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Thomas Charles ()
Medical Research Institute of New Zealand, Private Bag
7902, Wellington 6242, New Zealand. Email:
Thom.Charles@mrinz.ac.nz
Thomas Charles · Bridget Healy · Kyle Perrin
Richard Beasley
Medical Research Institute of New Zealand, Wellington,
New Zealand
Deborah Mackintosh
Pacific Radiology Limited, Wellington, New Zealand
Bridget Healy · Kyle Perrin · Mark Weatherall
Richard Beasley
Capital & Coast District Health Board, Wellington,
New Zealand
Mark Weatherall
University of Otago Wellington, Wellington,
New Zealand
Adv Ther (2011) 28(3)
DOI 10.1007/s12325-010-0107-5
ORIGINAL RESEARCH
Merino Wool Graduated Compression Stocking
Increases Lower Limb Venous Blood Flow: a Randomized
Controlled Trial
Thomas Charles · Deborah Mackintosh · Bridget Healy · Kyle Perrin · Mark Weatherall · Richard Beasley
Received: November 17, 2010 / Published online: February 14, 2011
© Springer Healthcare 2011
ABSTRACT
Introduction: Graduated compression stockings
represent a nonpharmacological approach to
reduce the risk of deep vein thrombosis (DVT)
and pulmonary embolism (PE) due to prolonged
immobility through reducing lower limb venous
stasis. A novel merino wool, double-layer, below-
knee graduated compression stocking has
been developed to reduce the risk of air travel-
related DVT and PE. Methods: Twenty healthy
adult participants were randomized to wear
the novel graduated compression stocking on
either the left or right leg. Doppler ultrasound
measurements of popliteal venous blood flow
were made on both legs over a 120-minute
period. The primary outcome was peak systolic
velocity in the popliteal vein at 120 minutes.
Secondary outcomes included mean flow
velocity, total volume flow, vein cross-sectional
area, and change in ankle and calf measurements.
Results: The popliteal vein peak systolic velocity
was 0.35 cm/s (95% confidence intervals [CI],
0.22 to 0.49, P<0.001) higher with stocking
use at 120 minutes, a difference of 24%. Mean
flow velocity and total volume flow were also
significantly higher with stocking use. Ankle and
calf circumference were decreased with stocking
use, with an overall difference of –6.3 mm
(95% CI, –11.3 to –1.2, P=0.021) and –7.9 mm
(95% CI, –13.3 to –2.4, P=0.011), respectively.
Conclusion: The novel merino wool double-
layer, below-knee graduated compression
stocking increases lower limb venous blood
flow during prolonged seated immobility. Its
use is likely to reduce the risk of DVT and PE
in situations of prolonged seated immobility,
such as long-distance air travel. The reduction
in lower limb swelling associated with their
use suggests that the stockings are likely to
2 Adv Ther (2011) 28(3)
have utility in the treatment of chronic venous
insufficiency and lymphedema.
Keywords: blood flow; compression stockings;
Doppler ultrasound; popliteal vein; venous
thromboembolism
INTRODUCTION
Prolonged seated immobility is a common and
important risk factor for the development of
venous thromboembolism (VTE), including
deep vein thrombosis (DVT) and pulmonary
embolism (PE).1-4 The risk of VTE with prolonged
seated immobility may occur in a number of
different situations including long-distance air,
car, or train travel, work, and recreation.1-16 The
most important mechanism contributing to the
risk of DVT is reduced blood flow in the deep
veins in the lower limbs.
Graduated compression stockings represent a
nonpharmacological approach in reducing the
risk of DVT with associated prolonged immobility
through reducing venous stasis and enhancing
venous blood flow.17-20 The effectiveness and
simplicity of their use have made them popular
in preventive care, both in the hospital setting
and amongst travelers. In considering new
designs of graduated compression products, it
is important to determine their physiological
effects on venous hemodynamics. In this study,
we have investigated the effect on lower limb
venous blood flow with a novel merino wool
below-knee graduated compression stocking.
