1. i
The clinical significance of calf vein
deep vein thrombosis
NICE guidelines for VTE, are they best practice?

2. ii
Table of contents
Introduction and background ………pg. 1
Aim ………pg. 1
Literature search strategy ………pg. 2
NICE Guidelines and evidence based practise ………pg. 2
Defining distal DVT ………pg. 3
A general consensus, to treat or not to treat ………pg. 3
A case for stratification of scanning and treatment protocols ………pg. 5
Patient outcome, the heart of the matter ………pg. 6
Post Thrombotic Syndrome (PTS) ………pg. 7
Local perspective, utopia and compromise ………pg. 8
Conclusions and recommendations ………pg. 9
References ………pg. 10
Bibliography ………pg. 13
Appendix A ………pg. 14
Appendix B ………pg. 17
Appendix C ………pg. 25

3. 1
Introduction and background
Controversy surrounding the value of performing ultrasound examination of the calf
veins for diagnosing deep vein thrombosis (DVT) still exists (Righini, 2007 &
Schellong, 2007). In June 2012 the National Institute of Clinical Excellence (NICE)
published guidelines for the management of venous thromboembolic diseases
(NICE, 2012). They summarised that “ultrasound techniques are effective for ruling
out proximal DVTs but not calf vein or distal DVTs” (NICE, 2012 p.52). Their
evidence suggests that compared to reference levels (venography) ultrasound of the
distal veins has a sensitivity of just 29% (NICE, 2012). Despite these guidelines a
recent study by Shahi and Murali (2013) identified that 68% of health-care
professionals trained in vascular ultrasound scanned the whole leg routinely. They
also found that all accredited vascular scientists in their study scanned the whole leg
routinely. This is in accordance with the performance guidelines for the assessment
of DVT published by the Professional Standards Committee of the Society for
Vascular Technology (SVT) (2012).
Current protocol at the hospital at which the author is employed is to scan the entire
leg reducing the need for a re-scan in the event of a negative ultrasound test result
and positive D-dimer test. The majority of DVT examinations are referred through the
Urgent Care Centre (UCC) outpatient pathway. Any form of identified calf vein DVT
(CDVT) is treated with anticoagulation. This study is relevant as the local standard
operating procedure for assessment of DVT is due for review in June 2014 and
current protocol is not in accordance with NICE guidelines.
Aim
This review will aim to evaluate findings regarding the clinical significance of
performing ultrasound examination of the calf veins and identifying and treating
CDVT.

4. 2
Literature search strategy
An initial search was performed using Library Plus. Relevant articles were identified
and scanned for keywords. A full search of Library Plus was then performed. Four
searches produced 2,031,454 hits, these searches were combined to produce a
result of 68 articles. Articles published in a language other than English were
excluded, as were articles published prior to 2009. 2009 was chosen as the cut off
as this was the latest evidence (Gibson et al.) reviewed and referenced within the
NICE guidance and because the aim of this review is to provide an up to date
perspective on the topic. These exclusions left 16 articles. These were filtered for
inclusion and relevant articles were then extensively cross referenced. It would have
been preferable to only include and review randomised controlled trials (RCT),
however in this date range that would have left just Schwarz et al. (2010). It was
decided to include the RCT of Bernardi et al. (2008) to add strength to the review.
Therefore, prospective (5) and retrospective (4) studies and four pertinent meta-
analyses and systematic reviews were also included to make a total of 15 articles
that were reviewed. The search strategy is included in appendix A. Major findings of
each article reviewed are tabulated in appendix B.
NICE Guidelines and evidence based practise
In creating the guidelines the rationale for only scanning proximal veins of the leg
was based on the findings of three studies. Gibson et al., (2009) found little
difference in patient outcome between a group undergoing complete leg ultrasound
examination and those undergoing a proximal leg veins only technique with a repeat
examination for those with a negative first examination. They concluded that both
strategies were equally valid. This outcome was reflected in the work of Bernardi et
al. (2008) who’s study stated that complete examination offered a one day answer
but was harder to perform and may result in more patients receiving unnecessary
anticoagulation therapy, whereas the proximal vein only technique was simple to
perform but required follow up examination in approximately a quarter of their
sample. Finally, Goodacre et al., (2006) was a large meta-analysis including 100
cohorts but only research published to 2004. Results suggested that the evidence for
use of a repeat proximal veins scan technique was based on the findings of

