Ultrasonography and Diagnosis of Venous Thromboembolism

Brenda K. Zierler

Circulation. 2004;109:I-9-I-14
doi: 10.1161/01.CIR.0000122870.22669.4a
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 Ultrasonography and Diagnosis of
Venous Thromboembolism
Brenda K. Zierler, PhD

Abstract—Venous thromboembolism (VTE) consists of two related conditions: pulmonary embolism (PE) and deep vein
thrombosis (DVT). Objective testing for VTE is crucial because the clinical diagnosis is nonspecific and insensitive, and
the consequences of a missed diagnosis are serious. The purpose of this review is to discuss the utility of venous
ultrasonography as the foundation for diagnosis of acute lower extremity DVT. The effectiveness and practicality of
venous ultrasonography as a stand-alone examination versus theoretically attractive, but perhaps less practical,
combined approaches of ultrasonography with clinical probability assessment and D-dimer testing in the diagnosis of
acute DVT is also addressed. Finally, the role of venous ultrasonography in a diagnostic algorithm for suspected PE is
discussed. (Circulation. 2004;109[suppl I]:I-9-I-14.)
Key Words: thrombosis 䡲 pulmonary heart disease 䡲 diagnosis 䡲 ultrasonics 䡲 veins 䡲 prevention

Current Treatment Standards for DVT
Guidelines for antithrombotic therapy for the treatment of
venous thromboembolism (VTE), developed in 2001 by the
Sixth American College of Chest Physicians (ACCP), state
that patients with acute VTE should be treated with low
molecular weight heparin, unfractionated intravenous hepa-
rin, or adjusted-dose subcutaneous heparin.1 Treatment is
recommended for both proximal and symptomatic distal
(isolated calf) DVT. If anticoagulation cannot be adminis-
tered or is contraindicated for calf DVT, then the recommen-
dations are for serial noninvasive studies over the next 10 to
14 days to assess for proximal progression of the thrombus.1
These recommendations, in effect, require that an examina-
tion assessing the presence of DVT have both excellent
sensitivity and specificity for diagnosis of both proximal
(above knee) and distal (below knee) DVT. Currently, color
flow duplex scanning performed by skilled operators pro-
vides the most practical and cost-effective method for assess-
ing DVT of the proximal and distal lower extremity veins.
Unfortunately, most duplex ultrasound-based algorithms
for the diagnosis of DVT, and some vascular laboratories,
still do not include an initial ultrasound evaluation of the calf
veins as part of their routine evaluation for DVT, even in
symptomatic patients. This is largely the result of outdated
perceptions of the inaccuracy of ultrasound evaluation of
DVT isolated to the calf veins. Failure to perform a complete
initial examination necessitates serial ultrasound examina-
tions or alternative strategies to detect possible extension of
venous thrombi initially isolated to the calf veins. Such
strategies are inefficient, and unlikely to be cost effective,
compared with the modern practice of a single stand-alone
color flow duplex study of the proximal and distal lower
extremity veins in patients with suspected DVT.
Limitations of Current Noninvasive Diagnostic
Methods for DVT
Impedance Plethysmography
The objective diagnosis of DVT is not always straightfor-
ward. Venography was once accepted as the standard of
accuracy for diagnosing DVT2 and still has some limited
indications. However, because of its invasive nature, techni-
cal difficulty, and cost, venography is not suitable for routine
clinical evaluation of possible DVT. Before the acceptance
and widespread use of venous duplex scanning, impedance
plethysmography (IPG) was employed as the initial noninva-
sive test for patients with suspected acute lower extremity
DVT.3– 6 According to studies that compare IPG to venogra-
phy and exclude clinical outcome, its sensitivity for proximal
DVT ranges around 65%.7– 8 IPG may not detect nonocclu-
sive proximal DVT or occlusive proximal DVT present in
parallel venous systems, such as duplicated femoral or
popliteal veins, and cannot detect DVT isolated to the calf
veins.9
Venous Ultrasonography
Venous ultrasonography has become the most widely used
diagnostic modality, invasive or noninvasive, for the diagno-
sis and exclusion of acute DVT. Duplex ultrasound is
considered to be the primary noninvasive diagnostic method
for DVT. It is required as primary instrumentation for
peripheral venous testing according to the standards of the
Intersocietal Commission for the Accreditation of Vascular
Laboratories (ICAVL).10 Secondary instrumentation (IPG

From the Department of Biobehavioral Nursing and Health Systems, School of Nursing, University of Washington, Seattle.
