Blood Coagulation, Fibrinolysis and Cellular Haemostasis © Schattauer 2011 31

Predictive factors for concurrent deep-vein thrombosis and

symptomatic venous thromboembolic recurrence in case of superficial
venous thrombosis
The OPTIMEV study
Jean-Philippe Galanaud1,2; Celine Genty3,4; Marie-Antoinette Sevestre3,4,5; Dominique Brisot1,6; Michel Lausecker7; Jean-Luc Gillet8;
Carole Rolland3,4; Marc Righini9; Georges Leftheriotis10; Jean-Luc Bosson3,4; Isabelle Quere1,2; the OPTIMEV SFMV investigators*
1Vascular medicine unit, Department of internal medicine, University Hospital, Montpellier, France; 2Research Unit EA2992, Montpellier 1 University, Montpellier, France;
3Techniques de l’Ingénierie Médicale et de la Complexité (TIMC), Unité Mixte de Recherche 5525, Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier,
Grenoble, France; 4Clinical Investigation Center, University Hospital, Grenoble, France; 5Vascular medicine Unit, Amiens University Hospital, Amiens, France; 6Vascular medicine
physician, Clapiers, France; 7Vascular medicine physician, Selestat, France; 8Vascular medicine physician, Bourgoin-Jallieu, France; 9Division of Angiology and Haemostasis, Geneva
University Hospital, Geneva, Switzerland; 10Vascular Medicine Unit, University Hospital, Angers, France

Summary varicose SVTs (1.4% vs. 1.1%; 3.4% vs. 2.8%; 0.7% vs. 0.3%). Only
Superficial venous thrombosis (SVT) prognosis is debated and its man- male gender (OR=3.5 [1.1–11.3]) and inpatient status (OR=4.5

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agement is highly variable. It was the objective of this study to assess
predictive risk factors for concurrent deep-vein thrombosis (DVT) at
presentation and for three-month adverse outcome. Using data from
the prospective multicentre OPTIMEV study, we analysed SVT predic-
tive factors associated with concurrent DVT and three-month adverse
outcome. Out of 788 SVT included, 227 (28.8%) exhibited a concurrent
DVT at presentation. Age >75years (odds ratio [OR]=2.9 [1.5–5.9]), ac-
tive cancer (OR=2.6 [1.3–5.2]), inpatient status (OR=2.3 [1.2–4.4]) and
SVT on non-varicose veins (OR=1.8 [1.1–2.7]) were significantly and in-
dependently associated with an increased risk of concurrent DVT.
39.4% of SVT on non-varicose veins presented a concurrent DVT. How-
ever, varicose vein status did not influence the three-month prognosis
as rates of death, symptomatic venous thromboembolic (VTE) recur-
rence and major bleeding were equivalent in both non-varicose and
[1.3–15.3]) were independent predictive factors for symptomatic VTE
recurrence but the number of events was low (n=15, 3.0%). Three-
month numbers of deaths (n=6, 1.2%) and of major bleedings (n=2,
0.4%) were even lower, precluding any relevant interpretation. In con-
clusion, SVT on non-varicose veins and some classical risk factors for
DVT were predictive factors for concurrent DVT at presentation. As SVT
remains mostly a clinical diagnosis, these data may help selecting pa-
tients deserving an ultrasound examination or needing anticoagulation
while waiting for diagnostic tests. Larger studies are needed to evaluate
predictive factors for adverse outcome.
Keywords
Superficial vein thrombosis, thrombophlebitis, deep-vein thrombosis,
pulmonary embolism, varicose veins

Correspondance to: Financial support:

Jean-Philippe Galanaud The study was funded by a grant from the Hospital Clinical Research Program of the
Service de Médecine Interne et Maladies Vasculaires French Ministry of Health and a grant from Sanofi-Aventis. This study was supported
Hôpital Saint Eloi, Centre Hospitalier Universitaire de Montpellier by the French Society of Vascular Medicine (SFMV). All investigators are members of
80, avenue Augustin Fliche, 34295 Montpellier Cedex 05, France the SFMV.
Tel: +33 467 33 70 24, Fax: +33 467 33 70 23 Received: June 25, 2010
E-mail: jp-galanaud@chu-montpellier.fr Accepted after minor revision: September 10, 2010
Prepublished online: September 30, 2010
* A list of the OPTIMEV SMFV Study investigators is available online at doi:10.1160/TH10-06-0406
www.thrombosis-online.com. Thromb Haemost 2011; 105: 31–39

