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ORIGINAL ARTICLE

All I want for coagulation


K P Nunn*, M R Bridgett*, M R Walters* and I Walker*
*Faculty of Medicine, University of Glasgow, Glasgow, Scotland, UK; Glasgow Royal Infirmary, Glasgow, Scotland, UK;

Western Infirmary and Gartnavel General Hospital, Glasgow, Scotland, UK


E-mail: m.bridgett@hotmail.co.uk

Abstract
Evidence-based medicine underpins modern practice of medicine. This paper describes a fictional consultation between Santa Claus and a doctor regarding deep vein thrombosis (DVT) prophylaxis, giving a
review of the evidence for DVT prophylaxis in travellers while exposing the difficulty in applying evidence
to atypical clinical encounters. Medline and the Cochrane Library were searched, and guidelines
reviewed. Keywords used were DVT, thromboembolism, deep vein thrombosis and air travel-related
venous thromboembolism. All relevant studies found, have been included in this review, with additional
studies identified from the references in these articles. In conclusion, compression stockings, with or
without a one-off dose of either aspirin or heparin, are the most evidence-based approaches for prophylaxis in someone with established risk factors for DVT prior to a long-haul flight. Simple exercises
should also be encouraged.
Keywords: DVT, thromboembolism, deep vein thrombosis, air travel-related venous thromboembolism,
Santa

Introduction
Approaching Christmas, travel health consultations will
involve patients with a range of intentions: city-breaks,
snow-sports and Christmas sunshine. Most will be low
risk and have an evidence-base for advice.
Yet what if Santa presented for advice on deep vein
thrombosis (DVT) risk during his long-haul flight? A
link between air travel and venous thromboembolism
(ATVT) is accepted1, with a symptomatic frequency of
1%2 and a symptomless frequency of 10%.3 DVT can be
complicated by venous thromboembolism (VTE) to the
lung, pulmonary embolus (PE), and in the context of airtravel is referred to by some authorities as ATVT; for simplicity this paper will refer to DVT, as this is the accepted
aetiology.
Santa is a statistical outlier. Even adjusting for his
demographics and establishing his baseline coagulation
risk may not enable us to use aviation data accurately, as
a flying sleigh is a different physiological environment to
a pressurized cabin. Regardless, there remains relatively
little data on coagulation in extreme environments.

Scenario
Dr Van Testatus, during his travel clinic, had just convinced a patient that typhoid was unlikely in Chamonix
during December, when an elderly jolly gentleman
entered and introduced himself as Santa. He reported
that he was self-employed and therefore did not have
access to an occupational health department but was due
DOI: 10.1258/smj.2011.011154

to fly a sleigh around the world in 15 days time and felt


concerned about DVT risk (he had no psychiatric
history). Dr VT considered how he would handle this
case, and fitting of his Latin name, decided to work
through the problem methodically.
Van Testatus considered risk factors, including his
origin and family/travel history to establish Santas risk.
The risk of DVT and its complications due to flight have
received relatively recent attention.4 Van Testatus needs
to know flight-related risks that will have different characteristics to conventional flight. He divides the risk into
individual and travel-related factors (Table 1).

Individual risk factors


Determining Santas demographic risk is difficult, as his
origin is unknown. Saint Nicholas was a Greek Bishop
in fourth century Byzantium, suggesting eastern
European/western Asian origin. He may be of Nordic
origin, based on a sixth century Pagan God who, during
the Germanic holiday of Yule, led flying hunting parties.
Santas existence in Britain emerged in the 17th century,
implicating Alpine or Mediterranean origin. Todays
Santa appeared in the 1930s, making him a North
American octogenarian.7 This helps to assess the suitability of studies, e.g. if study design excluded someone
of 1700 years, then it will be less relevant for consideration
in this case.8,9 Additionally the incidence of DVT varies
geographically.
Following a DVT, the risk of another is 3 10% per
year with approximately 50% occurring in the
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Nunn et al.

