Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study

Papers
Compression ultrasonography for diagnostic management
of patients with clinically suspected deep vein thrombosis:
prospective cohort study
Alberto Cogo, Anthonie W A Lensing, Maria M W Koopman, Franco Piovella, Sergio Siragusa,
Philip S Wells, Sabina Villalta, Harry R Büller, Alexander G G Turpie, Paolo Prandoni
Abstract
non-invasive tests. Impedance plethysmography was
See editorial by
the first well evaluated non-invasive method and had a
Davidson and
Objective: To evaluate the safety of withholding
Deppert
high accuracy for proximal vein thrombosis in sympto-
anticoagulant treatment from patients with clinically
matic patients but was less sensitive for thrombi
Istituto di
suspected deep vein thrombosis but normal findings
Semeiotica Medica,
confined to the calf veins.3 Therefore, impedance
University of Padua,
on compression ultrasonography.
plethysmographic tests needed to be repeated several
35128 Padua, Italy
Design: Compression ultrasonography was done with
times to detect proximally extending thrombi in the
Alberto Cogo,
a simplified diagnostic procedure limited to the
research fellow
calf vein. In early studies, impedance plethysmography
common femoral vein in the groin and the popliteal
Sabina Villalta,
was repeated five times over 2 weeks in patients who
research fellow
vein extending down to the trifurcation of the calf
Paolo Prandoni,
veins. Patients with normal ultrasonography findings
had an initially normal test result.4 5 In subsequent
senior researcher
at presentation were retested 1 week later.
studies, the efficiency of the test procedure was further
Policlinico San
Main outcome measure: The incidence of venous
improved by reducing the number of repeat tests to
Matteo, Clinica
thromboembolic complications during follow up for 6
three and later to two tests without compromising
Medica Seconda,
27100 Pavia, Italy
months in patients in whom anticoagulant treatment
safety.6–8
Franco Piovella,
was withheld on the basis of normal results on two
Over the past decade, compression ultrasonogra-
senior researcher
ultrasonography tests 1 week apart.
phy has emerged as the non-invasive method of choice
Sergio Siragusa,
Setting: University research centres in four hospitals.
for the evaluation of patients with clinically suspected
research fellow
Results: A total of 1702 patients were included in the
deep vein thrombosis because of its excellent accuracy
HGH McMaster
study. Abnormal results on compression
for deep vein thrombosis and wide availability.8–10 The
Clinic, Hamilton
General Hospital,
ultrasonography at presentation or at 1 week were
procedure can be limited to a single spot in the groin
Hamilton, Ontario
found in 400 and 12 patients, respectively, for a
and mid-popliteal fossa, where clear and reproducible
L8L 2X2, Canada
prevalence of deep vein thrombosis of 24%. None of
images can be obtained.8–11 As is the case for
Philip S Wells,
research fellow
the patients were lost to follow up. Venous
impedance plethysmography, however, compression
Alexander G G
thromboembolic complications during the week of
ultrasonography cannot accurately evaluate the calf
Turpie,
serial testing occurred in a single patient and in eight
veins.9 Consequently, serial compression ultrasonogra-
senior researcher
patients during 6 months’ follow up, resulting in a
phy testing remains necessary. To identify the relatively
Centre for Vascular
cumulative rate of venous thromboembolic
few patients whose compression ultrasonography
Medicine, Academic
Medical Centre,
complications of 0.7% (95% confidence interval 0.3%
result will convert from normal to abnormal, however,
H-2, 1105 AZ
to 1.2%). The mean number of extra hospital visits
the test has to be repeated twice in all patients with an
Amsterdam,
and additional tests required per initially referred
initial normal test result.8 12 This diagnostic approach is
Netherlands
Anthonie W A
patient was 0.8.
inconvenient for patients, labour intensive, and
Lensing,
Conclusion: It is safe to withhold anticoagulant
expensive. Recent observations showed that some
senior researcher
treatment from patients with clinically suspected deep
symptomatic patients with normal results on compres-
Maria M W
vein thrombosis who have a normal result on
sion ultrasonography in the mid-popliteal fossa have
Koopman,
senior researcher
compression ultrasonography at the time of
thrombi confined to the more distal part of the
Harry R Büller,
presentation and at 1 week.
popliteal vein.11 12 This could imply that an evaluation
senior researcher
of the popliteal vein extending down to the trifurcation
Correspondence to:
Introduction
of the calf veins has the potential to increase sensitivity
Dr Lensing
of the test at presentation necessitating only one repeat
a.w.lensing@amc.