Introduction So far, SVT management is debated as suggested by the low

Superficial venous thrombosis (SVT) is a frequent event, with a
higher prevalence than deep-vein thrombosis (DVT) (1, 2). How-
ever, as compared with DVT, SVT has been dramatically less
studied, leading to numerous uncertainties about its epidemiology
and management (3, 4). Moreover, SVT is mainly a primary care
disease, whose diagnosis is often based on clinical presentation
only. The perceived benign prognosis of SVT may explain under-
reporting and the scarcity of available data.
grade of recommendation (Grade 2B) of the last American College
of Chest Physicains (ACCP) guidelines (3, 5, 6). Indeed, the last
large randomised multicenter trials failed to evidence statistically
significant differences between treatments (placebo, non-steroidal
anti-inflammatory drugs, different regimens of anticoagulants) (7,
8). The POST study suggested that, among patients with sympto-
matic SVT at inclusion, 25% also had symptomatic DVT and/or
pulmonary embolism (PE) (9). More recently, results of the CAL-
ISTO trial suggested a superiority of fondaparinux at prophylactic

Thrombosis and Haemostasis 105.1/2011

32 Galanaud et al. SVT and concurrent DVT
dose over placebo to prevent any kind of venous thromboembolic
(VTE) outcomes in presence of isolated SVT (10). It appears there-
fore that SVT might not be an entirely benign condition. As the po-
tential gravity of SVT is probably mainly related to the concomi-
tant presence of DVT, the detection of predictive factors associated
with the presence of concurrent DVT could be useful to guide both
diagnostic and therapeutic approach (11, 12). Therefore, we used
the OPTIMEV (OPTimisation de l’Interrogatoire dans l’évalu-
ation du risque throMbo-Embolique Veineux) study database to
compare, among patients referred for a suspicion of symptomatic
SVT, the risk factors profile of patients with isolated SVT to those
with SVT associated with DVT at presentation. We then analysed
the three-month outcome (death, VTE recurrence, major bleed-
ing) and the predictive factors for adverse outcome of isolated SVT.
Materials and methods
The OPTIMEV study is a large, French, multicentre, prospective,
epidemiological, observational study of in- and outpatients re-
ferred for clinically suspected VTE (DVT, PE, SVT) to vascular
medicine physicians (13, 14). In this sub-study we focused on pa-
tients with symptomatic SVT. The study protocol has been exten-
sively described elsewhere (13, 14). It is available on Clinical-
Trials.gov (registration number: NCT00670540).
Patients
Between November 2004 and January 2006, 8256 patients aged at
least 18 years referred for clinically suspected VTE (DVT, PE, SVT),
to the vascular medicine physicians of the 41 hospitals and 292 pri-
vate practices participating in the study, were enrolled (씰Fig. 1).
All elegible patients with a suspicion of symptomatic DVT/SVT of
the lower limbs underwent a comprehensive real-time B-mode
and colour Doppler ultrasonography (US) examination of both
legs by a vascular medicine physician. The following veins were
scanned transversally over their entire length: inferior vena cava,
iliac veins, femoral veins, popliteal veins, anterior and posterior ti-
bial veins, fibular veins, medial and lateral gastrocnemius veins, so-
leal veins, the sapheno-femoral/popliteal junctions, the trunk of
the great and small saphenous veins and wherever thrombosis was
clinically suspected. Diagnosis of DVT or SVT was confirmed if
there was incompressibility of the vein. The diagnosis of PE was
confirmed according to the PIOPED criteria and after validation
by an independent expert committee (15, 16).
For the present sub-study, we only took into account patients
with objectively confirmed SVT (with or without DVT/PE), se-
lected among patients referred to their vascular medicine phys-
icians for a suspicion of symptomatic SVT.
Thrombosis and Haemostasis 105.1/2011
Study protocol
This study had a cross-sectional and a prospective design. At inclu-
sion, all demographic characteristics, clinical data, diagnostic tests
results were prospectively collected by the vascular medicine phys-
ician. At three months, patients were asked by phone by clinical re-
search associates to disclose all health-related events since inclu-
sion. These investigations were conducted for all patients with VTE.
The general practitioner or the vascular medicine physician was
contacted whenever a possible event was disclosed, or when history
taking did not seem fully reliable. Medical records were reviewed in
case of hospitalisation or another visit to the vascular medicine
physician during this follow-up period. For practical reasons, pa-
tients who were enrolled in overseas territories, living outside of
France, who were homeless, or for whom case-report form comple-
tion was delayed were not eligible for follow-up. Quality of data was
monitored electronically. In case of inconsistency, clinical research
associates were in charge of comparing the medical records with
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those transferred online (phone call or visit to the investigating
centre). An independent expert committee adjudicated all sus-
pected adverse event after analysis of medical records. The study
was approved by the Ethics Committee (Comité Consultatif sur le
Traitement de l’Information en matière de Recherche dans le do-
maine de la Santé) and the CNIL (Commission Nationale de l’In-
formatique et des Libertés). All patients received written informa-
tion explaining the study objectives and were informed that they
could decline telephone follow-up and could consult their data.
Clinical symptoms at presentation
The lower limbs clinical symptoms of DVT/SVT screened were
swelling, dull pain, warmth and localised pain with palpable tender
cord in the course of a superficial vein.
Risk factors
The influence of the following potential risk factors for VTE was
analysed: age, gender, inpatient or outpatient status, and anti-
coagulant treatment at inclusion. Chronic risk factors for VTE
studied were: a personal or a family history of VTE, active cancer,
oestrogen therapy within the last two months and obesity (body
mass index ≥30 kg/m2). A varicose vein was defined according to
the clinical component of the CEAP classification (C≥2), in ac-
cordance with the last consensus statement (17). Transient risk fac-
tors analysed were: bed confinement, recent plaster immobili-
sation of the lower extremities, recent travel (i.e. travel longer than
3 hours in the last month), surgery within the previous 45 days,
congestive heart failure (NYHA class III or IV) or respiratory in-
sufficiency (acute respiratory failure or exacerbation of chronic
obstructive pulmonary disease), infectious disease, and pregnancy
or recent childbirth (i.e. early post-partum <6 weeks).
© Schattauer 2011
 Galanaud et al. SVT and concurrent DVT 33