Correspondence to Brenda K. Zierler, PhD, Associate Professor, Department of Biobehavioral Nursing and Health Systems, School of Nursing,
University of Washington, Box 357266,1959 NE Pacific St, Seattle, WA 98195. E-mail brendaz@u.washington.edu
© 2004 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/01.CIR.0000122870.22669.4a

I-9
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I-10 Circulation March 30, 2004
and continuous-wave Doppler) may still be used to supple-
ment duplex ultrasonography in the diagnosis of DVT but are
not considered primary diagnostic methods for ICAVL ac-
creditation purposes.
There are several types of venous ultrasonography. They
include compression ultrasound (B-mode imaging only),
duplex ultrasound (B-mode imaging and Doppler waveform
analysis), and color Doppler imaging alone. Although these
types of venous ultrasonography are sometimes used inter-
changeably, their sensitivities and specificities for detecting
acute DVT vary.9 Different lower extremity veins are best
evaluated with different techniques. Compression ultrasound
is typically performed on the proximal deep veins, specifi-
cally the common femoral, femoral, and popliteal veins, whereas
a combination of duplex ultrasound and color Doppler imaging
is more often used to interrogate the calf and iliac veins.
Individual laboratories sometimes determine the type of
venous ultrasonography to use and the segments of the
venous system to be examined on the basis of local technol-
ogist experience and technical expertise. Unfortunately, ve-
nous ultrasonography examinations are not yet uniformly
standardized and range from compression of as few as two
deep veins to complete duplex and color Doppler evaluation
of the entire lower extremity.11–14 Limited examinations as
stand-alone studies are obviously incompatible with the
recommendations of the American College of Chest Physi-
cians. There are, however, factors that influence which
venous segments can be evaluated in an individual examina-
tion. These include presence of morbid obesity, lower ex-
tremity edema or tenderness, and the presence of immobili-
zation devices and bandages.15 Overall, however, a complete
color flow venous duplex examination has become the
standard of care for assessment of lower extremity DVT. It is
recommended that, whenever possible, a venous duplex
examination to exclude the presence of DVT consist of
evaluation of both the proximal and calf veins.
Accuracy of Venous Ultrasound
Accuracy of venous ultrasonography in comparison to venog-
raphy has been well established. The weighted mean sensi-
tivity and specificity of venous ultrasonography (including all
types) for the diagnosis of symptomatic proximal DVT are
97% and 94%, respectively. The high specificity of venous
ultrasonography allows treatment of DVT to be initiated
without further confirmatory tests, and the high sensitivity in
diagnosing proximal DVT makes it possible to withhold
treatment if the examination is negative.9 As noted above,
some ultrasound examinations are constrained by practical
matters involved in the clinical care of patients. Inability of
the patient to fully cooperate with regard to positioning for
the examination and/or intolerance of the pressure of the
ultrasound scanhead on the skin, or inability of the examiner
to obtain a complete examination secondary to the presence
of bandages, casts, or extremity wounds may, in some cases,
lead to a need for serial examinations or the performance of
an alternative diagnostic procedure such as catheter-based
contrast venography or CT (computed tomography) or MR
(magnetic resonance) venography to exclude DVT. Cur-
rently, repeat or serial venous ultrasonography seems advis-
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able for negative examinations in symptomatic patients who
are highly suspicious for DVT and in whom an alternative
form of imaging is contraindicated or not available.