uva.nl
Contrast venography is the standard method for the
ultrasonography test 1 week later.
diagnosis of deep vein thrombosis, but its widespread
We evaluated the simplified ultrasound strategy in a
BMJ 1998;316:17–20
use is hampered mainly due to the invasive nature of
large series of consecutive patients with clinically
the test, limited availability, and the side effects
suspected deep vein thrombosis. The clinical validity of
associated with the use of contrast material.1 2 These
withholding anticoagulant treatment from patients
limitations formed the basis for the development of
who had normal results on compression ultrasonogra-
BMJ VOLUME 316 3 JANUARY 1998
17

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Papers
phy on presentation and on a single repeat test 1 week
was scanned with the patient in the prone or lateral
later was assessed during follow up for 6 months.
decubitus position and the transducer placed
posteriorly in the mid-popliteal fossa. Assessment of
Patients and methods
the proximal veins along their entire course in the
thigh results in loss of specificity and is not indicated
Patients
because symptomatic patients with venous thrombosis
All patients referred to one of the participating centres
usually have large thrombi affecting at least the
with a suspected first episode of deep vein thrombosis
popliteal or common femoral vein.11 For the evaluation
of the leg were potentially eligible for the study.
of the distal popliteal vein, the transducer was moved
Patients were excluded if they had had deep vein
slowly from the popliteal fossa along the calf down to
thrombosis in the past, had received anticoagulant
the trifurcation of the calf veins. No attempt was made
treatment for more than 48 hours, had a contraindica-
to evaluate the calf veins. Failure to compress the
tion to contrast venography, were under 18 years old,
lumen of the vein fully during compression with the
or lived too far from the study centre to return for fol-
ultrasound transducer was the sole criterion for the
low up visits. In addition, patients who presented with
presence of deep vein thrombosis.9 Proximal deep vein
concurrent symptoms of pulmonary embolism were
thrombosis was excluded if both the common femoral
excluded as symptomatic pulmonary embolism consti-
and popliteal vein were fully compressible and no
tuted one of the main study outcomes. Eligible patients
residual lumen was seen. Ultrasonic findings were
who gave informed consent were enrolled. The study
scored as normal, abnormal, or inadequate for
protocol was approved by the institutional review
interpretation.
boards.
Analysis
Study design
The outcome measure was the total rate of
The objective of this study was to determine the clinical
symptomatic venous thromboembolic complications
validity of normal compression ultrasound tests with a
during follow up over 6 months defined as either a
simplified examination limited to the common femoral
pulmonary embolism occurring before repeat ultra-
vein and the popliteal vein extending down to the
sonography or as pulmonary embolism or a deep vein
trifurcation of the calf veins. Patients with a normal
thrombosis during long term follow up. The total com-
result at presentation were not treated with anticoagu-
plication rate was calculated with Kaplan-Meier
lants and were scheduled for a single repeat test 1 week
survival analysis and was defined as 1 minus the com-
later which was performed with an identical approach
plication free survival rate. This method takes into
as at presentation. If the repeat test also yielded normal
account the different numbers of patients at risk
results patients were considered not to have deep vein
during the different time periods. An estimate of the
thrombosis and anticoagulant treatment was withheld.
exact 95% confidence interval was made with the SD as
These patients were followed up for a period of 6
calculated by the Kaplan-Meier analysis.
months and were asked to return to the study centre at
It was estimated that about 1650 patients were
3 and 6 months or immediately if they had signs or
needed to conclude with sufficient confidence that the
symptoms of pulmonary embolism or deep vein
clinical validity of our simplified compression ultra-
thrombosis.
sound strategy was at least equivalent to that of the ear-
During follow up visits patients were questioned
lier non-invasive diagnostic strategies which used more
about their general health, recent hospital admissions,
repeat tests to exclude deep vein thrombosis. Feasibility
possible complications of venous thromboembolism,
was expressed as the mean number of extra visits to the
and use of anticoagulant treatment. Patients who did
hospital and the mean number of additional tests
not return for follow up assessments were interviewed
required per initially referred patient.
by telephone. Confirmatory testing (that is, contrast
venography, perfusion-ventilation lung scanning, or
pulmonary angiography) was planned in all patients
Results
with suspected venous thromboembolic complica-
During the recruitment period, 2113 consecutive
tions.8 Necropsies were requested for all patients who
outpatients with clinically suspected deep vein
died and in whom pulmonary embolism could not be
thrombosis were referred to the study centres for
excluded as the cause of death. An independent physi-
objective testing. Three hundred and seventy two
cian determined the cause of death if necropsy could
patients (17.6%) were excluded from the study: 175
not be performed. Most patients with abnormal
with previous venous thrombosis, 77 had already
ultrasonography findings had confirmatory venogra-
started long term anticoagulant treatment, 52 because
phy to assess the positive predictive value.
