Eur J Anaesthesiol 2018; 35:116–122

GUIDELINES

European guidelines on perioperative venous

thromboembolism prophylaxis
Surgery in the elderly
Sibylle Kozek-Langenecker, Christian Fenger-Eriksen, Emmanuel Thienpont and
Giedrius Barauskas, for the ESA VTE Guidelines Task Force

The risk for postoperative venous thromboembolism (VTE) is therapy) and correction if present (e.g. anaemia, coagulo-
increased in patients aged more than 70 years and in elderly pathy) (Grade 2C). We suggest against bilateral knee
patients presenting with co-morbidities, for example cardio- replacement in elderly and frail patients (Grade 2C). We
vascular disorders, malignancy or renal insufficiency. There- suggest timing and dosing of pharmacological VTE prophy-
fore, risk stratification, correction of modifiable risks and laxis as in the non-aged population (Grade 2C). In elderly
sustained perioperative thromboprophylaxis are essential patients with renal failure, low-dose unfractionated heparin
in this patient population. Timing and dosing of pharmaco- (UFH) may be used or weight-adjusted dosing of low molec-
prophylaxis may be adopted from the non-aged population. ular weight heparin (Grade 2C). In the elderly, we recom-
Direct oral anti-coagulants are effective and well tolerated in mend careful prescription of postoperative VTE prophylaxis
the elderly; statins may not replace pharmacological throm- and early postoperative mobilisation (Grade 1C). We rec-
boprophylaxis. Early mobilisation and use of non-pharmaco- ommend multi-faceted interventions for VTE prophylaxis in
logical means of thromboprophylaxis should be exploited. In elderly and frail patients, including pneumatic compression
elderly patients, we suggest identification of co-morbidities devices, low molecular weight heparin (and/or direct oral
increasing the risk for VTE (e.g. congestive heart failure, anti-coagulants after knee or hip replacement) (Grade 1C).
pulmonary circulation disorder, renal failure, lymphoma, met-
astatic cancer, obesity, arthritis, post-menopausal oestrogen Published online 9 September 2017

This article is part of the European guidelines on peri- Introduction

operative venous thromboembolism prophylaxis. For Very few sets of guidelines have addressed the ageing
details concerning background, methods, and members
of the ESA VTE Guidelines Task Force, please, refer to: issue. No recommendations are directly dedicated to the
elderly, especially in the perioperative setting. However,
Samama CM, Afshari A, for the ESA VTE Guidelines if the venous thromboembolism (VTE) risk is known to
Task Force. European guidelines on perioperative increase with age, the bleeding risk is also increasing.
venous thromboembolism prophylaxis. Eur J Anaesthesiol
Therefore, it was of utmost importance to address the
2018; 35:73–76.
elderly issue in these guidelines.
A synopsis of all recommendations can be found in the
following accompanying article: Risk factors for venous thromboembolism in
Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE the elderly
Guidelines Task Force. European Guidelines on periop- Large population-based epidemiological studies globally
erative venous thromboembolism prophylaxis. Executive show that VTE is predominantly a disease of older age,
summary. Eur J Anaesthesiol 2018; 35:77–83. and it rarely occurs prior to late adolescence.1–8 Incidence
rates increase markedly with age for men and women, as

From the Sigmund Freud Private University and Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SK-L), Department of
Anaesthesiology, Aarhus University Hospital, Aarhus, Denmark (CF-E), Orthopaedic Surgery, University Hospital Saint Luc, Brussels, Belgium (ET), and Department of
Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania (GB)
Correspondence to Sibylle Kozek-Langenecker, Sigmund Freud Private University and Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Hans-
Sachs-Gasse 10-12, A-1180 Vienna, Austria
Tel: +43 1 40422 4040; e-mail: [email protected]

0265-0215 Copyright ß 2018 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000000705

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.