METHODS
Participants
Twenty adult (13 female) participants aged
between the ages of 18 and 65 years old were
recruited into the study from a volunteer database.
Exclusion criteria included a history of previous
or current DVT, pregnancy (which may alter
lower limb venous return from compression at
the level of the iliac vein), history of previous
or current peripheral vascular disease, or any
other lower limb abnormality considered by the
study researcher to be inappropriate for wearing
a graduated compression stocking.
Eligible participants gave written informed
consent, and underwent anthropometric
measurements including weight, height, and
body mass index, as well as several lower leg
measurements which were used to ensure that
a correctly sized compression stocking was
supplied. Participants were randomized to wear
a graduated compression stocking on either their
left leg or right leg, by a computer-generated
random allocation supplied by a biostatistician.
Participants subsequently attended the
ultrasound facility for measurements of popliteal
venous blood flow and other outcomes.
Participants were requested to refrain from
undertaking any strenuous physical exercise,
such as running, rowing, or cycling, for 24 hours
before the ultrasound examination. Light-to-
moderate physical activity, such as walking or
swimming, was considered acceptable prior to
the appointment. Before testing, participants
were rested quietly for 10 minutes. Participants
then sat upright on padded chairs, with their
feet placed flat on the floor in front of them.
The personally sized compression stocking
was applied according to the randomization
schedule, and the other leg served as the control.
An angle of 120 degrees between the femur
and the tibia of both legs was achieved using a
goniometer, to standardize the degree of flexion
between patients. This position also permitted
the sonographer enough room in the popliteal
fossa to position the ultrasound probe. The feet
were elevated until the thigh was horizontal to
the floor, in an attempt to limit any venous flow
Adv Ther (2011) 28(3) 3
impairment caused by compression exerted by
the edge of the seat on the back of the thigh. The
participants were instructed not to move their
feet and to try to keep their leg muscles relaxed
until the conclusion of the study measurements.
An experienced sonographer used a Toshiba
Aplio XG ultrasound machine with a linear 8
probe (Toshiba America Medical Systems Inc.,
Tustin, California, USA) to measure popliteal
vein blood flow parameters at 0, 30, 60, and
120 minutes after the stocking was applied.
The mean of two measurements was used
to determine flow at each time point. The
Doppler angle of insonance was standardized at
60 degrees to the popliteal vein at the level
of the crease in the popliteal fossa. A small
Doppler sampling gate of 2.5 mm was used to
minimize any interference by arterial pulsations
on the tracings. During the measurement
process the subjects were asked not to move
at all, not to talk, and were encouraged to
maintain relaxed, even respiration, to reduce
interference with hemodynamics that can be
seen with deeper breathing. Due to the length
of the stocking and the location of the vein
segment scanned, it was not possible to blind
the ultrasonographer to which leg had the
stocking applied.
The primary outcome variable was the
peak systolic velocity in the popliteal vein.
Preplanned secondary outcome variables were
mean flow velocity, total volume flow, and vein
cross-sectional area. After the study started, it
was noted that the nonstocking leg of several
of the participants was swollen, in comparison
with the leg to which the stocking was applied.
To further assess this informal observation, the
leg circumference was measured at a level just
above the lateral and medial malleolus, and at
the widest part of the calf, prior to application
and after the stocking was removed in the final
eight subjects studied.
Figure 1. Encircle Class 1 below-knee graduated two-layer
therapy structure and application.
Figure 2. Encircle “bridge” closure and pressure
release mechanism. Back view of the outer layer of the
compression garment.
Inner Layer
10-15 mmHg
Inner Application
Back View with Zipper Open (Down)
Legend.