Venous Ultrasonography as a Stand-Alone
Diagnostic Test
Two types of studies are performed to evaluate diagnostic
strategies for acute DVT: accuracy studies in which the new
test (venous ultrasonography) is compared with the gold
standard (venography), and management studies in which
patients are monitored over time to determine the safety of
managing patients according to the results of these tests.
Kearon et al provided a comprehensive review of accuracy
and management studies that evaluated objective tests for the
diagnosis of first and recurrent DVT in symptomatic, asymp-
tomatic, and pregnant patients.9 The authors of this review
concluded that the majority of patients with suspected DVT
could be managed with noninvasive testing; however, venog-
raphy was recommended in patients whose noninvasive test
results were nondiagnostic or discordant with the clinical
assessment (eg, negative compression ultrasound and high
clinical suspicion).
A widely recognized management trial using compression
ultrasonography as a stand-alone examination in patients
suspected of having a first episode of proximal DVT was
performed by Birdwell et al on 405 consecutive symptomatic
outpatients.11 The purpose of this study was to test the safety
of withholding anticoagulation in patients who had a normal
compression ultrasound examination of their proximal veins
at presentation and a normal follow-up test completed within
5 to 7 days later. Patients with initially abnormal ultrasound
studies were anticoagulated whereas those with normal stud-
ies underwent repeat ultrasonography. Anticoagulation was
withheld from all patients whose compression ultrasound
results remained normal regardless of their symptoms, and
these patients were monitored for 3 months. Only two
patients with initially normal studies developed DVT subse-
quently, and there were no deaths reported among patients
managed according to this algorithm. These results demon-
strate that it is safe to withhold anticoagulation in outpatients
suspected of having a first episode of DVT if compression
ultrasonography results are normal at presentation and on a
single follow-up examination done 5 to 7 days later.11
Current ultrasound technology is able to image calf veins
in the large majority of patients. A well-trained technologist
can interrogate these veins in 80% to 98% of cases using a
combination of B-mode, Doppler waveform analysis, and
color Doppler (Figures 1 and 2).16 Rose et al showed that in
technically adequate studies, the sensitivity and specificity of
color Doppler in isolated calf veins exceeded 90%.16 Others
have also shown duplex ultrasound and color Doppler sensi-
tivities for detecting isolated calf vein thrombosis to be
greater than 90%.16 –18 Extrapolating from this data, and the
fact that in the Birdwell study only two patients developed
DVT after the initial negative examination,11 it appears that
an initial negative examination that includes both proximal
and calf veins should be sufficient to withhold anticoagula-
tion and preclude the need for routine follow-up studies in
patients without clinical suspicion of pulmonary embolism.

Figure 1. Color Doppler image of normal calf veins (posterior
tibial). The paired posterior tibial veins (blue) are located on
each side of the posterior tibial artery. Duplex spectrum of pha-
sic venous flow during respiration, with increase in flow shown
by manual augmentation.
Serial duplex scans are, however, indicated for patients
who present with symptoms of possible DVT and have a
negative venous ultrasound examination that has been limited
to the proximal veins and in whom catheter-based contrast
venography is not performed. The serial scans are performed
to evaluate for propagation or extension of calf vein thrombi,
the presence of which are not readily detected by CT or MR
venography. Isolated calf vein thrombosis accounts for 20%
of symptomatic DVT, and, in some studies, approximately
Figure 2. Cross-section of posterior tibial veins and artery. One
of the posterior tibial veins has thrombus and is demonstrated
on the B-mode image. The vein was incompressible. The other
posterior tibial vein is patent demonstrated by Doppler flow and
color Doppler imaging (blue).