 European guidelines on perioperative venous thromboembolism 117

well as for deep vein thrombosis (DVT) and pulmonary Anderson and Spencer10 have identified and categorised
embolism.2,4,6 risk factors for VTE into
Cushman et al.2 conducted a longitudinal investigation (1) strong [odds ratio (OR) >10] – hip or leg fracture/
of VTE cause in a cohort of middle-aged (>45 years) replacement, major general surgery, major trauma,
and older patients in the United States (n ¼ 21 680), and spinal cord injury
followed them for 7.6 years. The age-standardised (2) moderate (2 < OR < 9) – arthroscopic knee surgery,
incidence of first-time VTE was 1.92 per 1000 per- central venous lines, chemotherapy, congestive heart
son-years. The incidence of first lifetime VTE or respiratory failure, HRT, malignancy, paralytic
increased with age, with rates among patients more stroke, previous VTE, thrombophilia
than 65 years old more than three times those in (3) weak (OR < 2) – bed rest for more than 3 days,
patients aged 45 to 54 years. The researchers reported increasing age, laparoscopic surgery, obesity,
that incidence was similar in men and women. How- varicose veins.
ever, above the age of 75 years, the rate in men was
twice that in women [5.5 (95% confidence interval (CI)
3.8 to 8.0) per 1000 person-years vs. 2.7 (95% CI 1.7 to In a prospective cohort study in four US communities
4.3) per 1000 person-years]. There was no antecedent involving 4859 participants aged 65 years and older, 52%
trauma, surgery, immobilisation or diagnosis of cancer of the sample were classified as having intermediate or
for 48% (175/366) of events. definite frailty.11 After adjustment for age, race, sex, BMI
and diabetes, the relative risk (RR) of total VTE for
Naess et al.4 conducted a case–controlled population- people who were frail compared with no frailty was 1.31
based study in a county of 91 194 residents aged more (95% CI 0.93 to 1.84). The comparably adjusted RR for
than 20 years in Norway. The incidence rate for all first idiopathic VTE was 1.79 (95% CI 1.02 to 3.13).
VTE events was 1.43 per 1000 person-years (95% CI 1.33
to 1.54); for DVT, it was 0.93 per 1000 person-years (95% Similarly, Leibson et al.12 found in a population-based
CI 0.85 to 1.02) and for pulmonary embolism it was 0.50 nested case–control study that, contrary to previous
per 1000 person-years (95% CI 0.44 to 0.56). The inci- assumptions, most VTE risk factors identified in non-
dence rates increased exponentially with age and were nursing home populations do not apply to the nursing
slightly higher in women than in men. home residents who may be characterised as frail. Nurs-
ing home residents with infection, substantial mobility
Silverstein et al.6 followed a population of a county in the limitations or recent general surgery should be consid-
United States (106 470 inhabitants) during a time period ered potential candidates for VTE prophylaxis.
of 25 years and found that the incidence of VTE rose
markedly with increasing age for both sexes, with pul- Tsai et al.13 have shown that among hospitalisations of
adults, age, sex, race and other variables were important
monary embolism accounting for most of the increase.
Significantly, the researchers found that the rate of determinants of VTE. Each of the following pre-existing
co-morbid conditions – AIDS, anaemia, arthritis, conges-
pulmonary embolism decreased markedly during the
study; it was approximately 45% lower during the last tive heart failure, coagulopathy, hypertension, lym-
phoma, metastatic cancer, other neurological disorders,
15 years of the study. This effect was seen for both men
and women, and it was seen for all age strata. The obesity, paralysis, pulmonary circulation disorders, renal
failure, solid tumour without metastasis and weight loss –
incidence of DVT, however, remained constant for
men across all age strata, decreased for women younger was associated independently with 1.04 (95% CI 1.02 to
1.06) to 2.91 (95% CI 2.81 to 3.00) times increased
than 55 years and increased for women older than
60 years. likelihood of VTE diagnosis. The presence of two or
more such conditions was associated with a 180 to 450%
More evidence for the relevance of age as a risk factor for increased likelihood of a VTE diagnosis.
VTE was published by Oger5 in a study of the incidence
Post-menopausal oestrogen replacement is associated
of VTE in a French community population. The
researchers found that the rate of VTE increased with with an increased risk of VTE, and this risk may be
highest in the first year of use.14 An estimated OR of 3.5
age. For patients older than 75 years, an incidence of
more than 1% was found. This study also reported that for VTE amongst users of HRT compared with controls
suggests that this medical population as an at-risk popu-
the rate of pulmonary embolism as a proportion of total
VTE increased with age. lation for VTE.1 Similarly, another study has revealed in
multi-variate analysis that the risk for VTE was even
A recent population-based study of residents of a large more increased among women who had lower extremity
New England metropolitan area has revealed that the fractures [relative hazard, 18.1 (CI 5.4 to 60.4)] or cancer
magnitude of VTE increases even more dramatically to [relative hazard, 3.9 (CI 1.6 to 9.4)] and for 90 days after
885/100 000 of the population in those who are 85 years inpatient surgery [relative hazard, 4.9 (CI 2.4 to 9.8)] or
and older.9 non-surgical hospitalisation [relative hazard, 5.7 (CI 3.0 to