Study outcomes Statistical analysis

The study outcomes were recurrent VTE, major bleeding and over-
all mortality at three months. All recurrent VTE were confirmed
objectively as indicated above. Major bleeding episodes were fatal
bleeding and overt bleeding within a critical organ (e.g. intracran-
ial, retroperitoneal, intraocular, pericardial, intraspinal or in ad-
renal glands) or associated with a fall in haemoglobin level >2g/dl,
or leading to a transfusion >2 units of packed red blood cells or
whole blood. An independent expert committee adjudicated all the
clinical outcomes.
Categorical variables were expressed as frequency and percentage;
continuous variables were expressed as median and interquartile
range (IQR). In univariate analyses, potential risk factors for VTE,
three-month adverse outcomes and their predictive factors were
estimated using a Chi2 test for categorical variables (or a Fisher test
when necessary) and using Mann-Whitney test for continuous
variables. A multivariate logistic regression was performed to esti-
mate the adjusted odds ratios (OR) and corresponding 95% con-
fidence interval (CI) associated with each risk factor for SVT with
concurrent DVT vs. isolated SVT. The independent covariates en-
tered into the logistic regression models included age, gender,
clinical symptoms at presentation, risk factors for VTE, inpatient
versus outpatient status, and the use of anticoagulant therapies at