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Zierler Diagosing VTE I-11
one quarter of untreated symptomatic calf vein thrombi will
extend proximally within 1 to 2 weeks.19
The Problem of the Negative Study
It is currently estimated that 1 million patients per year
undergo ultrasound examination for suspected DVT. Of these
examinations, only 12% to 25% are positive.9 Because of the
cost associated with negative examinations and, in many
locations, the burden that after-hours examinations place on
retention of vascular technologists, a number of strategies
have been developed to decrease the number of negative
examinations. The most common alternatives that have been
investigated as an alternative to immediate duplex evaluation
of anyone suspected of DVT are clinical prediction models20
and the measurement of D-dimer levels.21
Combined Approaches in the Diagnosis
of DVT
Recently, algorithmic approaches using a combination of
clinical assessment, D-dimer measurements, and ultrasonog-
raphy have been adopted into clinical practice with the goals
of standardizing the diagnostic approach to DVT and reduc-
ing the number of negative ultrasound examinations.22–27 The
utility of algorithms in the diagnosis of DVT, however,
depends on the availability of diagnostic testing, the expertise
of the technologists performing the ultrasound examinations,
the patient population, the cost and reimbursement of the
different tests, and the interpretation of the results. What
might be feasible for one institution may not be applicable to
another, and each group should determine their own approach
with some objective validation. For example, a strategy for
diagnosing DVT that utilizes venography is useless for
institutions where venography is no longer available. There-
fore, potential approaches to limiting the use of ultrasound
examinations in the evaluation of possible DVT will likely be
organization-specific. Although algorithms offer multiple
strategies for improving the diagnostic process for DVT, level
1 evidence on the validity and safety of these algorithms is
lacking. There have been no large, randomized, multicenter
studies comparing the outcomes of branching pathways that
included adequate sample sizes, which are needed to test the
safety of these algorithms. However, there have been some
rigorously performed cohort studies that have incorporated
algorithms utilizing clinical pretest probability in combina-
tion with ultrasonography and/or D-dimer testing.22–27
Clinical Assessment in Combination With
Venous Ultrasonography
Symptoms and signs are obviously inadequate alone for
evaluation of possible DVT. However, some clinical presen-
tations are more likely than others to be associated with DVT.
Wells et al developed a model to assess the clinical likelihood
of DVT in outpatients who present with suspected DVT.20
Based on the presence of thrombotic risk factors, clinical
signs, and symptoms, as well as the possibility of alternative
diagnoses, patients are stratified into 3 risk categories—low,
moderate, and high (Table 1). Patients who present with at
least one DVT risk factor and the classical symptoms of
unilateral pain and swelling have an 85% probability of
I-12 Circulation March 30, 2004
Clinical Model for Predicting Pretest Probability for
Acute DVT20,22
Clinical Features/Risk Factors Score
Active cancer within 6 months (ongoing treatment or palliative)
Immobilization by paralysis or plaster dressings
Recent surgery (within 4 weeks) or bed rest longer than 3 days
Localized tenderness along distribution of the deep venous
system
Calf swelling (⬎3-cm increase in calf circumference compared
to asymptomatic leg) measured 10 cm below tibial tuberosity
Thigh and calf swelling (entire swollen leg)
Pitting edema confined to symptomatic leg
Collateral superficial veins (nonvaricosed)
Alternative diagnosis as likely or greater than that of DVT ⫺2
Pretest probability calculated as the total score: low ⱕ0; moderate 1 or 2;
high ⱖ3. In the newer scoring system proposed by Wells et al the probability
of having a DVT is likely if a score of two or higher is obtained; a score of less
than two indicates that the probability of acute DVT is unlikely.27 The more
symptomatic leg is used if patients have symptoms in both legs.
having DVT. Outpatients who present with no identifiable
risk factors and with features not typically associated with
DVT have about a 5% probability of actually having DVT.20
Wells et al performed an evaluation of pretest probability
assessment before compression ultrasound in 593 patients
with possible DVT.22 Patients with low pretest probability
underwent a single ultrasound test of the proximal veins. A
negative ultrasound was considered to exclude acute DVT. A
positive ultrasound was confirmed by venography. More than
half the patients had 0 or fewer points and were classified as
having a “low” pretest probability of DVT. One third had 1 or
2 points and were of “moderate” pretest probability, whereas
14% had at least 3 or more points and were assessed at “high”
pretest probability. The incidence of positive venous ultra-
sound studies in these three groups (low, moderate, and high)
was 3%, 17%, and 75%, respectively.22 The study did not
address the issue of possible extension of calf vein thrombi
over time.