Eur J Anaesthesiol 2018; 35:116–122

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
 118 Kozek-Langenecker et al.

10.8)].15 In addition, post-menopausal therapy with oes- (95% CI 1.1 to 22.0)] and immobility a high risk for
trogen and progestin increases risk for VTE in women developing postoperative VTE.
with coronary artery disease. These risks should be
In a population-based historical cohort study in the
considered when the risks and benefits of therapy are
United States, all (n ¼ 4833) residents undergoing a first
being weighed up.
arthroscopic knee operation during the 18-year period of
Diabetes remains a debatable risk factor for VTE in the 1988 to 2005 were followed for the incidence of deep
elderly as well as in the younger population. In a popula- venous thrombosis or pulmonary embolism. In total, 18
tion-based case–control study from the United States, developed postoperative VTE, all within the first 6 weeks
diabetes mellitus and diabetes complications were shown after surgery. Risks for postoperative VTE were signifi-
not to be independent risk factors of incident VTE.16 On cantly increased for advanced patient age [hazard ratio
the contrary, the most recent Taiwan longitudinal nation- 1.34 for each 10-year increase in patient age (P ¼ 0.03)]
wide cohort study indicated that type 2 diabetes mellitus and hospitalisation either before or after knee arthroscopy
patients carried greater risks of developing VTE than did (hazard ratio 14.1; P < 0.001).26
the general population.17 Further studies are needed to
Because pulmonary embolism risk rises faster than that of
develop sufficiently sound conclusions.
DVT, the relative incidence of pulmonary embolism and,
therefore, the fatal impact of VTE, also increases with
Risk factors for venous thromboembolism
age.27–29 It has been argued, however, that the associa-
and pulmonary embolism in the elderly
tion between age and VTE and pulmonary embolism
undergoing surgery
might be mediated by underlying co-morbidities that
Limited physiological reserves of older patients make
could be the actual risk factors.1,30
them more vulnerable to postoperative stress and ill-
ness.18 Frailty is broadly defined as a state of increased It has to be noted that age may be a proxy of immobility
vulnerability resulting from age-associated declines in and coagulation activation.31–33 Dagrosa et al.34 assessed
reserve and function across multiple physiological sys- 12123 patients who underwent robotic-assisted laparo-
tems, such that the ability to cope with everyday or acute scopic radical prostatectomy (RALRP) in the timeframe
stressors is compromised.19 Lee et al.20 found that age at 2009 to 2012. Univariate analysis demonstrated that nine
least 70 years (OR 5.61), at least two co-morbidities (OR co-morbidities were associated with age: history of
13.42) and white blood cell count of more than congestive heart failure, myocardial infarction (MI), cere-
10 000 ml1 (OR 17.43) were independent risk factors brovascular attack (CVA), transient ischaemic attack,
for postoperative VTE in a cohort of Korean patients bleeding disorder, chronic obstructive pulmonary dis-
undergoing major abdominal surgery for colorectal ease, percutaneous coronary intervention, cardiac surgery
cancer. and American Society of Anesthesiologists’ physical
status (P < 0.05). Postoperatively, five medical complica-
Zhang et al. undertook a systematic review to assess the
tions were associated with age-related co-morbidities:
risk factors for VTE after total hip arthroplasty (THA)
MI, CVA, pneumonia (PNA), DVT, pulmonary embo-
and total knee arthroplasty (TKA). They included level I
lism and urinary tract infection (UTI). On multi-variate
and level II studies published between 2003 and 2013 on
analysis, age was found to be an independent risk factor
risk factors for VTE of total joint arthroplasty.21,22 In
for postoperative PNA (P < 0.05), but not for MI
total, 45 articles were included in their review. Risk
(P ¼ 0.09), UTI (P ¼ 0.3), CVA (P ¼ 0.2) or DVT/pulmo-
factors found to be associated with VTE after both
nary embolism (P ¼ 0.7). The researchers concluded that
THA and TKA included older age, female sex, higher
although patient age may generate concern for medical
BMI, bilateral surgery and surgery time more than 2 h.
complications following surgery, the results suggested
The researchers did not provide a (pooled) risk estimate.
that age is not an independent risk factor for these
Sun et al.23 retrospectively assessed a cohort of 537
medical complications after RALRP.
Chinese patients who underwent knee arthroscopy and
found age a strongly significant risk factor for DVT.
Are risk factors still important if the elderly
Saleh et al.24 conducted a systematic review to assess the
are going through a perioperative early
incidence of VTE after shoulder arthroplasty. They
mobilisation programme?
included 14 studies and reported a cumulative incidence
Pearse et al.35 carried out a level III study on the result of
of 0.2 to 16%. The most prominent risk factors for
achieving early walking following total knee replacement
development of VTE were previous VTE, thrombophi-
after implementation of a rapid rehabilitation protocol.
lia, major surgery, advanced age (>60 years), current
They assessed the influence of the protocol on the
malignant disease, immobility and bed confinement.
development of DVT as determined by Doppler ultra-
Akpinar et al.25 retrospectively assessed a cohort of 1206 sound scanning on the fifth postoperative day. Early
patients who had undergone THA, TKA or trauma mobilisation was defined as beginning to walk less than
surgery and found advanced age (65 years) [OR 4.9 24 h after knee replacement. Sample size was 97 patients