Table 1: Patient char-

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Characteristics Isolated SVT SVT + DVT SVT+DVT
acteristics at baseline, vs. SVT
clinical symptoms and OR 95% [CI]
risk factors for SVT
n (%) 556 (71) 227 (29) -
with concurrent DVT
†
versus isolated SVT Age (years), median (IQR) 63 (49 – 74) 70 (57 – 77) –
(univariate and multi- Age ≤50, n (%) 153 (28) 36 (16)† Ref
variate analyses). Age [51 – 75], n (%) 295 (53) 122 (54)† 1.8 [1.0 – 3.4]
Age > 75, n (%) 108 (19) 69 (30)† 2.9 [1.5 – 5.9]*
Men, n (%) 188 (34) 93 (41) 1.2 [0.8 – 1.9]
† 2.3 [1.2 – 4.4]*
Inpatients, n (%) 63 (11) 59 (26)
Anticoagulant treatment at inclusion, n (%) 81 (15) 24 (11) 0.4 [0.2 – 0.8]*
Clinical symptoms at presentation
Oedema, n (%) 183 (33) 112 (49)† 2.4 [1.5 – 3.8]†
Dull pain, n (%) 132 (24) 98 (43)† 2.6 [1.6 – 4.2]†
Localised pain, with palpable cord, n (%) 451 (81) 128 (56)† 0.5 [0.3 – 0.7]*
*
Warmth, n (%) 200 (36) 65 (29) 0.6 [0.4 – 1.0]
Transient risk factors for venous thromboembolism
Bed confinement, n (%) 29 (5) 23 (10)* 1.4 [0.6 – 3.2]
Recent plaster immobilisation of the lower limb(s), n (%) 3 (1) 0 (0) -¶
Recent travel, n (%) 21 (4) 10 (4) 1.4 [0.5 – 3.9]
Recent surgery (≤45 days), n (%) 44 (8) 17 (7) 0.6 [0.3 – 1.4]
Congestive heart failure or respiratory insufficiency, n (%) 21 (4) 9 (4) 0.6 [0.2 – 1.9]
Acute infectious disease, n (%) 6 (1) 3 (1) 0.4 [0.1 – 2.6]
Pregnancy or post partum < 6 weeks, n (%) 23 (4) 2 (1)* 0.1 [0.1 – 0.9]*
Chronic risk factors for venous thromboembolism
Personal history of DVT or PE, n (%) 212 (38) 101 (44) 1.2 [0.8 – 1.8]
Family history of DVT or PE, n (%) 100 (18) 46 (20) 1.4 [0.8 – 2.3]
Active cancer, n (%) 28 (5) 37 (16)† 2.6 [1.3 – 5.2]*
†
Non-varicose veins, n (%) 168 (30) 109 (48) 1.8 [1.1 – 2.7]*
Oral contraception, n (%) 23 (4) 8 (4) 1.2 [0.4 – 4.2]
Hormone replacement therapy, n (%) 11 (2) 3 (1) 1.4 [0.3 – 6.5]
Obesity (BMI > 30 kg/m2), n (%) 91 (16) 36 (16) 1.1 [0.6 – 1.9]
*p<0.05; †p<0.001. ¶: variable not kept in the multivariate model because of insufficient size.

© Schattauer 2011 Thrombosis and Haemostasis 105.1/2011

34 Galanaud et al. SVT and concurrent DVT
the time of enrolment. To account for patient clustering within en-
rolling physician practices, random intercept logistic regression
models with the two levels defined by patient and physician were
used. The influence of each risk factor present at inclusion on the
occurrence of three-month VTE recurrence risk was evaluated
with Cox models, adjusted on anticoagulant treatment duration.
Two-sided p values of 0.05 or less were considered as statistically
significant. Statistical analyses were performed using Stata soft-
ware (version 10.0, Stata Corp, College Station, TX, USA).
Results
Population characteristics
Out of a total of 8256 patients with a suspicion of VTE enrolled be-
tween November 2004 and January 2006, 1435 (17.4%) patients
presented a suspicion of SVT that was confirmed in 788 cases
(9.5% of all patients). Among SVT patients, median age (IQR) was
65 years (51 – 75); 35.9% (n=283) were men and 15.9% (n=125)
were inpatients (씰Fig. 1, Table 1).
Thrombosis and Haemostasis 105.1/2011
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Figure 1: Patient en-
rolment and follow-up.
Comparison between isolated SVT and SVT
associated with DVT at presentation
Among the 788 SVT, 227 (28.8%) were associated with a DVT, dis-
tributed as follows:
● DVT without PE: 178 cases (78.4%) of which, 114 (64.0%) were
distal DVT.
● DVT with PE: 49 cases (21.6%) of which, 14 (28.6%) were dis-
tal DVT.
SVT with PE but without DVT accounted for only 2.2% (5/232) of
all SVT with DVT or PE.
The exact localisation of DVT is missing in 12 cases of DVT: six
in the DVT without PE group and six in the PE group.
The time lag between the onset of symptoms and the realisation
of the compression ultrasonography was equivalent between iso-
lated SVT and SVT with DVT, both with a median of four days,
(IQR 3–8 days).
Superficial venous location of thrombus
Among the 734 patients with SVT but without PE – exact locali-
sation of SVT was not transferred in the case report form in case of
© Schattauer 2011
 Galanaud et al. SVT and concurrent DVT 35