D-Dimer Testing
The evaluation of a pretest probability model in conjunction
with D-dimer testing has also been performed as a means to
decrease the number of serial ultrasound examinations and to
reduce the number of false-negative or false-positive ultra-
sound studies in patients suspected of acute DVT.22–28 The
use of D-dimer is controversial and, more importantly, the
precise role of D-dimer assays as an adjunct to ultrasound
examination for DVT has not been definitively established.15
D-dimer measurements have a lower sensitivity for isolated
calf vein thrombi, and the negative predictive value of
D-dimer varies with the pretest probability of disease. Al-
though the negative predictive value is exceptionally good in
low-risk patients, it is unacceptable in high-risk patients.
D-dimer assays are continuing to be explored as part of the
diagnostic work-up of VTE, but at this time, these assays
have not been standardized and the results are variable and
depend on thrombus location, size, interpretation of the
results, and other factors. Results from one study utilizing
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D-dimer assays cannot be extrapolated to results obtained by
others because the various assays for D-dimer differ in their
sensitivity and specificity.
Several studies have shown the utility of D-dimer in
1
combination with clinical assessment in the initial investiga-
1 tion of outpatients with suspected DVT.21,24,26,27 In the most
1 recent study by Wells et al,27 1096 consecutive outpatients
1 suspected of DVT were scored according to the clinical
likelihood of having a DVT and were then randomized to
1 undergo ultrasound imaging alone or to undergo D-dimer
testing and then ultrasound imaging (unless the D-dimer test
1 was negative and the patient was considered unlikely to have
1 a DVT). Only 0.4% of patients in whom DVT was ruled out
1 by D-dimer testing developed DVT. The authors concluded
that DVT could be ruled out in a patient who was scored to
be clinically unlikely to have a DVT and who had a negative
D-dimer test (using two different D-dimer assays with high
negative predictive value for DVT). They also concluded that
ultrasound could be safely omitted in patients with a negative
D-dimer and a low clinical likelihood of DVT. Although the
results of this randomized trial are promising, it is important
to note that the study population consisted of outpatients and
further validation studies for high-risk inpatients with multi-
ple comorbidities need to be performed.
The Problem of Acceptance of Limiting
Venous Duplex Scans
Clinical models for standardizing the assessment of patients
presenting with suspected DVT have been used in research
settings and in some dedicated thrombosis centers in Canada
and Europe. They are, however, not well accepted and
infrequently used in routine clinical practice. Reasons for this
include the complexity of the algorithms for routine clinical
practice, medical-legal considerations, and the practical fact
that a negative venous duplex ultrasound examination of the
proximal and distal veins allows the evaluating physician to
immediately consider alternative diagnoses.
Although the clinical diagnosis of VTE may be improved
with the use of the Wells’ clinical probability model and
D-dimer measurements, there is considerable disagreement
about the order in which these strategies should be used to
exclude the diagnosis of DVT and PE, and to reduce the
number of serial ultrasound studies.23,26,28 There are several
reviews that outline various approaches to the diagnosis of
acute VTE.9,12,13,15,23–27,29 –33 The reader is advised to consider
one that most closely matches their practice and their patient
population. It is likely that algorithms, particularly those
incorporating D-dimer testing, will become more widely
utilized in ongoing attempts to limit costs and improve the
efficiency of diagnostic processes for patients. One such
potential algorithm is outlined in Figure 3.