Eur J Anaesthesiol 2018; 35:116–122

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 European guidelines on perioperative venous thromboembolism 119

who received 122 knee replacements. A historical cohort probability of VTE increased, alongside poorer/reduced
was used for comparison (98 patients, 125 TKAs). All the pulmonary function that increased risk of PNA, longer
patients received low molecular weight heparin LOS, further deconditioning and a greater need for
(LMWH) thromboprophylaxis and wore compression postoperative rehabilitation. To counteract these risks,
stockings postoperatively. In the early mobilisation the researchers introduced a protocol including early
group, 90 patients (92.8%) began walking successfully extubation and early mobilisation. This protocol included
within 24 h of their operation. The incidence of DVT a range of motion exercises on the day of surgery, dan-
decreased from 27.6% in the control group to 1.0% in the gling at the bedside and being out of bed to a chair. The
early mobilisation group (P < 0.001). postoperative protocol included being out of bed to a
chair two to three times per day, and walking in the room/
Husted et al.36 conducted a level IV study and assessed
hall. Both protocols of early extubation/mobilisation suc-
1977 consecutive, un-selected patients who were oper-
cessfully reduced the number of complications and LOS
ated on for primary THA, TKA or bilateral simultaneous
for this patient population.
TKA (BSTKA) in a fast-track setting between 2004 and
2008. All patients received DVT prophylaxis with
LMWH starting 6 to 8 h after surgery until discharge. When do we start venous thromboembolism
An overall risk of death potentially related to the opera- prophylaxis and at what dose in the elderly?
tion of 0.15% was found, which was deemed to compare Recommendations for VTE prophylaxis in elderly
favourably with the literature. During the last 2 years (854 patients are typically extrapolated from non-age-specific
patients), when patients were mobilised within 4 h post- VTE prophylaxis trials. There are relatively few high-
operatively, and the duration of DVT prophylaxis was quality studies to guide decisions concerning the timing
shortest (1 to 4 days), the mortality was 0% (95% CI 0 to of VTE prophylaxis in the elderly population.
0.5). The incidence of DVT in TKA was 0.60% (0.2 to
Ramanathan et al.40 investigated the impact of delayed
2.2), in THA it was 0.51% (0.1 to 1.8) and in BSTKA it
initiation/interruption of chemical prophylaxis on VTE
was 0% (0 to 2.9). The incidence of pulmonary embolism
rates in 9961 surgical patients. Interrupted prophylaxis
in TKA was 0.30% (0.1 to 1.7), in THA it was 0% (0 to 1.0)
(interruption for >24 h) was associated with more VTE
and in BSTKA it was 0% (0 to 2.9).
compared with complete prophylaxis (started within 24 h
In 2013, a group of researchers published results from a of admission, no interruptions) (10.2 vs. 2.0 per 1000,