Table 2: Clinical outcomes at three months Patients with isolated SVT Patients with SVT + DVT
in patients with isolated SVT and in pa-
n/N %, 95% [CI] n/N %, 95% [CI]
tients with SVT + DVT at presentation.
Recurrent VTE 15/499 3.0 [1.7 – 4.9] 11/204 5.4 [2.7 – 9.4]
– SVT 9/499 1.8 [0.8 – 3.4] 4/204 2.0 [0.5 – 4.9]
– DVT 3/499 0.6 [0.1 – 1.8] 1/204 0.5 [0.01 – 2.7]
– PE 3/499 0.6 [0.1 – 1.8] 6/204 2.9 [1.1 – 6.3]
Major bleeding 2/499 0.4 [0.1 – 1.4] 3/204 1.5 [0.3 – 4.2]
Death 6/499 1.2 [0.4 – 2.6] 19/204 9.3 [5.7 – 14.2]†
P-values in patients with isolated SVT vs. patients with SVT + DVT: *p≤0.05; †p<0.001.

PE (with/without DVT) – in 68.1% (n=500) of cases, the SVT af-
fected the great saphenous vein, in 16.9% (n=124) the small sa-
phenous vein and in 29.0% (n=213) another vein (a given patient
could have several SVTs).
As compared with isolated SVT, SVT associated with DVT but
without PE affected statistically significantly more often the calf re-
p<0.001), but similar rates of VTE recurrence and of major bleed-
ing (씰Table 2).
Anticoagulant treatment
Among patients with isolated SVT followed up, 76.4% (381/499)

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gion or the sapheno-femoral/sapheno-popliteal junctions – as
compared with the thigh – (56.3% vs. 48.8% and 24.7% vs. 12.3%,
respectively, p<0.001) and the small saphenous vein (29.2% vs.
12.9%, p<0.001).
Clinical symptoms at presentation
Localised pain was significantly more associated with isolated SVT,
whereas oedema and dull pain were significantly more associated
with SVT with concurrent DVT (씰Table 1).
were treated with anticoagulant drugs and 24.6% (123/499) were
treated at least 45 days (씰Table 3).
Among patients with SVT with a concurrent DVT followed up,
93.5% (187/200) were treated with anticoagulant drugs and 83.5%
(167/200) were treated for more than 45 days (씰Table 3).
Predictive factors for three-month adverse event in case
of isolated SVT at presentation
● Symptomatic VTE recurrence (n=15)

Only inpatient status and male gender were found to be indepen-

dent predictive factors for three-month symptomatic VTE recur-
Risk factors profile rence (씰Table 4).
Presence of non-varicose veins, age >75 years, inpatient status and ● Symptomatic PE or DVT events (n=6)

active cancer were statistically more associated with SVT with DVT ● Death (n=6)

whereas anticoagulant treatment at inclusion and pregnancy or ● Major bleeding (n=2)

post-partum (and presence of varicose veins) were significantly

and independently more associated with isolated SVT (씰Table 1). To prevent irrelevant interpretations, because of the very low
Similar results were found when one compares isolated SVT with number of events, we did not perform analyses of predictive fac-
SVT with DVT or PE (i.e. including SVT with PE but without tors for these adverse events.
DVT).

Table 3: Anticoagulant treatment administered according to the kind

Association of clinical symptoms of SVT followed up.
The association of a localised pain, varicose veins and absence of Isolated SVT SVT + DVT
oedema and dull pain – independent predictive factors for absence n (%) n (%)
of concurrent DVT – was present in 27.6% of all SVT (n=216) and n=499 n=200*
a concurrent DVT was evidenced in 14.8% (32/216) of cases. On No anticoagulant treatment 118 (23.6%) 13 (6.5%)
contrary, in case of association of oedema, dull pain on non-vari- Anticoagulant treatment 381 (76.4%) 187 (93.5%)
cose veins without localised pain and palpable cord (n=35, 4.5% of
LMWH only 267 (70.1%) 18 (9.0%)
all SVT), a concurrent DVT was present in up to 65.7% of cases – Prophylactic regimen 11 (4.1%) 1 (5.6%)
(23/35). – Full therapeutic dose 247 (92.5%) 17 (94.4%)
– Unknown dose 9 (3.4%) -

Three-month clinical outcomes LMWH + VKA 114 (29.9%) 162 (81.0%)

Unknown anticoagulant - 7 (3.5%)
As compared with isolated SVT patients, patients with SVT with
concurrent DVT presented a higher risk of death (9.3% vs. 1.2%, *Data on anticoagulant treatment is missing in four patients (4/204).