Bridge Panel sewn in under zip
Zipper
Zip slider and handle
Back View with Zipper Closed (Up)
Outer Application Outer Zipper
Down
Outer Zipper Up
Encircle Class 1 Two Layer Therapy Structure
Encircle Class 1 Two Layer Application
Encircle Outer Layer Bridge Closure & Pressure Release Mechanism
Outer Layer Encircle Class 1 Therapy
16-21 mmHg
4 Adv Ther (2011) 28(3)
“Encircle” Graduated Compression Stocking
The study intervention was the “Encircle”
product - a novel, two-layered, Class 1, below-
knee graduated compression stocking, with a
composition of up to 45% merino wool, 40%
elastane, and 15% polymide, manufactured by
The Merino Company (Levin, New Zealand). The
Encircle compression system is comprised of an
inner layer together with an outer layer, which
incorporates a novel zipper with an elasticized
“bridge” closure mechanism (Figures 1 and 2).
This mechanism facilitates the application of the
outer layer over the inner layer, and protects the
user from potential pressure caused by the zip.
The inner layer exerts 10-15 mmHg of pressure;
upon zipping the outer layer of the garment
closed over the inner layer, a total compression
of 16-21 mmHg (Class 1) is achieved.
In contrast to the synthetic fabrics used in the
majority of compression hosiery available, merino
wool is a natural protein fiber with hygroscopic
properties, which helps to provide a healthy
skin environment underneath the stocking.21-23
Merino wool fibers have a smaller diameter than
most other types of wool, so help to minimize
skin irritation. Stockings were worn straight out
of the packet without any prewashing.
Statistical Methods
Paired t-tests compared the outcome variables
(the mean of two readings) for the stocking
use, compared to no use, at each time point
separately, and also for the change from baseline.
The primary outcome was popliteal peak systolic
velocity at 120 minutes. A mixed linear model
was used to estimate the overall difference
between wearing stockings or not, the effect
of time, and whether there was an interaction
between wearing stockings and the effect of
time. Paired t-tests compared the circumference
of the ankle and calf before and after 120
minutes for the stocking and nonstocking leg,
and then for the difference between before and
after, for stocking use versus no use.
Power Calculation
A pilot study demonstrated a standard deviation
for paired differences in popliteal peak systolic
velocity of 1.3 cm/s, and the mean peak systolic
velocity in the seated position was around
3.5 cm/s.24 A difference of 20% was considered
to represent a significant difference in blood
flow. A sample size of 20 participants had 80%
power to detect a difference of 0.9 cm/s of peak
systolic velocity, using a paired t-test.
RESULTS
Out of the 20 participants who completed the
study, one subject withdrew due to fainting
after seeing the initial ultrasound image on the
monitor. A total of 63.2% of the participants
were female (n=12; male participants, n=7).
The characteristics of the participants are shown
in Table 1.
Variable Mean (SD) Median (IQR) Min to max
Age (years) 37.9 (9.7) 35 (30 to 43) 26 to 61
Height (m) 1.73 (11.6) 1.74 (1.65 to 1.80) 1.52 to 1.98
Weight (kg) 71.4 (11.6) 70 (61 to 82) 57 to 99
BMI (kg/m2) 24.1 (4.7) 22.7 (21.3 to 25.0) 19.9 to 39.7
Table 1. Characteristics of participants.
BMI= body mass index; IQR=interquartile range; SD=standard deviation.
Adv Ther (2011) 28(3) 5
The summary statistics for the outcome
variables are shown in Tables 2 and 3. At 120
minutes, the peak systolic velocity was 24%
higher with the stocking treatment, with a mean
difference of 0.34 cm/s (95% CI, 0.12 to 0.56,
P=0.004). The peak systolic velocity was also
significantly greater with stocking use, compared
with no stocking use, at 30 and 60 minutes. The
mean flow velocity and total volume flow were
greater at 60 and 120 minutes with stocking use,
Time (minutes)
Variable 0 30 60 120
Peak systolic velocity (cm/s)
Stocking
No stocking
2.4 (1.0)
2.1 (0.57)
2.2 (0.64)
1.9 (0.47)
2.3 (0.74)
1.9 (0.37)
2.1 (0.50)
1.7 (0.45)
Mean ow velocity (cm/s)
Stocking
No stocking
1.6 (0.62)
1.4 (0.46)
1.4 (0.36)
1.3 (0.27)
1.4 (0.44)
1.2 (0.27)
1.3 (0.30)
1.1 (0.33)
Total olume ow (L/min)
Stocking
No stocking
0.09 (0.036)
0.08 (0.026)
0.08 (0.029)
0.07 (0.029)
0.09 (0.035)
0.07 (0.025)
0.08 (0.025)
0.07 (0.020)
Vein area (mm2)
Stocking
No stocking
64.0 (19.0)
62.4 (15.5)
62.4 (17.5)
63.3 (16.9)
63.7 (20.6)
64.5 (17.8)
60.0 (17.6)
65.1 (16.8)
Table 2. Popliteal vein measurements according to stocking and no stocking treatments during the 120 minutes of seated
immobility. Data presented as mean (SD).