study including 4659 arthroplasty procedures.37 They P < 0.01) and 5.2 greater odds. Admission to a surgical
found 90-day postoperative rates of symptomatic pulmo- service and prolonged hospital stay were independently
nary embolism events and VTE of 0.84 and 0.41%, associated with increased likelihood of VTE.
respectively, in patients with length of stay (LOS) 5 days
Nunez et al.41 observed in a single-institution prospective
or less and in-hospital thromboprophylaxis only. They
non-randomised study that weight-adjusted dosing of
compared their rates with literature: two Danish nation-
enoxaparin had resulted in an increase of goal anti-Xa
wide studies found symptomatic VTE in more than 1% of
levels from 19 to 59% (P < 0.0001).
THA and TKA procedures despite prolonged prophy-
laxis, and the incidence was increasing across the study There are limited high-quality data comparing different
period (1995 to 2007). The researchers attributed the LMWH with each other or with UFH in elderly patients.
difference between their data and the literature to the In a single-centre retrospective study, 210 patients
fast-track set-up including early mobilisation in their (median age 81 years) were treated with fondaparinux
study, and as LOS in Denmark was about 11 days in 1.5 or 2.5 mg daily. The authors concluded that, in elderly
year 2000. acutely ill-hospitalised medical patients, thromboprophy-
laxis with fondaparinux 2.5 or 1.5 mg daily was well
Chandrasekaran et al.38 published a rather small level III
tolerated and effective in preventing VTE without sig-
study in which 50 patients who underwent mobilisation
nificantly increasing bleeding risk.42
on the first postoperative day were compared with 50
patients who had strict bed rest on the first postoperative Another group has observed that preoperative subcuta-
day. There was a significant reduction in the incidence of neous heparin has significantly reduced postoperative
VTE complications in the mobilisation group (seven in VTE events (17.6 vs. 2.6%, P ¼ 0.035) when compared
total) compared with the control group (16 in total) with intermittent compression boots and postoperative
(P ¼ 0.03). Furthermore, in the mobilisation group, the pharmacoprophylaxis.43
odds of developing a thromboembolic complication was
The DIRECT (Dalteparin’s Influence on the Renally
significantly reduced the greater the distance the patient
Compromised: Anti-Ten-A) trial included critically ill
mobilised (P ¼ 0.005).
patients (n ¼ 138) with a creatinine clearance less than
Pertaining to the field of cardiac surgery, Freeman and 30 ml min1 given dalteparin (5000 IU daily) in the pro-
Maley39 previously observed that, if ICU patients on phylactic setting. No bioaccumulation of dalteparin was
mechanical circulatory support were kept in bed, their observed.44 Another randomised clinical trial that

Eur J Anaesthesiol 2018; 35:116–122

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 120 Kozek-Langenecker et al.

