Eur J Vasc Endovasc Surg (2015) -, 1e6

Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis
(DVT) Supports the Inadequacy of the Term “Proximal DVT”
a,*
M.G.R. De Maeseneer , N. Bochanen b, G. van Rooijen a, P. Neglén c

a
Department of Dermatology, Erasmus Medical Centre, Rotterdam, The Netherlands
b
Internal Medicine, University Hospital of Antwerp, Antwerp, Belgium
c
SP Vascular Center, Limassol, Cyprus

WHAT THIS PAPER ADDS

This study reports the detailed duplex ultrasound results of the largest cohort to date of patients with acute
unilateral deep venous thrombosis (DVT) of the lower extremity. It underscores the fact that the general term
“proximal DVT” should be abandoned and replaced with a more precise description of involved segments,
resulting in a further sub-classification into iliofemoral and femoropopliteal DVT with potential differentiation of
treatment.

Objective/Background: For decades acute lower limb deep venous thrombosis (DVT) has been subdivided into
distal DVT (isolated to the calf veins) and proximal DVT (extending above calf vein level). The aim of this study
was to analyse the anatomical site and extent of thrombus in a large cohort of patients with acute DVT.
Methods: A retrospective analysis of all patients aged >18 years, presenting with unilateral DVT according to
duplex ultrasound investigation was performed at the University Hospital of Antwerp, Belgium (1994e2012). The
anatomical site and extent of thrombus was registered and subdivided into five segments: calf veins (segment 1),
popliteal vein (segment 2), femoral vein (segment 3), common femoral vein (segment 4), and iliac veins, with or
without inferior vena cava (segment 5).
Results: The median age of the 1,338 patients (50% male) included was 62 years (range 18e98 years). Left sided
DVT was predominant (57%). DVT was limited to one segment in 443 patients, of whom 370 had DVT isolated to
the calf veins (28% of total cohort). In 968 patients with what was previously called “proximal DVT”, the median
number of affected segments was three (range 1e5 segments). In this group iliofemoral DVT (at least involving
segment four and/or five) was present in 506 patients (38% of total cohort), whereas the remaining patients had
femoropopliteal DVT (at least in segment two and/or three but not in four or five). Iliofemoral DVT without
thrombus in segments one and two was present in 160 patients (12% of total cohort).
Conclusion: This study illustrates the large diversity of thrombus distribution in patients previously described as
having “proximal DVT”. Therefore, this term should be abandoned and replaced with iliofemoral and
femoropopliteal DVT. Patients with iliofemoral DVT (38%) could be considered for early clot removal; 12% of all
patients with DVT would be ideal candidates for such intervention.
Ó 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Article history: Received 18 July 2015, Accepted 2 November 2015, Available online XXX
Keywords: Deep venous thrombosis (DVT), Duplex ultrasound, Iliofemoral DVT, Proximal DVT thrombus extent,
Thrombus location

thrombotic syndrome (PTS) are related to the number

INTRODUCTION
According to recent guidelines acute deep venous throm-
bosis (DVT) frequently results in significant post-thrombotic
morbidity despite adequate treatment.1,2 The risk of
developing recurrent thrombosis and the severity of post-
* Corresponding author. MGR De Maeseneer, Erasmus MC, 3015 CA
Rotterdam, The Netherlands.
E-mail address: m.demaeseneer@erasmusmc.nl (M.G.R. De Maeseneer).
1078-5884/Ó 2015 European Society for Vascular Surgery. Published by
Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejvs.2015.11.001
and anatomical site of involved venous segments.3,4 The
worst PTS occurs when the initial thrombus involves the
iliac or iliocaval outflow segment and when multiple seg-
ments are involved. Depending on the central extent of the
DVT, a different therapeutic approach may be warranted.
There is growing evidence that patients with iliocaval or
iliofemoral DVT may benefit from early clot removal by
catheter directed thrombolysis (CDT), or other means.5,6 A
meta-analysis of randomised studies comparing CDT with
anticoagulant treatment alone in patients with acute ilio-
femoral DVT has shown a reduced incidence of PTS, and less
reflux and residual obstruction.7

Please cite this article in press as: De Maeseneer MGR, et al., Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports
the Inadequacy of the Term “Proximal DVT”, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.11.001
2 M.G.R. De Maeseneer et al.