SD=standard deviation.
Time (minutes)
Variable 0 30 60 120
Peak systolic velocity (cm/s)
Mean (SD)
95% CI
P value
0.31 (0.75)
–0.05 to 0.67
0.084
0.29 (0.51)
0.05 to 0.53
0.022
0.47 (0.67)
0.15 to 0.80
0.007
0.34 (0.47)
0.12 to 0.56
0.004
Mean ow velocity (cm/s)
Mean (SD)
95% CI
P value
0.14 (0.40)
–0.05 to 0.33
0.150
0.12 (0.30)
–0.03 to 0.26
0.110
0.25 (0.38)
0.07 to 0.43
0.011
0.20 (0.27)
0.07 to 0.32
0.005
Total olume ow (L/min)
Mean (SD)
95% CI
P value
0.010 (0.030)
–0.003 to 0.026
0.110
0.007 (0.017)
0.000 to 0.015
0.070
0.017 (0.029)
0.004 to 0.031
0.017
0.007 (0.024)
–0.004 to 0.019
0.210
Vein area (mm2)
Mean (SD)
95% CI
P value
1.6 (15.9)
–6.1 to 9.3
0.67
–0.9 (16.6)
–8.9 to 7.1
0.81
–0.8 (17.6)
–9.3 to 7.7
0.84
–5.1 (19.1)
–14.4 to 4.1
0.26
Table 3. Dierences in popliteal vein measurements between stocking and no stocking treatment during the 120 minutes of
seated immobility.
CI=condence intervals; SD=standard deviation.
6 Adv Ther (2011) 28(3)
but there was no statistically significant difference
in vein cross-sectional area (Tables 2 and 3). Mixed
linear models confirmed these findings, with the
peak systolic velocity, mean flow velocity, and
total volume flow all significantly greater with the
use of stockings (Table 4). For both the legs with
the stocking and without the stocking there was
a gradual decline in these variables with time, but
the rate of decline was independent of whether
or not stockings were used (Figure 3). The peak
systolic velocity was 0.35 cm/s (95% CI, 0.22 to
0.49, P<0.001) higher with stocking use, using the
mixed linear model estimate.
There was a significant increase in the ankle
circumference by the end of the 120-minute
study period in the nonstocking leg of the
subgroup; the reduction in ankle circumference
in the stocking leg was not significant. The
overall difference in the baseline to 120-minute
endpoint measurement of ankle circumference
Table 4. Dierences in popliteal vein measurements between stocking and no stocking treatment analyzed by mixed linear
model.
Figure 3. e time course of peak systolic velocity in popliteal vein for stocking (dotted line) and no stocking (continuous
line) treatments.
Stockings minus no
stockings (95% CI)
Change per minute
(95% CI)
P value for stockings
time interaction
Peak systolic velocity (cm/s) 0.35 (0.22 to 0.49)
P<0.001
–0.0024
(–0.0044 to –0.0005)
P=0.019
0.77
Mean ow velocity (cm/s) 0.17 (0.10 to 0.25)
P<0.001
–0.0022
(–0.0035 to –0.0009)
P=0.003
0.46
Total olume ow (L/min) 0.011 (0.0054 to 0.017)
P<0.001
–0.001
(–0.0016 to –0.0003)
P =0.003
0.76
Vein area (mm2)1.2 (–2.2 to 4.5)
P=0.49
–0.004
(–0.042 to 0.034)
P=0.83
0.17
6
5
3
4
2
1
0
Time (minutes)
Peak systolic velocity (cm/s)
0 10 20 30 40 50 60 70 80 90 100 110 120
CI=condence intervals.
