Does Pre-Operative Tranexamic Acid Increase the Incidence of Thromboembolism in Primary Lower Limb Arthroplasty?

doi:10.4236/ojo.2013.36046

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Open Journal of Orthopedics, 2013, 3, 249-252

http://dx.doi.org/10.4236/ojo.2013.36046 Published Online October 2013 (http://www.scirp.org/journal/ojo) 249

Does Pre-Operative Tranexamic Acid Increase the

Incidence of Thromboembolism in Primary Lower Limb

Arthroplasty?

Veenesh Selvaratnam*, James R. Fountain, Nigel J. Donnachie, Thomas G. Thomas, Fintan A. Carroll

Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UK.

Email: *[email protected]

Received July 11th, 2013; revised August 15th, 2013; accepted September 1st, 2013

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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.

Does Pre-Operative Tranexamic Acid Increase the Incidence of Thromboembolism in Primary Lower

Limb Arthroplasty?

250

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)

disease

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

surgery.

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

patients.

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%)

[16].

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

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

without.

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

nonsignificant.

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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