In clinical practice and in the majority of studies of acute

DVT of the lower limbs, the description of the extent and
location of thrombus has been limited to distinguishing
between “distal” and “proximal” DVT. Distal DVT is defined
as thrombus confined to one or more of the calf veins. A
proximal DVT is defined as a thrombus involving one or
more of the more central veins including the popliteal (PV),
femoral (FV), common femoral (CFV), profunda femoris,
external iliac (EIV), internal iliac, and common iliac (CIV)
veins, and the inferior vena cava (IVC). In practice, such
simple subdivision between proximal and distal is inade-
quate for two main reasons. First, considering as one large
heterogeneous group, all patients with DVT above the level
of the calf veins, causes difficulties in comparing aetiology,
pathophysiology, clinical impact, and outcome of treatment
between different studies. Second, such an imprecise
description of the extent and site of an acute DVT does not
allow for the selection of patients who might benefit from
an alternative therapeutic approach to anticoagulation
alone. The iliofemoral venous segment (iliac veins and/or
CFV, with or without IVC involvement) has to be differen-
tiated from the femoropopliteal vein segment (femoral or
popliteal venous segments or both, without extension to
the CFV or iliac veins), as it constitutes the single common
venous outflow of the lower limb and is unique in this Figure 1. Diagram used for deep venous thrombosis diagnosis
aspect. according to duplex ultrasound. The venous vasculature is
The 2012 guidelines of the Society for Vascular Surgery subdivided into five segments.
and the American Venous Forum clearly established the
need for precision in the diagnosis of DVT, with guideline of the IVC whenever feasible). In very obese patients at
1.1 stating: “We recommend use of precise terminology to least the EIV was visualised above the inguinal ligament. The
characterize the most proximal extent of venous thrombosis profunda femoris and the internal iliac veins were not
as involving the iliofemoral veins, with or without extension studied in detail. From 1994, the procedure was to draw on
into the inferior vena cava; the femoropopliteal veins; or a standardised diagram the exact location and extent of the
isolated to the calf veins in preference to simple charac- thrombus (Fig. 1). If thrombus had been found in only one
terization of a thrombus as proximal or distal”.8 of two veins of a duplicated venous system, typically at the
Only a few venographic studies have focused on the level of the FV or PV, this segment was indicated as con-
anatomy of lower extremity DVT in detail in large cohorts of taining thrombus without differentiating between thrombus
patients.9,10 Nowadays, duplex ultrasound (DUS) has in one vein or in both veins. If a concomitant superficial vein
become the gold standard for the diagnosis of DVT, but to thrombosis (SVT) was present, it was indicated on the di-
date no similar cohort study has been reported in which agram as well.
DUS had been used for DVT diagnosis. The aim of the
present study was therefore to identify precisely, and
retrospectively analyse the anatomical sites and extent of Data analysis
acute DVT in a large consecutive cohort of patients un- In 2012, a retrospective database of patients diagnosed
dergoing DUS scanning for acute DVT. with DVT at UZA was constructed. Initial diagrams of 1,701
consecutive patients presenting with a first episode of acute
DVT of the lower limb between January 1994 and July 2012
PATIENTS AND METHODS were available. Patients <18 years of age, patients with
Since 1988 all patients presenting to the Department of bilateral DVT, or files with missing data were excluded from
Thoracic and Vascular Surgery at the University Hospital of the analysis (Fig. 2). Basic demographic data such as age
Antwerp (UZA), Belgium, with clinical suspicion of DVT have and sex were directly retrieved from the patient’s identifi-
been submitted to venous colour DUS performed by well cation on the diagram. Date of DVT diagnosis, affected side
trained vascular technologists or by vascular surgeons. A (right or left), presence of a concomitant SVT, and
complete DUS of both limbs was performed, usually in the anatomical site and extent of thrombus were registered in