of geographic inaccessibility, 24 had contraindications
to contrast material, 20 with clinically suspected
Ultrasonography technique
pulmonary embolism at the time of referral, 15 were
The ultrasound examinations were performed with a
pregnant, five were aged less than 18 years, and in four
7.5-MHz linear array sonographic scanner (Advanced
ultrasonography could not be performed because of
Technology Laboratories, ATL Ultramark 4, Bothell,
plaster cast or leg amputation. Thus, a total of 1741
Washington, United States). Only the common femoral
patients were ruled eligible for the study, of whom 38
and popliteal veins were evaluated.9 10 With the patient
refused to give informed consent. Therefore, our
in the supine position, the common femoral vein was
analysis included 1703 patients, of whom 1046 (61%)
visualised at the inguinal ligament by using the
were women. The mean (range) age of the study
adjacent artery as a reference point. The popliteal vein
subjects was 63.9 (18 to 96) years, and the median
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Papers
Summary of non-invasive diagnostic strategies used in patients with clinically suspected deep vein thrombosis
Mean No of extra hospital
Prevalence of deep vein
Complications during 3 month visits/additional tests required per
Reference
Diagnostic strategy
thrombosis (%)
follow up (95% CI)
patient
Impedance plethysmography
Hull 19854
At days 1, 2, 3, 5 or 7, 10, 14
21
1.7 (0.2 to 3.1)
4.1
Hull 19854
At days 1, 2, 3, 5 or 7, 10, 14*
29
1.8 (0.2 to 3.4)
3.9
Huisman 19866
At days 1, 2, 5, 10
30
0.7 (0 to 1.6)
2.1
Huisman 19897
At days 1, 2, 7
45
0.8 (0 to 2.2)
1.3
Prandoni 199115
At days 1, 3, 7
18
2.6 (0.8 to 4.3)
1.7
Heijboer 19938
At day 1, 2, 8
24
2.4 (0.9 to 4.0)
1.6
Compression ultrasonography
Sluzewski 199112
At days 1, 2, 7
27
1.3 (0 to 3.9)
1.3
Heijboer 19938
At days 1, 2, 8
21
1.5 (0.3 to 2.8)
1.6
Current study
At days 1, 7
24
0.7 (0.3 to 1.2)
0.8
*Combined with iodine-125 fibrinogen leg scanning.
(range) interval between the onset of symptoms and
liver cirrhosis (one). In 16 patients with normal results
the day of referral was 6 (1 to 60) days.
on ultrasonography at presentation the protocol was
violated: anticoagulant treatment was initiated in seven
Ultrasonography
patients and venography was performed in nine
Adequate compression ultrasonography results were
patients. Isolated calf vein thrombosis was found in one
obtained for 1702 of the 1703 consecutive patients. Of
of these patients.
the 412 (24%) patients with abnormal results, 400 were
detected at presentation and 12 on repeat testing.
Repeat testing was refused by 33 patients because signs
Discussion
and symptoms of deep vein thrombosis had disap-
Serial non-invasive testing for the diagnosis of sympto-
peared. A total of 26 patients (23 at presentation and
matic deep vein thrombosis is necessary because a
three on repeat testing 1 week later) had normal results
proportion of patients with less extensive disease will
for the common femoral vein and at the level of the
have initial normal test results which may convert to
mid-popliteal fossa but thrombosis was identified in
abnormal on subsequent days.4–8 In the initial studies, a
the distal popliteal vein.
total of five tests were performed. Currently, three tests
(at referral, the next day, and 1 week later) are required
Follow up
for optimal management.
Three patients presented before the scheduled repeat
The results of this study in a large series of patients
test at 1 week with clinically suspected pulmonary
with clinically suspected deep vein thrombosis indicate
embolism; this was not confirmed by objective testing
that compression ultrasound with a simplified examin-
in two patients. The remaining patient, who initially
ation is able both to identify most patients with deep
presented with leg pain after calf muscle trauma, devel-
vein thrombosis and to reduce safely the number of
oped sudden shortness of breath on the fifth day after
repeat tests to a single one with an interval of 1 week.