Table 1 Factors that may increase the risk of DVT in airline travellers
above the baseline population (adapted from Clarke et al. 5)
Individual risk factors

Travel risk factors

Hereditary or acquired
prothrombotic clotting
disorders
Previous DVT/VTE

Prolonged immobilization, e.g.


narrow economy class seats
(window seat)
Reduced fluid intake (may be
related to dehydration and low
humidity)
Hypobaric hypoxia6

Older age
Pregnancy and the postpartum
state (not relevant to Santa)
Recent surgery or trauma
Malignancy
Smoking status
Chronic heart disease (other
chronic disease, especially
cardiovascular diseases)
Obesity
Medication (oral contraceptive,
hormone replacement)

DVT, deep vein thrombosis; VTE, venous thromboembolism

contralateral limb, suggesting predisposing physiology


rather than local damage. If Santas had a DVT then his
risk is increased.10
Obesity is a risk factor for DVT.11 18 Is Santa obese?
There are no definite values for Santas height or weight.
Most images of Santa portray him as being of average
height. Canada, Denmark, Norway and Sweden have
claimed Santas citizenship. If we average the average
heights of these nations we get 1.79 m.19 Weight is trickier; to be obese at a height of 1.79 m Santa would have
to weigh 96.4 kg. For Santa to visit every household,
he would have to travel at speeds approaching the speed
of light. At such speeds Santas mass, and therefore body
mass index (BMI), would tend towards infinity. So
Santas BMI will be 30 during travel. Some studies
suggest that obesity is a weak risk factor for DVT20,21
and risk of DVT based on obesity as a sole risk factor
is low.22
Van Testatus must speak to and examine Santa to fully
establish individual risk.

Travel risk factors


Commercial cabins are pressurized. A prolonged period in
a cabin is considered a risk factor for DVT.1,8,9,23,24 The
World Health Organization (WHO) WRIGHT project
has ongoing investigations into travel health and
preventation.25
Santas open sleigh poses problems, maintaining a
festive look is difficult, but does the lack of a pressurized
cabin affect coagulability?
Cabin pressure should be equivalent to 2438 m
(750 hPa) above sea level, equivalent to breathing 15%
O2 at sea level (1016 hPa).26 In a study of 45 Boeing
747-400 flights with an average flight time of 10.5 hours,
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cabin pressure was never below 750 hPa and only


dropped below 800 hPa for 2% of the flying time.26 This
can cause a desaturation to 90 93% due to a secondary,
relative hypoxia (hypobaric hypoxia) which may reduce
fibrinolysis;6,27 however, evidence from climbers suggests
that hypoxia causes changes resembling disseminated
intravascular coagulation, often seen in altitude
illness.28,29 Recreating flight atmosphere in a hypobaric
oxygen chamber demonstrates increased plasma thrombotic activity.3,30 Santas environment is more extreme.
Bendz et al.31 agree that being sedentary is a risk factor
for DVT, but suggest that hypobaric hypoxic activation
of coagulation is also important. However, this was criticized for methods and outlying findings which were unjustified. Thrombosis risk increases above 3000 m.28 Cooler
temperatures (vasoconstriction) will raise viscosity.
Open-sleigh flying will increase insensible loss, exacerbated by alcohol, although there is evidence that dehydration does not affect coagulation during flight.32 Since
he resides at the North Pole, he will be a sea-level
visitor to altitude potentially developing physiological
risk factors.29 The significance of altitude on coagulation
physiology remains unresolved and there is no evidence
applicable to Santa.
Is the journey itself a risk? One large study demonstrated that for a mean journey time of 10.5 hours, travel
did not significantly increase DVT incidence, whereas
incidence of DVT was higher for any form of travel
greater than three hours with an additional risk factor,
including for aircraft travel over eight hours with
additional risk factors. The authors concluded that
additional risk factors play a role in the incidence of travelrelated DVT.23 Supporting studies found thrombosis risk
factors present in 82%33 of cases of DVT (PE) and 18%
of controls.10 There is a two-fold higher risk of DVT if
seated by the window.32 Santas sleigh has a bench rendering the last point irrelevant, but at this time Van Testatus
was speculating.