5. 3
observational studies identifying that 1.3% of repeat scans will be positive, but they
summarised with the caveat that ‘Use of ultrasound requires a strategy for managing
possible distal DVT or a conviction that these DVT are of little pathological
significance’ (2006 p.39).
Guidelines should be firmly anchored in rigorous evidence based practise. NICE
(2012) acknowledge that the quality of the evidence is of low to moderate quality, yet
these were deemed sufficient to base the guideline on.
Defining distal DVT
One issue of contention within the literature is what constitutes distal DVT. Pengas et
al, (2013) found little agreement as to whether muscular vein thrombosis (MVT)
(thrombosis of the muscular veins i.e. the gastrocnemius and soleal veins) should be
classified as superficial or deep and therefore whether it deserved treating as DVT or
not. Patients may face a lottery on treatment depending on the significance of MVT
to a centre, and whether the centre treats MVT as DVT. Sales et al., (2010) found
much of their literature failed to distinguish between distal DVT and MVT, an
example being Palareti et al., (2010) who use the term ‘Isolated Calf DVT’ but fail to
clarify what this includes. Parisi et al., (2009) and Bernardi et al., (2008) identified
that there was no significant differences in the progression rates between MVT and
tibio-peroneal DVT suggesting the same treatment for these thrombi is justified.
Trust policy at the author’s place of work is to treat MVT as per DVT. For the
purpose of this review MVT and distal DVT will be given the same significance.
A general consensus, to treat or not to treat
Bernardi et al., (2008) and Gibson et al., (2009) were the only research comparing
the effectiveness of a whole leg ultrasound scan versus a proximal veins technique.
With the exception of two studies, all other research reviewed began with methods
that already identified CDVT and then watched its progress against a treatment
group to examine the differences. Most used end points such as proximal
propagation and pulmonary embolus to determine significance. The two exceptions
were Sevestre et al., (2009) and Johnson et al., (2010), they sought to determine

6. 4
whether anticoagulation could be safely withheld in patients with a single negative
whole leg ultrasound scan. Appendix C provides a general overview of how the
authors view the clinical significance of CDVT based on their own outcomes.
Whether they feel it is necessary to scan the calf veins and identify CDVT has been
assumed by the results and conclusions of each study.
Three articles reviewed expressed definitive favour for treating CDVT with
anticoagulation therapy. In their retrospective study Lautz et al., (2009) found
statistical significance comparing incidence of subsequent venous thromboembolic
events (VTE) in groups of patients receiving therapeutic anticoagulation with those
receiving no treatment or prophylactic treatment. The therapeutic treatment group
had a VTE incidence of 12% compared with 30% and 27% in the groups with no
treatment and prophylactic treatment respectively (p=0.0003). Resolution of CDVT at
follow up was also found to be higher in the treatment group. These results may
have been skewed by the large number of ambulatory low risk patients represented
in the treatment group possibly being less predisposed to having a VTE event.
Kret et al., (2013) found similar results. In their treatment group 65% had complete
resolution at the follow up scan compared to just 21% who were given no treatment
or prophylactic anticoagulation. Their study had weaknesses. It was retrospective,
excluding patients without multiple follow up scans. It could be argued that those
included were more prone to VTE events and that is why they needed multiple follow
up scans. Likewise, excluded patients may have had spontaneous resolution and not
needed a follow up. Statistically their findings also need to be placed in perspective.
They stated that at follow up 25% of their patients had either propagation of
thrombus or a new thrombus at a remote site. However, over a period where 7283
lower extremity venous duplex exams were performed, that 25% of 57 patients with
CDVT represents less than 0.2% of all scans undertaken. However, of nine patients
in their study who developed a pulmonary embolism (PE) none were taking
therapeutic anticoagulation at the time of diagnosis and they therefore concluded
that CDVT warrants therapeutic anticoagulation.
De Martino et al., (2012) stated that the ‘quality of evidence to support
anticoagulation for reduction of thrombus propagation is adequate’ (p.235). They
found a link between therapeutic anticoagulation for CDVT and reduced proximal

7. 5
propagation and PE. They stated that their reviewed literature was based on studies
with small sample sizes. Additionally the researchers used the reviewed literature to
attempt to answer questions these studies were not specifically designed to answer.
Contrary to these results Sales et al., (2010) found no difference in the rate of
thrombus propagation when comparing a group of patients undergoing
anticoagulation therapy for CDVT and a group with no treatment. This outcome was
reflected in the RCT of Schwarz et al., (2010). They found no significant difference in
propagation between a group receiving therapeutic anticoagulation and compression
stocking therapy and a group just using the compression stockings. However their
sample was 89% outpatients and mostly ambulatory and therefore not generalizable
to higher risk patient groups.
Gibson et al., (2009) and Bernardi et al., (2008) were not in favour of routine
anticoagulation therapy speculating that though a whole leg scan discovers CDVT it
may also lead to unnecessary treatment and therefore ‘detecting isolated calf vein
DVT may not be as relevant as previously believed’ (Bernardi et al., 2008 p.1657).
Sule et al., (2009) in a small study of 51 patients was also in favour of surveillance
scans to detect significant propagation.
Pengas et al., (2013) were not in favour of routine anticoagulation therapy pointing to
a well-documented risk of haemorrhage in their sample of orthopaedic patients with
CDVT. Though Masuda et al., (2012) found no compelling evidence for routine
anticoagulation therapy they did note that proximal DVT is universally treated with
anticoagulation with seemingly little obvious concern for bleeding issues and
therefore couldn’t understand the controversy over anticoagulation for CDVT.
Between the studies there is no real consensus as to whether anticoagulation
therapy should be routine. The one recurring agreement is that the rules are different
for patients in higher risk groups.
A case for stratification of scanning and treatment protocols
Rates of proximal propagation of CDVT have been found to be as high as 25%
(Lagerstedt et al., 1985). Many of the reviewed articles identified that patients in a
high risk group (those with malignancy, hospitalised, bed bound or with unprovoked