supine and prone position.11 This consisted of compression the database. Five segments were identified on each dia-
ultrasound, where appropriate (CFV, FV, PV), in combination gram (Fig. 1), corresponding with the following veins
with colour flow interrogation of the remaining veins (calf involved: calf veins (posterior and anterior tibial veins and
veins and veins above the inguinal ligament up to the level peroneal veins), including muscular veins (gastrocnemius
Please cite this article in press as: De Maeseneer MGR, et al., Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports
the Inadequacy of the Term “Proximal DVT”, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.11.001
Thrombus Location and Extent in DVT Patients
Figure 2. Flow diagram of the study showing selection of patients
with a first episode of acute unilateral deep venous thrombosis
(DVT) included in the analysis.
and soleus veins) (segment one); PV (segment two); FV
(segment three); CFV (segment four); and EIV/CIV with or
without IVC (segment five). Involvement of the internal iliac
vein and the profunda femoris vein was not recorded
consistently on the diagram and was excluded from the
database.
The UZA ethics committee approved the study (Ref. EC/
PC/avl/2015.016). The database was analysed for de-
mographics, side of acute DVT, location of thrombus
(affected vein segments), extent of DVT (number and pre-
sentation of affected segments), and presence of concom-
itant SVT. The left to right lower limb ratio (L:R ratio) was
calculated per segment and the global L:R ratio was calcu-
lated as the number of left sided versus right sided seg-
ments containing thrombus. An additional analysis of the
extent of thrombus was performed by examining whether
thrombus formation probably started at iliac level (e.g. in
case of an underlying compressive lesion12) and extended
peripherally (retrogradely), or started in the calf and
extended centrally (antegradely).
Statistical analysis
In order to test if the proportion of thrombus location in the
left and right leg differed from 50%, a Z-test for a single
proportion was used for each segment. The p-values were
multiplied by 5, because five segments were tested (Bon-
ferroni correction). The Z-test for two proportions was used
to test if the L:R ratio differed between segments one and
five. One-sample Z-tests were programmed using Excel 2010
(Microsoft, Redmond, WA, USA). Statistical significance was
accepted at p < .05.
RESULTS
In total, data from 1,338 patients with acute unilateral DVT
of the lower limb were available for analysis (Fig. 2). The
median age of the patients was 62 years (range 18e98
years), 50% were male, and in 57% of patients the left leg
was affected.
Please cite this article in press as: De Maeseneer MGR, et al., Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports
the Inadequacy of the Term “Proximal DVT”, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.11.001
3
Table 1. Thrombus location in segments 1e5 in left and right lower
limbs given as the total number of limbs, percentage of all lower
limbs (n ¼ 1,338) and left to right side ratio (L:R ratio).
Segment Left Right Total (%) L:R ratio
1 614 472 1,086 (81) 1.30:1
2 428 322 750 (56) 1.33:1
3 450 332 782 (58) 1.36:1
4 297 225 512 (38) 1.38:1
5 199 126 325 (24) 1.58:1
Anatomical site of the thrombus
The segments involved in the DVTs are shown in Table 1.
Thrombosis isolated to the calf veins (so called “distal DVT”)
was diagnosed in 370 patients (28%). In 325 (24%) patients
the DVT involved veins above the inguinal ligament
(segment five). There was a left sided predominance at each
of the five segments involved in DVT (Bonferroni-corrected
p < .05 for all segments). The global L:R ratio was 1.4/1 and
the L:R ratio was larger in segment five than in segment
one, but this difference did not reach statistical significance
(p ¼ .20). Concomitant SVT was present in 179 patients
(13%).
Thrombus extent
In 443 patients (33%), of whom 370 had thrombosis iso-
lated to the calf veins, DVT was limited to one segment.
DVT involved two segments in 208 patients (16%), three
segments in 345 patients (26%), four segments in 149 pa-
tients (11%), and all five segments in 193 patients (14%).
Fig. 3 shows the subdivision according to the number of
segments involved in the DVT in 968 patients with iliofe-