Using the Testatus


There is no research to directly answer our question, so
Van Testatus must evaluate the existing evidence.
It is difficult to predict DVT in hospital or the community.21 Screening is expensive, insensitive and not costeffective compared with prophylaxis.34
The incidence of DVT is essentially 0.001%.12,35 40
Van Testatus could re-assure Santa but would be sensible
to advise him, i.e. someone with risk factors, to take precautions. Van Testatus could cover the contents of
Table 2.
Guidance on DVT is under development by the
National Institute of Clinical Excellence (NICE);
Scottish Intercollegiate Guidance Network (SIGN)
includes a section on DVT. The American College of
Chest Physicians (ACCP) agrees with SIGN for certain
situations, not including long distance travel. The ACCP
does not recommend the use of aspirin.41

All I want for coagulation

185

Table 2 Outline of possible prophylaxis against DVT: SIGN, NICE


and ACCP
Source

Risk factor

SIGN 62 (grade D evidence, role


greatly disputed)
SIGN 62 (grade D evidence, role
greatly disputed)
SIGN 62 (NICE guidance due
November 2009)
SIGN 62 ACCP, (NICE guidance
due November 2009)
SIGN 62, ACCP, (NICE guidance
due November 2009)
SIGN 62, ACCP, (NICE guidance
due November 2009)

Ensure good hydration


Restrict alcohol and coffee intake
Leg exercises
Graduated elastic compression

stockings (GECS)
Single dose of aspirin 150 mg
Single injection of low molecular

weight heparin

New NICE guidance may or may not include these areas


The ACCP does not make recommendations for travel prophylaxis
specifically

Immobility as a risk factor was suggested following


studies of bed rest42,43 and increases the risk of DVT
10-fold.11,44,45 There is agreement to encourage exercises
to reduce venous stasis.35,46 48
Van Testatus suggests pressing the balls of the feet
against the floor and walking, but Santa may find this difficult while on the sleigh. It may be feasible to land on one
roof per village and hop from roof to roof, though the
orthopaedic doctor (bound for Chamonix) may disagree.
Van Testatus discusses graduated elastic compression
stockings (GECS). GECS increase blood flow, decreasing
venous stasis and the risk of DVT. They would not interact
with medications, are especially useful in patients where
there is an unacceptable risk of bleeding versus the benefits
of pharmacological prophylaxis and can be supplied in
quantity for the trip ( previously Santa thought stockings
simply made a good stocking-filler). Contraindications
are shown in Table 3.12
Above knee stockings are advised because most trials
used them34,41,47,49,50 and the trials that included below
knee were small.51,52 The evidence that they work in
patients has been questioned by the Clots in Legs Or
sTockings after Stroke (CLOTS) study, which suggests
no benefit from thigh length stockings. These data come
from trial 1, which looked at reducing the risk of above
knee DVT following acute stroke. Trial 2 will compare
Table 3 Contraindications and cautions for the use of graduated
elastic compression stockings (adapted from SIGN 6212)
Contraindications

Cautions

Massive leg oedema


Pulmonary oedema
(e.g. heart failure)
Severe peripheral arterial disease
Severe peripheral neuropathy
Major leg deformity

Select correct size


Apply carefully, applying toe
hole under toe
Check fitting daily
Do not fold down
Remove daily for no more
than 30 minutes

