thromboembolism in Primary Lower
Limb Arthroplasty? 251
post operative doses but with a therapeutic plasma con-
centration of 5 mg/l still present at 18 hours after a dose
of 10 mg/kg [17] we feel a single dose is adequate.
A single pre-operative bolus dose at induction has been
used in other studies [8] while other trials have combined
a pre-operative dose with intra-operative infusions or fur-
ther post operative doses [7,20].
Ralley used one 20 mg/kg dose of TA before skin in-
cision for THA or 10 minutes before tourniquet release in
TKA [8] while Orpen used 15 mg/kg of TA given IV at
the start of cement mixing in TKA [7].
Sukeik et al. [21] analysed 11 randomised controlled
trials with pre-operative doses that ranged from 10 mg/kg
to 30 mg/kg, the biggest proportion only using a single
bolus pre- operativel y .
The use of LMWH thromboprophylaxis for all our pa-
tients follows NICE guidance and is in keeping with Su-
deik’s [21] meta-analysis in which the majority of trials
used LMWH as chemical DVT prophylaxis.
Only patients who had a clinical DVT on examination
were investigated with a duplex ultrasound Scan. Clini-
cally suspected PE was investigated with CT Pulmonary
Angiography (CTPA). Dup lex ultrasound scan has a sen-
sitivity of 97% and a specificity of 98% for the d iagnosis
of DVT [22] while CTPA remains the gold standard for
the diagnosis of PE [23].
Our results have confirmed the VTE findings in other
published data. Tanaka et al. found no difference in DVTs
between a group receiving TA and their control [10]. Lo-
zano et al. [9] studying the effectiveness and safety of
TA reported on 414 p ts who had been examined clinical-
ly and by contrast venography. They showed a lower fre-
quency of clinically evident thromboembolic complica-
tions in the cohort treated with TA compared to those
Sudeik et al. found no significant differences in DVT
or PE among the randomized controlled trials included in
the meta-analysis. All studies had patients in the inter-
vention group receiving IV TA and a control group recei-
ving placebo, another antifibrinolytic or no treatment
[21]. 9 out of the 11 trials used clinical evaluation as a
screen for DVT in symptomatic post operative patien ts in
keeping with our protocols for further investigation.
Orpen et al. used duplex ultrasound as an assessment
of the proximal deep venous system for DVT on all pa-
tients five days post TKA in their prospective trial of TA.
No patient developed clinical signs or symptoms of DVT
and there was no evidence of thromboembolism on du-
plex perfor med [7].
Benoni had 4 (9.3%) confirmed DVTs in 43 TKR pa-
tients treated with TA compared with 3 (7%) DVTs and
1 PE in their placebo group of the same number [2]. Al-
though a higher percentage of VTE events the difference
between the prophylactic and placebo groups remains
5. Conclusion
In summary, our report shows that the use of pre-ope-
rative tranexamic acid in primary total knee and hip re-
placement does not increase the incidence of DVT and
PE. TA can be integrated easily into routin e practice and
it would appear that the beneficial effects of reduced blood
loss, reduced transfusion requ irements and increased hae-
moglobin levels at discharge are not accompanied with
an increase in thromboembolic complications.
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Limb Arthroplasty?
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