moral or femoropopliteal DVT. The median number of
affected segments was three (range 1e5 segments). Fig. 4
presents a more detailed analysis of the extent of
thrombus in these patients. Twenty-three patients were not
included in this sub-analysis as they had DVT in non-
adjacent segments. Of the remaining 945 patients with a
DVT previously described as “proximal”, according to the
new definition,8 iliofemoral DVT was present in 506 (54%
[38% of the total cohort]), whereas femoropopliteal DVT
was seen in the remaining 439 patients. The most
Figure 3. Number of segments involved in 968 patients with acute
unilateral “proximal deep venous thrombosis”.
4 M.G.R. De Maeseneer et al.
Figure 4. Distribution of the extent of thrombus in 945 patients
with “proximal deep venous thrombosis” in one segment, or two
and more adjacent segments. Data of 23 patients are excluded
from this analysis because they had deep venous thrombosis in
two or more non-adjacent segments.
commonly found DVT was the combination “1 þ 2 þ 3”
(femoropopliteal DVT involving the calf veins, PV, and FV) in
267 patients (20% of total cohort). Of the 506 patients with
iliofemoral DVT, 189 had no involvement of segment one,
the calf veins, and 160 (12% of the total cohort) had no
involvement of segments one or two, meaning the
thrombus did not extend more distally than the FV.
The extent of thrombus in relation to the underlying
pathophysiology
If thrombus is limited to only one segment, it must have
been initiated in that segment, unless part of the thrombus
embolised. DVT isolated to the calf veins (segment one) was
far more common (n ¼ 370) than DVT isolated to one of the
other segments: in three patients segment two alone was
involved, in 37 patients segment three, in 25 patients
segment four, and in eight patients segment five.
Thrombus probably started at the level of the calf in 872
patients (65% of total cohort): this group included those
with the extent of thrombus limited to the calf, segment 1
(n ¼ 370), thrombus located in segments 1 þ 2 (n ¼ 111),
in segments 1 þ 2 þ 3 (n ¼ 267), and in segments
1 þ 2 þ 3 þ 4 (n ¼ 124). Thrombus was most probably
formed at the iliac or iliocaval level in 126 patients (9% of
total cohort), consisting of those with thrombus in segment
5 (n ¼ 8), in segments 4 þ 5 (n ¼ 31), in segments
3 þ 4 þ 5 (n ¼ 67), and in segments 2 þ 3 þ 4 þ 5
(n ¼ 20). None of these had calf vein (segment one)
involvement. In the remaining patients with all five seg-
ments involved, it was uncertain where the thrombus was
formed initially (but most likely in the calf).
DISCUSSION
The present study reports detailed DUS findings of the
largest cohort to date of patients presenting with a first
episode of acute unilateral symptomatic DVT. It illustrates
the great diversity of thrombus location and extent in
Please cite this article in press as: De Maeseneer MGR, et al., Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports
the Inadequacy of the Term “Proximal DVT”, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.11.001
patients with acute DVT. It shows that 38% of patients with
DVT present with iliofemoral DVT. Moreover, the study
shows that in the majority of cases the thrombus was
initiated in the calf veins. It appears that approximately 9%
of all DVTs may be formed at iliac or iliocaval level and then
propagate peripherally down the lower limb.
The previous term “proximal DVT” includes a large vari-
ety of different presentations of anatomical locations and
extent of thrombi, as reported in previous venographic
studies.9,10 The present DUS study provides further insight
into the wide heterogeneity of the anatomical presentation
of “proximal DVT” (Fig. 4). Four different segments may be
distinguished at the time of diagnosis, as was registered on
the diagrams used in the present study. Equally, during
follow up, the evolution of the thrombosis (recanalisation,
collateralisation, valvular function) at each of these seg-
ments can be represented on a similar diagram for detailed
follow up, study, and audit. However, from a practical point
of view, it is sufficient to combine these four segments 2 by
2. This allows clear differentiation between thrombus in
segments two and three, described as femoropopliteal DVT,
and thrombus involving at least segment four and/or five,