Adv Ther (2011) 28(3) 7
Variable (n=8 for all) Mean (SD)
Ankle
Nonstocking leg before 220.6 (13.0)
Nonstocking leg aer 225.0 (15.9)
Nonstocking leg aer minus before 4.4 (3.2)
Estimate (95% CI) 4.4 (1.7 to 7.1)
P value P=0.006
Stocking leg before 222.3 (13.2)
Stocking leg aer 220.4 (14.6)
Stocking leg aer minus before –1.9 (4.3)
Estimate (95% CI) –1.9 (–5.4 to 1.7)
P value P=0.25
Stocking leg aer minus before, minus nonstocking leg aer minus before –6.3 (6.0)
Estimate (95% CI) –6.3 (–11.3 to –1.2)
P value P=0.021
Calf
Nonstocking leg before 384.8 (28.0)
Nonstocking leg aer 397.3 (33.1)
Nonstocking leg aer minus before 12.5 (6.9)
Estimate (95% CI) 12.5 (6.8 to 18.2)
P value P=0.001
Stocking leg before 383.9 (24.6)
Stocking leg aer 388.5 (32.8)
Stocking leg aer minus before 4.6 (10.7)
Estimate (95% CI) 4.6 (–4.3 to 13.6)
P value P=0.26
Stocking leg aer minus before, minus nonstocking leg aer minus before –7.9 (6.5)
Estimate (95% CI) –7.9 (–13.3 to –2.4)
P value P=0.011
Table 5. Dierences in “aer versus before” measurements of ankle and calf circumference (mm) accordance to stocking and
no stocking treatments.
CI=condence intervals; SD=standard deviation.
between the stocking leg and nonstocking leg
was –6.3 mm (95% CI, –11.3 to –1.2, P=0.021)
(Table 5). There was a significant increase in
the calf circumference during the 120-minute
period in the nonstocking leg; the increase
in calf circumference in the stocking leg was
not significant. The overall difference in the
baseline to 120-minute measurement in calf
circumference between the stocking leg and
nonstocking leg was –7.9 mm (95% CI, –13.3 to
–2.4, P=0.011) (Table 5).
DISCUSSION
This study has demonstrated that the novel,
merino wool, below-knee graduated compression
8 Adv Ther (2011) 28(3)
stocking increases lower limb venous blood
flow during prolonged seated immobility. The
magnitude of the increase in popliteal vein peak
systolic velocity was similar to that observed
with other Class 1 and 2 graduated compression
stockings.18 A wide range of Class 1 and 2 below-
knee graduated compression stockings have
been shown to reduce the risk of VTE associated
with long-distance travel.25 As a result, it is
reasonable to conclude that the novel stockings
may be effective in reducing the risk of VTE
associated with prolonged seated immobility,
due to long-distance travel. The stocking was
also associated with a reduction in the swelling
of the leg at both the ankle and calf, which
suggests potential utility in lower limb edema,
secondary to chronic venous insufficiency and
lymphedema.
There are a number of methodological
issues relevant to the interpretation of the
study findings. We studied healthy participants
without previous DVT or PE to ensure that our
results were generalizable to the working public.
Doppler ultrasound was employed as a highly
sensitive, specific, and reproducible noninvasive
method of measuring lower-limb deep-vein
hemodynamics.26,27 The peak systolic velocity
was chosen as the primary outcome variable, as
it represents the most consistent nonartefactual
wave form detected by ultrasound. Participants
were instructed not to move their legs in
each position to provide a stable baseline
measurement, and to ensure that the findings
related to seated immobility. Although it has
been demonstrated that the right and left legs
have similar venous hemodynamics and vein
diameters,18,28 our participants were randomized
to the application of the stocking to either the
right and/or left leg, to avoid any potential
difference. As popliteal vein blood flow decreases
progressively over time,29 the measurements
were made over a 120-minute time period.