8. 6
CDVT) may benefit from anticoagulation therapy. Parisi et al., (2009) commented
that 80-90% of patients probably do not need anticoagulation therapy, the challenge
is identifying the 10-20% that do. Their results found that proximal propagation was
always associated with unprovoked DVT. They recommended treating with
prolonged anticoagulation therapy. Masuda et al., (2012) and Sales et al., (2010)
demonstrated links between CDVT propagation and malignancy. These results
resonate closely with the findings of Singh et al., (2012). In their prospective study
they found that 7% of their sample had proximal propagation of CDVT. All were high
risk group patients. They also found that 43% of their sample had persistent
thrombus but without propagation. This may indicate that in lower risk patient groups
the risk of proximal propagation is less and anticoagulation may not be routinely
necessary. They also found that all propagations that occurred were found on the
follow up scans between 1 and 3 months. Therefore a single follow up scan 6-8 days
after a negative proximal scan as per NICE (2012) guidelines may not be sufficient
time to identify all the significant CDVT that propagate. They concluded that high risk
patients may need immediate anticoagulation therapy whereas low risk ambulatory
patients could be safely observed with ultrasound.
In their small sample RCT Schwarz et al., (2010) advocated an ‘individual approach’
(p.1248) to treatment where each case is treated according to the individual’s
situation. They stated the probable need for anticoagulation in high risk patients.
These results are complemented by the findings of Johnson et al., (2010) and
Sevestre et al., (2009). The three studies all felt anticoagulation therapy could be
withheld in low risk ambulatory patients.
The evidence points to the potential for stratified treatment according to identified
patient risk group on identification of CDVT. All patients with CDVT cannot be
generically treated since risk factors appear to have a bearing on outcome.
Patient outcome, the heart of the matter
In their summary of research recommendations NICE concluded that an ‘RCT with
cost-effectiveness analysis could answer the crucial question of whether full-leg
ultrasound improves patient outcomes and allows for more effective use of NHS
resources’. (NICE, 2012 p.267). If the sole purpose of the examination is to rule out

9. 7
significant DVT then the proximal vein only technique recommended by NICE (2012)
may be sufficient. However, Gibson et al., (2009) and Bernardi et al., (2008) on
whose evidence the guidelines were based used 94% outpatients and outpatients
from the emergency department or primary care pathways respectively as their
sample. As has been shown previously, these samples and patient types may not
represent the full spectrum of patients at risk from developing proximal DVT from
CDVT. Additionally, as practitioners with our patients’ best interests at heart is it
sufficient to simply rule out DVT when there is the potential there to diagnose other
causes? Moody and Hafner (2009) identified a pooled DVT incidence of 19% in their
sample. Palareti et al., (2010) estimated the rate of DVT positive scans to be 25%.
Sevestre et al., (2009) made a valid point in that of 2848 patients in their study
scanned for DVT 23.6% were found to have an alternative cause.
Lohr and Fellner (2010) found that a proximal only technique with follow up scans is
less cost effective than a single whole leg scan. They found patients to be frequently
non-compliant in attending follow up scans. Mcilrath et al., (2006) found similarly low
rates of return for follow up scans. Despite the added time concerns with a whole leg
scan Schwarz et al., (2002) found this to be only an additional 4 minutes per calf.
Gibson et al., (2009) identified that a whole leg technique had a low rate of
inconclusive scans and offered the patient a one visit only experience.
Post Thrombotic Syndrome (PTS)
Proximal DVT is associated with development of PE but avoiding fatality in the short
term does not exclude long term issues associated with DVT. Kahn and Ginsberg
(2002) and Guanella (2013) showed that CDVT is not free of embolic risk and can
trigger PTS. Cowell et al., (2007) stated that CDVT may be significant ‘because of its
recognised association with post-phlebitic syndrome’ (p.861). Lautz et al., (2009)
found that 90% of patients receiving anticoagulation therapy for CDVT remained free
of VTE events 2 years after their initial diagnosis, suggesting anticoagulation was
linked to a reduced rate of further VTE events. Their sample was a mixture of high
and low risk patients. Furthermore Sales et al., (2010) found ‘no haemorrhagic
complications in the therapy group’ (p.1254) stating that this may refute the
argument that anticoagulation is associated with significant bleeding risk. One