described as iliofemoral DVT.8
In the present study, iliofemoral DVT was diagnosed in
506 (38%) patients. In a large cohort of 1,289 consecutive
patients with DVT, Partsch also found iliofemoral DVT in
28% of patients.13 Thus, involvement of the iliac veins and
CFV is a frequent observation. This is an important finding,
as nowadays patients with iliofemoral DVT, with or without
involvement of the IVC, may benefit from CDT, and
pharmaco-mechanical or aspiration thrombectomy, and
hence adequate patient selection at the time of diagnosis is
mandatory.5e7,14 Potentially all patients with iliofemoral
DVT are candidates for early clot removal. Of these, patients
with no calf vein thrombosis have better outcome following
invasive treatment of acute iliofemoral DVT and the ma-
jority of them (in the present study, 160 patients, 12% of
the total cohort) would have been considered “ideal” can-
didates, as there was no involvement of the PV or calf
veins.5
In the patients studied, the predominance of left sided
DVT agrees with previous findings from other large cohort
studies.3,9e13,15 The global L:R ratio (1.35) was similar to the
findings in a cohort of 885 patients with DVT examined by
venography, where a L:R ratio of 1.32 was found.9 Left sided
predominance is explained by the frequent compression of
the left CIV by the overriding right common iliac artery.12
This anatomical situation not only induces left iliac or ilio-
femoral DVT more frequently than the right, but also ap-
pears to increase the global incidence of left sided DVT,
even at the level of the calf veins (Table 1). The latter may
be explained by an enhanced venous stasis on the left side,
secondary to the compression at iliac level. The L:R ratio
was highest in segment five, the segment above the
inguinal ligament. In a large series of selected patients with
acute iliofemoral DVT, treated with catheter directed
thrombolysis, the L:R ratio was much more pronounced
(79/24, or L:R 3.29).5 Left sided predominance is also
Thrombus Location and Extent in DVT Patients
obvious in pregnancy related DVT.16,17 In a systematic re-
view of published data from patients with DVT during
pregnancy, left sided DVT was reported in 88% of women in
which the side of DVT was known.17
DVT affected a median of three segments, and in a
considerable number of patients four or even five segments
were involved. Residual thrombus burden has been shown
to influence clinical outcome after treatment.18 Patients
with DVT involving more vein segments, may have more
vein segments with incomplete recanalisation, and are
therefore more likely to develop recurrent DVT.3,4 Ipsilateral
DVT recurrence is a well known predictor of developing PTS
in the long term.2e4,15,19 Recurrent DVT is more frequent
and the PTS more severe when a post-thrombotic iliofe-
moral vein segment is present.20 A detailed description of
all the segments involved in the DVT at the time of the
acute event may allow prediction of the longer term clinical
prognosis.
Although the aetiology of DVT has been studied exten-
sively, the pathophysiology of DVT is not always clear in an
individual patient. While the three elements of Virchow’s
triad are variably expressed, one question is where the
initial thrombus is formed. In acute iliofemoral DVT there
are two main possible scenarios: either thrombus is initi-
ated in the calf and progressed centrally, or it formed at iliac
level and extended peripherally. The findings in the present
study suggest that in the majority of cases the thrombus
was formed in the calf, which is in accordance with previous
reports.9,10 However, 9% of all patients with DVT had
thrombus at the iliac or iliocaval level without thrombus in
the calf veins. This finding suggests that in these patients
thrombus initiated above the inguinal ligament, at iliac or
IVC level, and subsequently extended peripherally but did
not reach the calf. As mentioned above, in these patients it
is particularly beneficial to perform early clot removal.5 The
initial thrombus formation is probably related to central
outflow obstruction of varying types, such as an underlying
compression lesion, which may play a role in unprovoked
and provoked DVTs. A typical scenario is left sided preg-
nancy related DVT. Chan et al. found DVT involving all four
proximal segments without calf vein involvement in 71% of