© Schattauer 2011 Thrombosis and Haemostasis 105.1/2011

36 Galanaud et al. SVT and concurrent DVT

Comparison between SVT on varicose veins and SVT Three-month outcome

on non-varicose veins at presentation
A total of 506 (64.6%) SVT occurred on varicose veins (and 277 on
non-varicose veins). SVT on non-varicose veins was significantly
more frequently associated with a concurrent DVT or a PE than
SVT on varicose veins (39.4% vs. 23.3%, p<0.001).
Risk factors profile
Among patients with isolated SVT, univariate analysis evidenced
that congestive heart failure or respiratory insufficiency and male
gender were significantly more associated with SVT on non-vari-
cose veins (6.5% vs. 2.6%, and 42.9% vs. 29.9%, respectively, both
p≤0.05), only the latter risk factor remaining statistically signifi-
cant in multivariate analysis (OR=2.1 [1.3 – 3.4]).
There was no statistically significant difference between isolated
SVT on non-varicose veins and isolated SVT on varicose veins in
terms of death (1.4% vs. 1.1%), major bleeding (0.7% vs. 0.3%)
and VTE recurrence (3.4% vs. 2.8%). In the latter case, isolated
SVT on non-varicose veins were more associated with sympto-
matic DVT or PE recurrence (2.7% vs. 0.6%) but this result did not
reach statistical significance (p=0.07).
When one considers the whole cohort of SVT with or without
DVT/PE at presentation, SVT on non-varicose veins were statisti-
cally more associated with three-month risk of death (7.4% vs.
1.5%, p<0.001), major bleeding (1.7% vs. 0.2%, p=0.05) but not
VTE recurrence (4.2% vs. 3.5% p=0.65).

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Characteristics Isolated SVT SVT + DVT/PE/ SVT+ DVT/PE/ Table 4: Predictive
(N=484) SVT SVT vs. SVT factors for three-
(n=15) OR 95% [CI] month symptomatic
VTE event (SVT, DVT or
Age ≤50, n (%) 130 (27) 3 (20) Ref
PE) in case of isolated
Age [51 – 75], n (%) 254 (52) 9 (60) 2.2 [0.5 – 10.6] SVT (univariate and
Age > 75, n (%) 100 (21) 3 (20) 2.2 [0.3 – 14.1] multivariate analyses).
Men, n (%) 157 (32) 8 (53) 3.5 [1.1 – 11.3]*
Inpatients, n (%) 56 (12) 5 (33)* 4.5 [1.3 – 15.3]*
Anticoagulant treatment
none 117 (24) 1 (7) Ref
≤10 days, n (%) 104 (21) 4 (27) 3.9 [0.4 – 36.2]
11 – 30 days, n (%) 106 (22) 7 (47) 4.9 [0.6 – 41.6]
> 30 days, n (%) 157 (32) 3 (20) 1.3 [0.1 – 13.1]
Transient risk factors for venous thromboembolism
Bed confinement, n (%) 24 (5) 1 (7) 0.6 [0.1 – 5.9]
Recent plaster immobilisation of the lower limb(s), n (%) 1 (0.2) 0 (0) -¶
Recent travel, n (%) 18 (4) 0 (0) -¶
Recent surgery (≤45 days), n (%) 40 (8) 0 (0) -¶
Congestive heart failure or respiratory insufficiency, n (%) 20 (4) 0 (0) -¶
Acute infectious disease, n (%) 6 (1) 0 (0) -¶
Pregnancy or post partum < 6 weeks, n (%) 20 (4) 1 (7) 2.4 [0.2 – 31.6]
Chronic risk factors for venous thromboembolism
Personal history of DVT or PE, n (%) 189 (39) 8 (53) 2.1 [0.7 – 6.3]
Family history of DVT or PE, n (%) 88 (18) 4 (27) 1.6 [0.5 – 5.2]
Active cancer, n (%) 26 (5) 1 (7) 1.1 [0.1 – 10.0]
Non-varicose veins, n (%) 142 (29) 5 (33) 1.0 [0.3 – 3.1]
Oral contraception, n (%) 22 (5) 0 (0) -¶
Hormone replacement therapy, n (%) 10 (2) 0 (0) -¶
Obesity (BMI > 30 kg/m2), n (%) 81 (17) 4 (27) 1.2 [0.4 – 4.2]
†
*p<0.05; p<0.001. ¶: variable not kept in the multivariate model because of insufficient size.