the initial normal result. The patient was admitted to a
Patients with an initial normal test result were not
local hospital and received low dose subcutaneous
treated with anticoagulants and were scheduled for
standard heparin (5000 IU twice daily). No diagnostic
repeat testing 1 week later. Six months of follow up in
investigations were performed. The next day the
patients with normal results showed a cumulative rate
patient died, and necropsy revealed a massive
of venous thromboembolic complications of only
pulmonary embolism. Eighteen patients returned
0.7%; a finding which is at least equivalent to results
before the scheduled 3 month follow up visits because
observed in earlier studies that used serial impedance
of recurrent or aggravating symptoms of deep vein
plethysmography or compression ultrasonography
thrombosis of the leg (17 patients) or clinically
(table 1).6–8 12
suspected pulmonary embolism (one patient). Com-
In recent studies evaluating serial compression
pression ultrasonography and venography confirmed
ultrasonography, two additional tests were needed to
the presence of deep vein thrombosis in seven patients
identify about 7% of the total number of patients with
and excluded deep vein thrombosis in 10. Perfusion-
deep vein thrombosis.8 12 With use of the simplified
ventilation lung scanning confirmed the presence of
ultrasound examination only 3% of the total number
pulmonary embolism in the other patient. No
of patients with deep vein thrombosis were identified
suspected venous thromboembolic complications
by the single repeat test without observing an
occurred after the 3 month follow up visit. The overall
increased risk for venous thromboembolic complica-
cumulative incidence of venous thromboembolic com-
tions at follow up. The extended evaluation of the pop-
plications (that is, pulmonary embolism before repeat
liteal vein down to the trifurcation of the calf veins
ultrasonography at 1 week and pulmonary embolism
resulted in the identification of small proximal deep
or deep vein thrombosis during long term follow up)
vein thrombosis in an additional 26 patients, 6.3% of
was therefore 0.7% (95% confidence interval 0.3% to
the total number of patients with confirmed venous
1.2%).
thrombosis. The mean number of extra hospital visits
Twenty one patients died during the follow up over
and additional tests required per initially referred
6 months: cancer (11 patients), myocardial infarction
patients was 0.8, which is considerably lower than that
(four), stroke (three), congestive heart failure (two), and
found in previous studies evaluating non-invasive diag-
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Papers
We thank Drs L Vicentini, S Carbone, C Beltrametti, M Barone,
Key messages
and J Johnson for their technical help throughout the study.
Contributors: AWAL and PP designed the protocol, initiated
+ Clinical diagnosis of suspected deep vein
and coordinated the study, analysed and interpreted the data,
thrombosis is notoriously unreliable and
and are responsible for writing the paper. AC, FP, HRB, and
objective diagnostic tests are indicated to
AGGT were the local principal investigators who discussed core
ideas and participated in the protocol design and execution of
confirm or refute the presence of this condition
the study, particularly data documentation and quality control.
+ Ultrasonography with vein compressibility of
They also edited the manuscript. MMWK, SS, PSW, and SV par-
the common femoral and popliteal vein is the
ticipated in the execution of the trial, particularly in assessing
non-invasive test of choice for the diagnostic
the patients for inclusion, performing ultrasound tests, and
monitoring patients during follow up.
management of patients with suspected deep
Funding: AWAL received a grant from the Dutch foundation
vein thrombosis
De Drie Lichten.
+ It is safe to withhold anticoagulant treatment
Conflict of interest: None.
from patients with suspected deep vein
thrombosis who have normal results on
1 Lensing AWA, Hirsh J, Büller HR. Diagnosis of venous thrombosis. In:
compression ultrasonography on presentation
Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and throm-
and on a single repeat test 1 week later
bosis: basic principles and clinical practice. 3rd ed. Philadelphia: Lippincott,
1993:1297-321.
+ With the simplified compression ultrasound
2 Lensing AWA, Prandoni P, Büller HR, Casara D, Cogo A, Cate JW. Lower
extremity venography with iohexol: results and complications. Radiology
strategy the number of repeat tests can be safely
1990;77:503-5.
reduced to a single test performed a week after
3 Hull RD, van Aken WG, Hirsh J, Gallus AS, Hoicka G, Turpie AG, et al.
presentation
Impedance plethysmography using the occlusive cuff technique in the
diagnosis of venous thrombosis. Circulation 1976;53:696-700.
+ Most patients with deep vein thrombosis can be
4 Hull RD, Hirsh J, Carter CJ, Jay RM, Ockelford PA, Buller HR, et al. Diag-
identified at presentation, making this strategy
nostic efficacy of impedance plethysmography for clinically suspected
deep-vein thrombosis: a randomized trial. Ann Intern Med 1985;102:21-6.
convenient to patients and less costly
5 Hull RD, Raskob GE, Carter CJ. Serial impedance plethysmography in
pregnant patients with clinically suspected deep-vein thrombosis. Clinical
validity of a negative finding. Ann Intern Med 1990;112:663-7.