women with DVT during pregnancy, and 64% of the latter
had iliofemoral DVT.16 In pregnancy related DVT a location
above the inguinal ligament is obviously far more common
than in any other patients with DVT.16 Unilateral or bilateral
iliofemoral DVT is also very common in patients with
congenital absence of the IVC or post-thrombotic obstruc-
tion of the IVC following a DVT in the neonatal period. In a
survey including 35 patients with this condition, the acute
DVT was situated at the iliac or iliofemoral level in 81% of
lower limbs.21 The pathophysiology of DVT in patients with
isolated DVT either in segments two, three, or four is
probably related to local causes. These could be an exten-
sion from an ascending SVT through the saphenofemoral
junction, through the saphenopopliteal junction, or a
perforating vein “per continuitatem” into the deep venous
system, or local trauma due to repeated access (intravenous
drug users) or other local processes. Thrombus confined to
Please cite this article in press as: De Maeseneer MGR, et al., Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports
the Inadequacy of the Term “Proximal DVT”, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.11.001
5
a single segment at the time of diagnosis can also be the
result of an initially more extensive DVT, which has resolved
owing to spontaneous fibrinolysis in adjacent segments or,
more frequently, has undergone partial embolisation into
the pulmonary circulation, resulting in subclinical or clinical
pulmonary embolism.
This study has some limitations. First, it was only possible
to analyse thrombus location and extent in general, without
distinguishing between unprovoked and provoked DVT. To
achieve this, an additional study of all patient files would
have been necessary, which was not feasible. Second, the
profunda femoris vein was not studied separately, although
this vein may play an important role as part of the collateral
circulation. Inflow from the profunda may prevent
thrombus extension from the femoral vein centrally or, if
not involved, establish a compensatory outflow channel in
the future.22 Third, no distinction was made between calf
vein thrombosis of the peroneal, posterior and anterior
tibial veins and muscular calf vein thrombosis, or between
DVT in a single calf vein and in multiple deep calf veins. This
could have provided interesting data about their frequency
of occurrence in this large cohort. It should also be
acknowledged that the accuracy of DUS in delineating the
central extent of the thrombus in the CIV and IVC may have
been limited in certain patients. The involvement of the EIV,
that is, extension above the inguinal ligament, was always
evaluated, which is sufficient for the present analysis.
In conclusion, patients with an acute lower limb DVT
should have a thorough mapping of the thrombus local-
isation by DUS rather than a simple subdivision into “distal”
and “proximal” DVT. The results of detailed mapping illus-
trated the large diversity of thrombus distribution in pa-
tients previously described as having a “proximal DVT”.
Therefore this entity should be abandoned and replaced by
iliofemoral and femoropopliteal DVT. The study also con-
firms that a substantial number of patients with DVT (38%
in the present cohort) present with iliofemoral DVT. This
finding allows differentiation of treatment as per guide-
lines.8 In practice, as many as 12% of patients with DVT
would be ideal candidates for early clot removal, based on
DUS findings.
CONFLICT OF INTEREST
None.
FUNDING
None.
ACKNOWLEDGEMENTS
We would like to thank the vascular technologists and
vascular surgeon colleagues, active in the Department of
Thoracic and Vascular Surgery of the Antwerp University
Hospital between 1994 and 2012, for having carefully
registered the extent of DVT on a diagram for every patient.
This study was presented at the 14th annual meeting of
the European Venous Forum (EVF) in Belgrade (Serbia) in
June 2013 by Niels Bochanen (winner of 3rd EVF prize).
6 M.G.R. De Maeseneer et al.

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Please cite this article in press as: De Maeseneer MGR, et al., Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports
the Inadequacy of the Term “Proximal DVT”, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.11.001