10. 8
concern with a proximal only technique is that regardless of origin there is only scope
for finding proximal DVT. The whole leg technique gives the clinician the option to
treat before CDVT becomes proximal DVT. The longer term outcomes for the patient
must be weighed against the practicalities of the scanning method used.
Local perspective, utopia and compromise
Sule et al., (2009) recommend rescan at one week one month and three months.
Bernardi et al., (2008) noted that 30.9% of their patients needed re-scheduling for a
follow up scan. From a local perspective it would be unrealistic to perform this
amount of follow up scans while trying to stay current with acute cases needing their
first investigation. This viewpoint may be reflected elsewhere in the country with one
consultant radiologist in a rapid response letter to the BMJ calling the NICE
guidelines timeframes utopian (Makowska-Webb, 2012). The authors’ department
relies on an accurate whole leg scan technique aimed at discovering all DVT and
thereby negating the need for a follow up scan where possible, however, not
everyone performing a DVT scan will have the skill and training of a vascular
sonographer. The authors’ viewpoint is that NICE (2012) have created a set of
guidelines that will provide in most cases an immediate answer from a technique that
can be learnt quickly by practitioners. This may not be thorough or suitable for all
patients but it is achievable, repeatable and auditable. The SVT (2012) guidelines
assume that all practitioners are capable of scanning the calf veins to a high
standard. NICE (2012) have disregarded completely the need to scan the calf veins.
A compromise could be found in the guidelines of the American Institute of
Ultrasound in Medicine (AIUM). They recommend a standard examination of the
proximal leg including compression, colour and spectral techniques. If the cause is
not found from this examination and there are focal symptoms they recommend
examination of the symptomatic region. (AIUM, 2011). Similarly, the American
College of Chest Physicians (Kearon et al., 2012) altered their guidelines. In 2008
they recommended routine anticoagulation therapy for all CDVT (Kearon et al.,
2008), the 2012 guidelines suggest that only patients with ‘severe symptoms or risk
factors for extension’ (Kearon et al., 2008 p.420s) should receive anticoagulation
therapy.

11. 9
Conclusions and recommendations
In general the quality of recent research is at best moderate with most studies having
serious flaws. Twelve of the fifteen studies pointed to the need for further in-depth
RCT to enlighten current practise. The quality of evidence was certainly a limitation
of this review. Additionally, current trust protocols to scan the whole leg routinely
may have had influence on the authors’ perspective and an element of bias in favour
of a whole leg technique cannot be ruled out.
Within this review only three of fifteen articles found in favour of routinely treating
CDVT. Two (the articles used as evidence in the NICE guidelines) concluded that a
proximal veins only scan with repeats had similar patient outcomes as a whole leg
ultrasound but led to less patients undergoing potentially unnecessary treatment.
The remaining articles varied in the degree of significance placed on CDVT. Most
stated that routine anticoagulation is not necessary except in certain patient types.
The key recurring theme was that high risk group patients were almost always
associated with CDVT propagation to the proximal veins. This finding strengthens
the case for a stratification process whereby high risk patients always get a full whole
leg scan. With high risk being associated with proximal propagation it should be a
duty of care to diagnose at the earliest point and begin treatment if appropriate at the
earliest point.
Another theme also showed that a flexible approach to treatment should be a
consideration and that although guidelines limited by cost effectiveness and
simplicity of implementation are auditable and may account for the majority, health
care is about doing the best you can by every patient, not shoehorning all patients to
fit a single process.
The authors’ personal view is that the guidelines are a compromise between skill and
practicality. The majority of patients will not need more than a single proximal leg
scan. For others finding and treating CDVT at the earliest possibility is probably
essential. The sonographer can only attempt to find the cause of the patients’
symptoms. However guidelines are not rules and ultimately, at a local level the
significance of CDVT and the risk of beginning anticoagulation therapy versus the
risk of developing a proximal DVT will depend on the viewpoint of the referring
clinician.