6 Huisman MV, Büller HR, ten Cate JW, Vreeken J. Serial impedance
nostic strategies for suspected deep vein thrombosis
plethysmography for suspected deep venous thrombosis in outpatients.
The Amsterdam general practitioner study. N Engl J Med 1986;314:823-6.
(table 1).
7 Huisman MV, Büller HR, ten Cate JW, Heijermans HSF, van der Lan J,
Although the use of the extended popliteal vein
van Maan en DJ. Management of clinically suspected acute venous
examination allowed for the earlier identification of
thrombosis in outpatients with serial impedance plethysmography in a
community hospital setting. Arch Int Med 1989;149:511-5.
patients with proximal vein thrombosis, the procedure
8 Heijboer H, Büller HR, Lensing AWA, Turpie AGG, Colly LP, ten Cate JW.
resulted in more false positive test results. Thus, the
A comparison of real-time ultrasonography with impedance plethys-
mography for the diagnosis of deep-vein thrombosis in symptomatic
positive predictive value for the assessment of the com-
outpatients. N Engl J Med 1993;329:1365-9.
mon femoral vein and the popliteal vein in the
9 Lensing AWA, Prandoni P, Brandjes D, Huisman PM, Vigo M, Tomasella
mid-popliteal fossa was 98.5%, whereas this was 79%
G, et al. Detection of deep-vein thrombosis by real-time B-mode
ultrasonography. N Engl J Med 1989;320:342-5.
for the distal popliteal vein examination.
10 Appelman PT, de Jong TE, Lampmann LE. Deep venous thrombosis of
The reduction of the number of repeat ultrasound
the leg: US findings. Radiology 1987;163:743-8.
11 Cogo A, Lensing AWA, Prandoni P, Hirsh J. Distribution of thrombosis in
assessments to a single test 1 week later is clearly asso-
patients with symptomatic deep vein thrombosis: implication for simpli-
ciated with lower costs but remains relatively cost inef-
fying the diagnostic process with compression ultrasound. Arch Intern
fective as most patients with an initial normal result on
Med 1993;153:2777-80.
12 Sluzewski M, Koopman MMW, Schuur KH, van Vroonhoven TJMV, Ruijs
ultrasonography do not have venous thrombosis.
JHJ. Influence of negative ultrasound findings on the management of in-
Although only 3% (upper 95% confidence limit 5%) of
and outpatients with suspected deep-vein thrombosis. Eur J Radiol
1991;13:174-7.
patients with venous thrombosis were identified by the
13 Wells PS, Brill-Edwards P, Stevens P, Panju A, Patel A, Douketis J, et al. A
repeat test 1 week later, one can speculate whether this
novel and rapid whole blood assay for D-dimer in patients with clinically
repeat test is actually needed. We consider that such an
suspected deep vein thrombosis. Circulation 1995;91:2184-7.
14 Wells PS, Hirsh J, Anderson DR, Lensing AWA, Foster G, Kearon C, et al.
attractive option from the point of view of hospital
Accuracy of clinical assessment of deep-vein thrombosis. Lancet
logistics is still offset by the potential for fatal
1995;345:1326-30.
pulmonary embolism. Further refinements of the diag-
15 Prandoni P, Lensing AWA, Buller HR, Vigo M, Cogo A, ten Cate JW. Fail-
ure of computerized impedance plethysmography in the diagnostic
nostic strategy with the high negative predictive value
management of patients with clinically suspected deep-vein thrombosis.
of the D-dimer assay13 and the use of clinical decision
Thromb Haemost 1991;65:233-6.
rules,14 however, show promise.
(Accepted 6 August 1997)
Fifty years ago
The new NHS:Consultants and the Act
See editorial by Macpherson
Such is the confusion of minds and of tongues in the
consultants and specialists may accept this as an
consultant and hospital world that there is unlikely to
inevitable step, and some may accept it as a desirable
be any effective challenge to the proposed transfer on
step, we believe that the majority are still opposed to a
July 5, 1948, of the hospitals of Great Britain into the
State Medical Service. In the last plebiscite more than
ownership of the State. The implications of this
50% of consultants and specialists voting voted against
revolutionary step will become more and more visible
negotiations with the Minister under the present Act.
as the months and the years pass. While many
(BMJ 1948;i:17)
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