Thrombosis and Haemostasis 105.1/2011 © Schattauer 2011


Discussion
Our study confirms that SVT might not be a totally benign con-
dition as 29% of patients with SVT also had a DVT. Among our
population of in- and outpatients with symptomatic SVT, lower
limb oedema, dull pain, SVT on non-varicose veins, age >75 years,
active cancer and inpatient status are predictive factors for the
presence of a concurrent DVT. In case of isolated SVT, male gender
and inpatient status are predictive factors for three-month symp-
tomatic VTE recurrence.
In case of symptomatic SVT, some local and general conditions/
symptoms are associated with the presence of a concurrent DVT at
presentation. Among the general conditions associated with the
presence of a DVT, classical strong risk factors for DVT/PE, re-
sponsible of a global pro-thrombotic state are retrieved: active
cancer, elevated age and inpatient status (6, 14). Local conditions
are mainly anatomical. Thus, as compared with SVTs affecting the
thigh region, those affecting the sapheno-femoral/popliteal junc-
tions and the calf are significantly more associated with the pres-
ence of a concomitant DVT. This is consistent with previous
studies and can be explained by a greater closeness to the deep ve-
nous system and by a higher number of perforating veins at the calf
level, respectively (12, 18). Another important local risk factor evi-
denced is the occurrence of SVT on non-varicose veins (OR=1.8
[1.1 – 2.7]). In OPTIMEV, 39.4% of SVT on non-varicose veins had
a concurrent DVT, which is comparable to the 44% of Bergqvist's
study including 56 consecutive patients (11).
However, the risk of concomitant DVT associated with SVT on
varicose veins is far from being negligible (23.3%). Furthermore,
in case of presence of all predictive clinical factors for isolated SVT
(localised pain on varicose veins without dull pain and oedema) a
concurrent DVT was still present in almost 14% of cases. There-
fore, physical examination is probably not sufficient to exclude
such an association, suggesting that in presence of clinical SVT, ad-
ditional investigations like ultrasound are warranted.
Our results suggest also that SVT early management – in par-
ticular diagnostic procedure or potential initiation of anticoagu-
lant treatment before diagnostic confirmation – might be in part
modulated according to the varicose veins status. Specific trials in
this field are needed.
As previously discussed, varicose vein status is important to
evaluate the risk of concurrent DVT at presentation. Moreover, it
has also been reported to be a predictive factor for adverse outcome
(9, 19–21). In our study, the three-month risk of death of SVT on
non-varicose veins is significantly higher than that of SVT on vari-
cose veins (7.4% vs. 1.5%, p<0.001). However, this latter result
must be balanced by the presence of a concurrent DVT at presen-
tation. Thus isolated SVT on non-varicose veins three-month ad-
verse outcome is equivalent to isolated SVT on varicose veins one
in terms of death (1.4% vs. 1.1%), VTE recurrence (3.4% vs. 2.8%)
and major bleeding (0.7% vs. 0.3%). Multivariate analysis did not
evidence any influence of varicose vein status (OR=1.0 [0.3 – 3.1])
on the VTE risk of recurrence of isolated SVT. We could only con-
firm the predictive role of male gender and of inpatient status on
VTE recurrence. Although the number of symptomatic VTE
© Schattauer 2011
Galanaud et al. SVT and concurrent DVT 37
events (n=15) was sufficient to analyse potential predictive factors,
interpretation of such results must be cautious and we may have
lacked of statistical power.
Our study presents a number of strengths and limitations.
Among its strengths, the large number of SVT included, the pros-
pective and multicenter design with an in- and outpatient recruit-
ment and the low rate of lost to follow-up (less than 1%) should be
pointed out. The history taking and the evaluation of venous
status, key elements in the determination of our predictive factors
for adverse events, were done by well-trained vascular medicine
physicians. In OPTIMEV, there was no medical exclusion criterion
and every physician was free to manage his patients as he used to
do; therefore, our results reflect the prognosis of SVT, addressed to