12. 10
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know and what we are doing. Journal of Thrombosis and Haemostasis. 10 (1) pp.
11

16. 14
Appendix A.
Literature search strategy results
Search
ID#
Search Terms Search Options Last Run Via Results
S1
AB calf vein OR AB
distal OR AB
thrombus OR SU calf
vein
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638,306
S2 SU ultras*
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1,306,872
S3
AB distal extremity
OR AB calf vein OR
SO calf vein
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16,941
S4
AB deep vein
thrombosis OR AB
dvt OR TI dvt OR
AB calf vein
thrombosis
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69,335

17. 15
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S5 S1 AND S2
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22,237
S6 S3 AND S5
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1,002
S7 S4 AND S6
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494
S8
( S4 AND S6 ) AND
TI calf
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68

18. 16
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S9
( S4 AND S6 ) AND
TI calf
Limiters - Date Published:
20080101-20131231
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19
S10
( S4 AND S6 ) AND
TI calf
Limiters - Date Published:
20080101-20131231
Limiters - Language
English
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16

19. 17
Appendix B.
Summary of reviewed articles and key findings.
Glossary of abbreviations
Abbreviation Full Abbreviation Full Abbreviation Full
VTE Venous
thromboembolism
IGSVT Isolated
gastrocnemius or
soleal vein
thrombosis
RCT Randomized
controlled trial
CUS Cereal ultrasound MVT Muscular vein
thrombosis
ICDVT Isolated calf deep
vein thrombosis
Ca Cancer ICVT Isolated calf vein
thrombosis
DVT Deep vein
thrombosis
PE Pulmonary embolism ATV Anterior tibial vein US Ultrasound
ED Emergency
Department
Author/Year Sample size
(n)
Study type Population
Type
Topic Study
limitations
Conclusions Recommendations Statistics Comments
Kret et al.,
2013
57 patients Non randomised
retrospective
review of a
vascular lab
database
Not specified
but must have
had a follow
up US scan to
be included
Rates of VTE
progression and
resolution,
effects of
anticoagulant
therapy in
patients with
IGSVT.
Small sample
size.
Retrospective,
uniform follow
up not possible.
Selection bias
from only
including
patients who
had a follow up
scan.
IGSVT is
associated with
significant VTE
progression,
therapeutic
anticoagulation is
associated with
resolution.
Untreated patients
with IGSVT should
be monitored with
follow up scans.
P< .002 that
resolution was
attributable to
therapy but
this was based
on findings
from follow up
scans, mean
follow up was
113 days but
the range was
2 – 1505 days,
can we expect
resolution after
Sample size is very small
to be drawing statistical
conclusions. Only take
into account those with a
follow up scan, there
must be a reason that
others with confirmed
IGSVT did not have a
follow up scan ? resolved
on its own? This would
significantly skew the
overall figures. There
was no standardised
treatment protocol, so

20. 18
2 days? And in
some patients
it might be
expected that
after 1505
days a clot
may have
resolved
without the
need for
therapy.
difficult to comment on
the effectiveness of
treatment.
Pengas,
2013
N/A Literature review Orthopaedic
patients
Does below
knee IGSVT
warrant
investigation
and treatment?
Only as strong
as studies being
reviewed.
Lack of
consensus in
answering the
question and lack
of solid evidence
solely from
orthopaedic
groups.
MVT should not
be routinely
treated but
observed with
CUS and treated if
found to have
propagated
RCT or further
scientific study to
indicate whether
treatment and
investigation of
IGSVT is warranted
in these patients
None
attempted.
Difficult to draw any
meaningful conclusions
from this limited work.
Singh et al.,
2012
156 patients
180 Limbs
Prospective
experimental
trial.
Mixed
patients, any
patient with
suspected and
ultrasound
confirmed
ICDVT 35%
outpatients.
Lysis of clot,
incidence of
propagation to
proximal veins
and pulmonary
emboli.
Non-
randomised,
convenience
sample, single
centre study,
Figures suggest
no subjects
were lost to
follow up over a
course of
potentially 8
months.
ICDVT can be
safely observed in
asymptomatic
patients, High risk
groups of patients
(Ortho, Ca, etc.)
recommended
anticoagulation
therapy until
resolved or
ambulant.
Large randomized
control trial needed
to identify the best
treatment for sub-
groups of patients
e.g. Orthopaedic
patients.
Used
descriptive
statistics only,
probably
appropriate
given small
sample size
and mixture of
sub-groups
involved.
At 1-3 month follow up
the patients with
propagation of ICDVT
were all from a high risk
background i.e. CA
patients, immobile or post
orthopaedic surgery.
There is confusion over
which patients received
therapeutic doses of
anticoagulation, who
received prophylactic and
when this occurred.
Difficult to draw any
meaningful conclusion
from this study beyond
the actual sample.