This also had the advantage of replicating the
situation of prolonged seated immobility. It is
known that small changes in a person’s seating
position can affect lower limb hemodynamics,
and for standardization, measurements were
made with the leg flexed to 120 degrees.
A limitation of the study is that it was
conducted in a research setting under controlled
conditions in healthy participants. As a result,
our findings may not be generalizable to
participants with venous or arterial disease, or
different body habitus. A further limitation was
that it was not possible to blind the sonographer
from the intervention allocation, due to the
requirement to undertake the ultrasound
examination of popliteal vein close to the upper
end of the stocking, and this may have biased
the results.
We note the lack of concordance in the
available literature of the magnitude of popliteal
peak systolic velocity reported when participants
are seated at rest. We observed a peak systolic
velocity of 2.1 cm/s without any compression
therapy, which contrasts with the findings
reported by Kalodiki et al.30 and Delis et al.,31
who reported peak systolic velocity values of
8.4 cm/s and about 6 cm/s, respectively. The
differences in peak systolic velocity values are
most likely explained by our strict requirement
that the participants kept their legs very still and
relaxed for the duration of the testing period.
However, we cannot rule out other relevant
variables that were technician dependent such
as ultrasonography measurement settings,
probe placement, orientation, and pressure,
or protocol related variables such as chair
design and material, clothing worn, participant
hydration, or environmental variables such as
ambient temperature.
The main finding was that wearing the
graduated compression stocking increased lower
limb venous hemodynamics, determined by
Adv Ther (2011) 28(3) 9
measurements of peak systolic velocity, mean
flow volume, and total volume flow in the
popliteal vein. The magnitude of the increase in
peak systolic flow was 24%, similar to the 26%
increase previously reported with a comparable
Grade 1 below-knee graduated compression
stocking.18 In contrast, there was no reduction in
vein cross-sectional area, which had been noted
previously.18
After the study started, we observed that
some participants developed swelling in the leg
without the stocking. To investigate this further,
we undertook a supplementary investigation in
a subgroup of participants who attended later in
the study, in whom ankle and calf measurements
were made before and immediately after the
stocking had been worn for 120 minutes. This
showed that there was a reduction in swelling at
both the ankle and calf in the legs with the use
of the stocking. Although the interpretation of
this observation was limited by the possibility
of bias, as the comparisons were based on
nonblinded measurements, it does suggest
that the stockings may have utility in reducing
lower limb edema associated with lymphedema
and chronic venous insufficiency, including
varicose veins and venous ulcers. Our findings
are consistent with previous observations
that below-knee compression stockings with
a pressure range of between 11 and 22 mmHg
are able to reduce or totally prevent edema
developing during the working day.32
Prolonged seated immobility during either
work or travel is now the most common risk
factor for DVT and PE in the New Zealand
population.3,4 As venous stasis is the most
important factor contributing to the risk of DVT
and/or PE with prolonged seated immobility, the
increase in lower limb venous blood flow with
this compression stocking would suggest that
its use may reduce the risk of DVT and/or PE in
this situation. In support of this view, it has been
shown in clinical trials that similar below-knee
graduated compression stockings reduce the risk
of DVT with long-distance air travel by about
90%.25
CONCLUSION
In view of these findings, it would be
reasonable to recommend the use of the novel
merino wool, Grade 1, below-knee graduated
compression stockings to reduce the risk of VTE
in situations of prolonged seated immobility,
such as long-distance travel. Their use can also
be recommended to reduce VTE risk in other
situations associated with immobility, such as
in the hospital setting with a medical illness,
or following surgery.20 The study findings also
suggest that this stocking can be used to reduce
lower limb edema secondary to chronic venous
insufficiency and lymphedema.
ACKNOWLEDGMENTS
This study was funded by a research grant from
The Merino Company (New Zealand). The
authors declare no conflict of interest.
Thomas Charles is the named guarantor
author responsible for the integrity of the work.
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