enrolled patients with a median creatinine clearance of lipid-lowering drugs, statins are therapeutic and also
34.7  11.4 ml min1 randomised to receive enoxaparin preventive against VTE among at-risk medical inpati-
(40 mg) or tinzaparin once daily in the prophylactic ents and also the general population in a dose-depen-
setting found that factor Xa did not accumulate signifi- dent manner, although this effect has not been observed
cantly in patients who were given tinzaparin but did in the elderly population, as was shown in the PROS-
accumulate in the enoxaparin group (P < 0.0001).45 PER study.54 Further, interpreting the JUPITER trial
Tinzaparin might, therefore, be preferable in patients results, Perez and Bartholomew55 caution against sub-
with renal insufficiency. stitution of proven prophylaxis and anti-coagulation
with statins, especially for patients at high risk of
A recent Canadian consensus stated there is no high-level
VTE. The most recent meta-analysis by Sardar
evidence to recommend one LMWH or UFH over
et al.56 concluded that, in participants of clinical trials
another in elderly patients with active malignancy46. In
aged 75 and older, DOACs did not cause excess bleed-
contrast, Tincani et al.47 recommend UFH to be the anti-
ing and were associated with equal or greater efficacy
coagulant of choice in the treatment of patients with renal
than conventional therapy.
failure, at high risk of bleeding, and in whom rapid
reversal of anti-coagulation may be required.
Recommendations
Limongelli et al.48 have conducted analysis on 1018  Age over 70 years is a risk factor for postoperative VTE
consecutive patients who had undergone total thyroidec- (Grade B).
tomy for benign and malignant diseases with/without  In elderly patients, we suggest identification of co-
preoperative prophylaxis and found the risk of develop- morbidities increasing the risk for VTE (e.g. con-
ing VTE was eight times less than developing a gestive heart failure, pulmonary circulation disorder,
postoperative bleed. renal failure, lymphoma, metastatic cancer, obesity,
arthritis, post-menopausal oestrogen therapy) and
The most recent Cochrane Database Systematic Review, correction if present (e.g. anaemia, coagulopathy)
although not specifically addressing the elderly, con- (Grade 2C).
cludes that multi-faceted interventions (graduated com-  We suggest against bilateral knee replacement in
pression stockings, sequential compression devices and elderly and frail patients (Grade 2C).
anti-coagulant medications such as LMWH) are well  We suggest timing and dosing of pharmacological VTE
tolerated and can prevent blood clotting in patients at prophylaxis as in the non-aged population (Grade 2C).
risk of these complications.11  In elderly patients with renal failure, low-dose un-
A recent meta-analysis included nine phase 3 randomised fractionated heparin may be used or weight-adjusted
controlled trials comparing direct oral anticoagulants dosing of LMWH (Grade 2C).
(DOACs) against LMWH in the prevention of VTE in  In the elderly, we recommend careful prescription of
29 403 elective post-arthroplasty patients.49 The elderly postoperative VTE prophylaxis and early postopera-
population was defined as adults aged at least 75 years. tive mobilisation (Grade 1C).
The risk of VTE or VTE-related deaths in elderly  We recommend multi-faceted interventions for VTE
patients after elective arthroplasty was similar with prophylaxis in elderly and frail patients, including
DOACs compared with LMWH (OR 0.62, 95% CI pneumatic compression devices, LMWH (and/or
0.30 to 1.26; P ¼ 0.18; I ¼ 44%) but bleeding risk was direct oral anti-coagulants after knee or hip replace-
significantly lower (OR 0.71, 95% CI 0.53 to 0.94; ment) (Grade 1C).
P ¼ 0.02; I ¼ 0%). Analysis of individual DOACs showed
superior efficacy but similar safety for apixaban when Acknowledgements relating to this article
compared with LMWH. Efficacy and safety profiles Assistance with the guideline chapter: none.
of rivaroxaban and dabigatran were similar to LMWH.
Financial support and sponsorship: expenses for two meetings of
In elderly patients, after elective arthroplasty, the VTE Task Force (Brussels and Berlin) were covered by the
DOACs have demonstrated similar efficacy but superior ESA for the ESA members.
safety when compared with enoxaparin for VTE pro-
phylaxis. Conflicts of interest: none.

Statins are currently under investigation as anti-throm-

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