21. 19
De-Martino
et al., 2012
N/A Meta-analysis Varied
according to
included
studies.
Assess efficacy
and safety of
anticoagulation
therapy for adult
patients with
isolated calf vein
DVT
Only as strong
as the data
being analysed,
failure of
included studies
to analyse the
full spectrum of
treatment
benefits and
harms makes
objective
assessment by
meta-analysis
difficult. Included
studies were not
designed to
answer the
meta-analysis
question. Lack
of relevant
studies to
perform a full
meta-analysis
Found that
included studies
were mostly of low
methodological
standard. Issues
with the RCT’s of
blinding and
sequence
generation leading
to less confidence
in the outcomes.
Anticoagulation
therapy for CDVT
significantly
reduces proximal
propagation.
No comment
made on anti-
coagulation
therapy effect on
PE, death etc.
Rigorous RCT is
necessary to further
enhance current
practise
P=0.001 for
rates of
thrombus
propagation to
the proximal
vein, this
compares anti-
coagulated
patient
outcome to
control
patients that
received no
treatment,
however there
were
significantly
more patients
in the control
group than the
treatment
group (93
treated 326
not treated)
difficult to draw
meaningful
conclusion.
Acknowledged that the
methods of the analysed
studies were mostly poor.
Pooled studies were not
like for like, some dealt
with ambulatory patients
and one with mixed,
difficult to make
assumptions based on
different sub-groups of
patients. Some studies
made the diagnosis of
CDVT by venography
and others by US, is
there a potential
difference in the
sensitivity of these
methods that may lead to
over/underreporting of
the true number of
positives?
This review used data
from research to answer
questions that the initial
research was not
purposefully designed
for.
Masuda et
al., 2012
N/A Systematic
review
Varied
according to
included
studies
Ultrasound
observation vs
anti-coagulation
for CDVT
Lack of
evidence to
perform a full
meta-analysis.
Only as strong
as the studies
being reviewed.
In the absence of
solid scientific
evidence either
option i.e.
surveillance or
anticoagulation
should be sought.
Doing nothing
should not be an
option.
Need for further well
designed and
adequately powered
studies to enlighten
further
Descriptive
statistics only
used.
Studies that are reviewed
are not all designed to
answer this question.
Schwarz et
al., 2010
107 patients Randomized
Controlled study
89%
outpatients
11% inpatients
Compare
efficacy and
safety of
anticoagulation
for CDVT vs
compression
therapy alone
Small numbers,
not
representative of
cross section of
patients, only
11% were from
higher risk
groups for DVT
Neither method
anticoagulation
nor compression
alone showed as
superior, in an
acknowledged low
risk patient group.
High risk patient
Individual treatment
depending on
findings, for low risk
patients US scan 1
week post
diagnosis,
anticoagulation
therapy for patients
with proximal
There appears
to be
reasonable
statistical
conclusions
drawn with no
extreme
conclusions
drawn from
Agreed through pilot and
consensus the protocol
for examination.
Appears to be a quite
well thought out study but
with some weaknesses
that could potentially
skew the figures.

22. 20
i.e. hospitalised,
active Ca etc.
Once
randomized
patients who
had been
prescribed
prophylactic
heparin for other
reasons were
permitted to
continue this
treatment. There
is no mention of
how many of
these patients
were included in
the study
groups cannot be
commented on by
this study.
progression.
In high risk groups
immediate
anticoagulation
therapy for at least
4 weeks.
what is quite a
small sample. May have been better to
just examine outpatients
or those at low risk of
VTE events as it is there
is no mention of the prior
risk factors in those
patients that had a
propagation. Could it be
more expected in certain
types of patient?
Johnson et
al., 2010
4731
patients from
pooled
studies with
negative
whole leg
CUS
Systematic
review and
meta-analysis
Various
according to
studies mostly
ambulatory
with a small
amount of
inpatients
Assessment of
safety of
withholding
anticoagulation
in patients with a
single negative
CUS by
estimating the
incidence of
VTE in the 3
months following
a negative test
result
In a mix of
studies there is
likely to be a
difference in
compression
ultrasound
technique.
Of limited value
for generalizing
to populations
not well
represented
within this study
e.g. active Ca,
pregnant etc.
The individual
studies had their
own exclusion
factors for
example one
chose to
exclude patients
with high pre-
test probability
possibly leading
Withholding
anticoagulation
after a negative
whole leg CUS
has a low failure
rate in patients
from a primarily
ambulatory
background and is
associated with
low risk for VTE in
the following 3
months post
negative test
result
Further studies into
the use of single
whole leg CUS for
patients with a high
pre-test probability
are needed.
No obvious
statistical
issues.
General impression a
good piece of work, few
flaws. Analysed research
not specifically designed
to answer the meta
analysis question.
Strategies implemented
in articles to reduce risk
of selection bias.
Difficult to generalize to a
population as most
patients came from an
ambulatory back-ground.
Studies were only traced
for follow up for 3 month
period