Dermatitis

full-length stockings with below knee ones.53 A


meta-analysis showed that asymptomatic DVT occurred
in 8.6% of patients wearing GECS, compared with 27%
of controls.49 These results are supported by a previous
meta-analysis54 and studies from the 1950s.50,55 GECS
used for patients differ from those used by passengers,56
and the evidence for use in passengers is weaker. The randomized controlled trials (RCTs) involving aviation
showed a reduction in the incidence of asymptomatic
DVT.3,57 However Scurrs study was criticized;10,30 patients
with DVT did not have a raised D-dimer and an incidence
of 10% is not observed on a daily basis. For Testatus to
know how comparable the studies are for Santa, he needs
to know how long Santa will be airborne for. Does he fly
on Christmas Eve only, or make earlier trips to deposit
gifts in regional storage facilities?
Pharmacological options are aspirin, heparin and warfarin. Aspirin is not universally recommended because of
bleeding risk. There is stronger evidence that heparin is
effective for the prevention of DVT. Warfarin would be
unsuitable because of potential loss to follow-up and an
erratic diet at the foot of the chimney. Newer agents,
Dabigatran and Rivaroxaban, have been approved for
UK use specifically for orthopaedic patients. Although
not suitable as prophylaxis for Santa, they may prove
useful if he slips off an icy roof.
Fifty-three antiplatelet (mostly aspirin) RCTs were
included in a meta-analysis, which showed a significant
decrease in risk of DVT in surgical patients.44,58 A larger
study, the Pulmonary Embolism Prevention (PEP) trial,
confirmed these findings.59 The PEP trial used 160 mg/
day59 and SIGN recommend a one-off dose of 150 mg
(based on available formulations) for people with risk
factors undertaking a long-haul flight,12 but the risks
versus benefits are unknown due to lack of research. The
ACCP do not recommend aspirin due to the increased
risk of bleeding.41

Final considerations
The evidence suggests that it is vital to establish previous
DVT as a risk factor. Unfortunately for Santa, studies
suggest that continuous flight and multiple flights are
equal risk factors.25 Distance may be important as there
is risk in long distance flights with stopovers.8 However,
unless Santa flies to Charles de Gaulle, he would not
have been included in this data.
Why are there limited data? The usabilty of data
depends upon study design, cohort, validity and the population to which one wishes to apply the findings. Complex
studies often raise questions in ethical review and this
delays research.60 The NZATT study excluded patients
with a positive D-dimer, which mainly excluded elderly
patients.2 People with risk factors are often excluded.61
The greatest, common, problem facing us is a lack of
evidence. Research has been done on flight DVT, but
approaches are inconsistent, making it impossible to
collate data. We need a consensus on the definition of
long-haul flights because ,2 hours,8 .3 hours,23 .4
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Nunn et al.

hours1 and .8 hours9,23,24 are used. Endpoints differ; early


VTE,8 VTE,33 oedema or superficial or deep VT,24 asymptomatic3,9,23 or symptomatic DVT.23
We may never get an answer regarding the relationship between flight and increased risk of DVT because
the baseline general population risk is so low as to
require a cohort of over 40,000 to accurately assess
increased risk.5

Recommendations
Van Testatus could recommend stockings following the
Cochrane review. However, in the trials used for this
analysis there were no symptomatic DVTs, PEs or deaths,
and so the effect of stockings on these endpoints was undetermined.5 However, these data may not apply to the
seated position.
Therefore Van Testatus could advise compression
hosiery and encourage movement on the flight. He could
consider a one-off dose of 150 mg aspirin, if he was satisfied
with establishing gastrointestinal-bleed risk and providing
adequate gastric protection, or a single-dose of prophylactic low molecular weight heparin prior to departure. Dr VT
will need to update his opinion as further WRIGHT and
CLOTS data become available.
Provenance statement: KN and MB are both Academic
Foundation Programme (a recent initiative in the UK to
promote development of future academic clinicians) clinical doctors. KN suggested this clinical problem, and MB
thought this was essential, so KN and MB prepared the
manuscript. They then sought mentorship from MW and
expert opinion from IW, who critiqued the structure,
format and evidence base. Professor Michael Greaves
(Faculty of Medicine, University of Aberdeen) provided
editorship and local peer review, critically contributing
to the text. The final decision to submit was made by
KN and MB, and both act as guarantors. KN and MB contributed equally to the text.
Conflict of interest: Both KN and MB report having
received gifts from Santa but do not feel able to accurately
declare the net value, they advocate Santas work but
receive no direct reward, nor travel reimbursement for
doing so. There is no known financial or other relationship
between the hospitals, University and Santa. KN and MB
also report having left mince pies, carrots and a wee tipple
out for Santa and his reindeer in the past. They do not
believe that their interest in Santa has any direct bearing
on their clinical or academic practice. MW, IW and MG
deny any interest in Santa that would jeopardize their professional autonomy.

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