The Role of Venous Ultrasonography in the
Diagnosis of PE
As for acute DVT, the diagnosis of PE cannot be established
without objective testing. There have been several studies
evaluating the utility of duplex ultrasonography of lower
extremity veins in patients suspected of PE.29,30,34 –36 These
studies, often employing ultrasound of only the proximal

veins and nuclear-medicine-based ventilation perfusion
(V/Q) scanning, unfortunately, have little relevance to mod-
ern practice in which complete proximal and distal vein
ultrasound examinations are usually routine and in which CT
(CTPA) or MR pulmonary angiography (MRPA) have
largely supplanted V/Q scanning.
The rationale for employing lower extremity venous ultra-
sonography in patients who present with symptoms of PE is
that a diagnosis of DVT may indirectly suggest the diagnosis
of PE. Because anticoagulation is most often the initial
therapy for DVT and PE, it is reasoned that further investi-
gation to exclude PE may not be necessary in some clinical
settings when there is also an ultrasound diagnosis of DVT.
This approach, however, has several important limitations.
First, it does not make a definitive diagnosis of PE. Patients
can certainly have DVT and pulmonary symptoms and/or
hemodynamic instability from causes other than PE. In
addition, normal bilateral proximal venous ultrasound scans
do not rule out PE. Even when PE is definitively present,
DVT of the proximal lower extremity veins is detectable by
compression ultrasound in only 50% of patients.33 When
there is no evidence of lower extremity DVT and objective
evidence of PE, the PE may have originated from pelvic veins
or embolized completely from a lower extremity vein. Over-
all, the utility of venous ultrasonography to aid specifically in
a diagnosis of PE is limited. An objective diagnostic test for
PE is indicated in most cases. In most centers this would now
be a CT pulmonary angiogram. A diagnostic algorithm for PE
that does not include CT pulmonary angiography seems
untenable in modern practice despite the lack of level 1
evidence to support CTPA in the diagnosis of PE. The use of
MRPA is also increasing, but requires further validation in
clinical trials.31,37–39
Conclusions
Color flow venous duplex scanning of the proximal and distal
veins is the current standard for routine clinical assessment of
possible lower extremity DVT. Other invasive and noninva-
sive tests also are occasionally indicated in the assessment of
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Zierler Diagosing VTE I-13
Figure 3. Algorithm for diagnosing DVT
using clinical assessment, duplex ultrasound
of entire lower extremity, and D-dimer testing
for symptomatic patients. *Duplex ultrasound
includes complete evaluation of the lower
extremity, including compression, Doppler
waveforms, and color Doppler of the calf
veins and iliac veins. †Contrast venography
(CV) or MR venography (MRV) are warranted
if the initial duplex study is technically inade-
quate or nondiagnostic. The decision to
choose CV or MRV is dependent on the rea-
sons for the inadequate duplex. Factors
such as immobilizing devices or edema may
be temporary and serial duplex examinations
could be performed. In some centers, MRV
has proven to be sensitive and specific for
detecting thigh and pelvic DVT. If the patient
is morbidly obese, has permanent immobiliz-
ing devices, or is claustrophobic, then CV
should be performed. (The utility of MR
venography will be covered in another sec-
tion of this supplement.)
possible DVT in clinical settings where venous duplex
scanning is technically inadequate or cannot provide appro-
priate information. Diagnostic algorithms combining strate-
gies employing adjunctive tests such as clinical risk stratifi-
cation and D-dimer measurements to limit the number of
negative duplex examinations have great potential but require
that the safety of managing patients according to the algo-
rithm be proven with local validation of safety by the local
institution. Venous duplex scanning may in some cases be
useful as an adjunct to the diagnosis of PE but, in most cases,
other modern diagnostic techniques allow efficient, noninva-
sive, and direct objective diagnosis of PE in the clinical
setting.
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