23. 21
to under-
reporting of
incidence in a
true
representative
cross section of
patients.
Sales, 2010 141 patients Retrospective
review of
medical records
Hospitalised
patients
Compared
effectiveness of
treatment vs non
treatment
through anti-
coagulation of
patients with
IGSVT through
measurement of
thrombus
progression
Retrospective
design, single
centre, limited
generalizability.
Sample were all
inpatients and
therefore more
likely to develop
DVT may lead to
over reporting of
cases
There was no
standard
treatment
protocol for the
therapy group of
patients.
In the absence of
thrombus
propagation
anticoagulation
cannot be
recommended
from the results of
this study.
RCT is needed to
investigate fully the
necessity of
anticoagulation
treatment for IGSVT
patients.
Descriptive
statistics
performed plus
some
statistical
testing with
strong
confidence
levels in the
results.
Lack of standard
treatment protocol in the
therapy group. Some
interesting findings but
some study weaknesses.
Limitations were stated
and conclusions are not
overly exaggerated.
Palareti et
al., 2010
431 out-
patients
Prospective,
blinded, 2 centre
study
Symptomatic
outpatients
fulfilling criteria
of not having
proximal
thrombosis on
a proximal U/S
scan
Investigation of
the
complications
rate of untreated
CDVT. Anti-
coagulation was
withheld from a
group of patients
with a possible
CDVT.
Small numbers
and only 2
centres,
therefore limited
generalizability.
All patients were
issued with
compression
stockings which
in itself is a form
of treatment.
This may lead to
under-reporting
of the true
outcome rate.
ATV’s were not
scanned.
Patients were
not all
Untreated CDVT
has an uneventful
clinical course at 3
month follow up,
The rate of
complications at
three was
significantly higher
in those with
CDVT.
Need for clinical
studies to identify
those symptomatic
patients in need of
investigation and
treatment.
Clinical relevance of
CDVT should be
decided by
specifically
designed,
multicentre,
prospective studies
with larger samples.
Good example
of how small
numbers in
studies can
significantly
skew statistical
figures, 2
DVT’s
discovered
due to
proximal
extension
made a
difference from
P number of
0.003 to
P.0.049 when
just 2 patients
are excluded
with dubious
findings.
Selection bias possible,
Does not state whether
all the examining
sonographers were
following the same
protocol for scanning the
calf veins, just that they
were experienced.
Looking at the statistics,
feel you can only draw
limited conclusions from
this work. Larger
numbers needed to make
it worthwhile and
generalizable beyond this
group of patients.

24. 22
consecutive
patients
elements of
selection bias
cannot be ruled
out.
Proves need
for a larger
sample.
Lautz et al.,
2009
406 patients Retrospective
review of
medical records
Mixed
inpatients and
outpatients.
Determine
incidence of
IGSVT and
determine the
effect of anti-
coagulation on
VTE events in
patients with
IGSVT.
Retrospective
design.
Results may
have been
skewed by the
number of low
risk patients
examined in one
group. May have
led to under-
reporting of true
number of
events from this
group.
Large numbers
(296) were lost
to follow up and
were
subsequently
excluded from
the study.
Therapeutic anti-
coagulation
significantly
decreased the
rate of VTE
events and
increased the rate
of IGSVT
resolution in this
study.
A randomized
control trial is
needed to evaluate
the risk vs benefit of
therapeutic anti-
coagulation for
IGSVT.
Statistical
analysis
showed a link
between
therapeutic
anticoagulatio
n and IGSVT
resolution but
numbers in the
study were
small and
different types
of
anticoagulant
were used to
treat not a
standardised
drug or dose.
Retrospective design
only dealt with muscular
vein thrombosis not all
deep calf veins.
Sule et al.,
2009
51 patients Retrospective
analysis of
medical records
Origin not
apparently
stated
Determine
whether
treatment for
CDVT with
anticoagulation
vs no treatment
affects patient
outcome
Very small
numbers,
retrospective
design, single
centre therefore
only
generalizable to
this set of
patients.
No mention of
risk group for
patients
CDVT may not
need treatment
with anti-
coagulation.
However if
symptoms worsen
or the CDVT
extends
proximally then
anti-coagulation is
recommended.
No
recommendations
Descriptive
only, too small
a sample to
draw
meaningful
conclusions
Recommendation
suggests follow up
surveillance scans at 2
weeks 1 month and 3
months. How feasible is
this at most NHS
hospitals with finite
resources?
Parisi et al.,
2009
171
outpatients
after
exclusions
Appears to be
prospective, but
the sampling
method is
Outpatients
only
Assessment of a
particular
treatment
regimen for
Small numbers
Only covers a
sub-group of the
2.9% of patients
had a progression
of thrombus to the
proximal veins.
No
recommendations
Descriptive
statistics only.
Uncertainty due to
absence of information
on methodology is a
shame because the

25. 23
unclear. those with
CDVT
people who may
develop a DVT.
Outpatients are
probably at a
lower risk than
immobile
inpatients. This
could lead to
potential under-
reporting of the
condition.
No control
group.
Most progressions
occurred in
patients with
unprovoked
CDVT.
Prolonged
treatment may be
pertinent in
patients with
unprovoked CDVT
research appears to have
produced a potentially
useful set of data.
Unclear on the sampling
method? Therefore
cannot rule out possible
sample bias.
Some exclusions due to
loss at follow up.
Sevestre et
al., 2009
3871
reduced to
1254
randomly
selected for
the follow up
study.
Prospective
multi centred
cohort study
Ambulatory
patients with
suspected
DVT
Determine the
safety of
withholding
anticoagulant
therapy from
patients with a
negative whole
leg U/S scan.
Not all patients
were followed
up.
Only looked at
ambulatory
patients with a
negative first
scan, Other
patient sub-
groups e.g.
pregnant women
or Ca patients
may need
further
investigation.
Episodes of fatal
PE may be
under-reported,
no autopsies
were carried out.
In ambulatory
patients (not
including certain
sub-groups)
anticoagulation
therapy can be
safely withheld
following a single
negative whole
leg U/S
examination.
Further study
necessary to
assess risk of
withholding
anticoagulant
therapy from higher
risk patient sub-
groups.
Statistics are
easy to
understand
and flow
charts make
the data
straightforward
to take in.
They don’t try
and draw too
much from
their figures
and remain
focussed on
the research
question.
Ambulatory outpatients
probably one of the lower
risk groups for DVT
complication.
Used a standardised
examination protocol and
the sample is a good
size. Shame not all
patients were followed
up. Issue with follow up in
that some were by phone
call and not necessarily
with the patient,
sometimes the DR or a
relative of the patient.
Use of 255 certified
sonographers from
across the country could
be seen to add
generalizability to the
research.
Gibson et
al., 2009
1002
patients
reduced
after
exclusions to
264 who
underwent
whole leg
Multi centre
Prospective
management
study with
elements of
randomisation in
patient selection
94%
outpatients
Compared the
safety and
feasibility of two
ultrasound
examination
methods, whole
leg US and CUS
Certain patient
types were
excluded
including.
pregnant
patients,
expected low
compliance,
Both methods are
comparable in
safety and
efficiency, CUS
has the drawback
of needing a
second scan
where whole leg
RCT is needed to
assess usefulness
of anticoagulant
therapy for
symptomatic CDVT
Used
appropriate
testing.
Statistical
conclusions
enforce
findings with
confidence.
Research acknowledges
some small flaws in
design but multi centred,
multi country
involvement, randomised
patient samples, the
methodological approach
appears sound and is

26. 24
US and 257
who
underwent
rapid
proximal
vein only US
ongoing
anticoagulants
therefore only
generalizable to
certain patient
groups and
mainly refers to
outpatients
Open design
modest sample
sizes
may lead to
potential over-
treatment
probably reasonably
generalizable to a wider
group of outpatients.
Bernardi et
al., 2008
2098 Randomized
controlled trial,
Outpatients
from an ED or
Primary care
referral
pathway
Comparison of
whole leg US vs
Proximal leg
veins only plus
D-dimer testing,
decide if
methods are
comparable for
management of
symptomatic
outpatients with
suspected DVT
No significant
obvious
weaknesses,
Excluded certain
groups from the
study, pregnant,
previous VTE,
suspected PE.
No difference in
outcome reported,
similar findings in
both trial groups.
Both methods are
safe
Applied method of
investigation is
dependent on
resources available,
RCT is needed to
decide whether the
quest for finding
distal DVT is
leading to
unnecessary and
potentially harmful
treatment for some
patients
Mainly
descriptive in
style.
The largest trial of the
reviewed research.
Found the initial
difference between the
numbers of DVT found in
each group could be
accounted for by CDVT.
It is likely that without calf
vein scan these DVT
would not have been
found and not treated,
what can’t be determined
is how many actual DVT
there were in the
proximal only scan group
that may have had a
distal CDVT and
therefore the significance
of that CDVT.

27. 25
Appendix C.
A general overview of significance by author.
Author Should
CDVT be
identified?
Is CDVT significant enough to
treat?
Kret et al. Yes Yes
Pengas et al. Yes Observe and treat if propagation
occurs.
Singh et al. Yes Yes, in high risk groups. Observe
in asymptomatic patients.
De-Martino et al. Yes Yes
Masuda et al. Yes Observation and treatment are
equally effective. High risk
patients may need
anticoagulation.
Schwarz et al. Yes Depends on the patient risk
group.
Johnson et al. Yes No comment made.
Sales et al. Yes Not routinely, risk dependent.
Palareti et al. Uncertain Not routinely.
Lautz et al. Yes Yes
Sule et al. Yes Observe, treat if propagation
occurs.
Parisi et al. Yes Observation and selective
treatment in higher risk groups.
Sevestre et al. Yes Identified CDVT was treated in
this study.
Gibson et al. Uncertain Uncertain
Bernardi et al. Uncertain Uncertain