vascular medicine physicians, in the French real-life. As expected,
isolated SVT early prognosis is good with a low incidence of three-
month adverse events (7–9), which have possibly precluded iden-
tifying predictive factors for adverse events like non-varicose veins
or active cancer. On the contrary, the early prognosis of SVT with
Downloaded by: Universiteit Leiden / LUMC. Copyrighted material.
concurrent DVT, was comparable to that of symptomatic DVT or
PE (22, 23).
Among the limitations of our study we are aware that SVT is
mainly a primary-care pathology. However, only 15% of our in-
cluded patients were inpatients. Whether or not this reflects the
real French distribution of SVT might be a matter of debate. We
cannot exclude that primary-care physicians have only addressed
to us their patients at highest risk of DVT, the consequence being
an overestimation of the rate of concurrent DVT. Such a potential
bias is difficult to evaluate. However our 29% rate of concurrent
DVT is comparable to the one reported in the most recent studies
(9, 12). Furthermore, our analyses of predictive factors for adverse
events were all adjusted by in- and outpatient status and by centre.
This should have controlled such potential recruitment bias.
Our rate of three-month symptomatic VTE event is lower than
in POST and STENOX studies (3.0% vs. more than 10% in both
studies) (7, 9). Such a difference probably reflects differences in in-
clusion criteria, study design and therapeutic management. In
POST and STENOX studies only thrombi longer than 5cm, at high
VTE risk, were included and a systematic ultrasonographic exam-
What is known about this topic?
● Superficial vein thrombosis (SVT) prognosis is debated and its
management is highly variable.
● SVT on non-varicose veins could be a risk factor for adverse events
(death, venous thromboembolism [VTE] recurrence and bleeding).
What does this paper add?
● In case of suspicion of symptomatic SVT, the rate of concurrent
deep-vein thrombosis (DVT) can be as high as 28%.
● As compared with SVT on varicose vein, SVT on non-varicose vein
is a strong risk factor for concurrent DVT at presentation. However,
in case of isolated SVT, SVT on non-varicose vein is not associated
with a higher risk of three-month adverse outcome (death, VTE re-
currence and bleeding).
Thrombosis and Haemostasis 105.1/2011
38 Galanaud et al. SVT and concurrent DVT
ination was performed at least at day 10, which may have favoured
the discovery of poorly symptomatic VTE. On the contrary, in the
OPTIMEV study, patients received anticoagulant drugs for longer
periods and with higher intensity regimen. Furthermore, tele-
phone supervision by clinical research associates may have favour-
ed underreporting of VTE events. As the discovery of a DVT or a
PE strongly modifies the prognosis and the therapeutic manage-
ment it seems to us unlikely that a significant number of patients –
and vascular medicine physician or general physician when the
history taking did not seem fully reliable – forgot to disclose it.
However, we can not exclude the possibility that SVT extension or
recurrence may have been underreported, as it does not dramati-
cally alter SVT management. We therefore may have underesti-
mated the rate of symptomatic SVT recurrence. As all events were
adjudicated by an independent expert committee after analysis of
the medical report an overestimation is improbable. Lastly, the low
numbers of three-month symptomatic DVT/PE events (n=6),
deaths (n=6) and major bleedings (n=2) preclude from drawing
any conclusion about predictive factors for these adverse out-
comes.
In conclusion, our study evidences that SVT occurring on non-
varicose veins, the presence of an active cancer and inpatient status
are frequently associated with concurrent DVT at presentation. As
SVT remains mostly a clinical diagnosis in everyday practice, these
data may help in selecting patients requiring ultrasound examin-
ation, or identifying patients needing anticoagulation while wait-
ing for diagnostic tests. Larger studies or meta-analyses are needed
to reach a sufficient statistical power in identifying and quantifying
predictive factors for adverse events.
Acknowledgements
The authors are indebted to Catherine Blanie, Maryline Blanc, Ma-
rion Proust, Sandrine Massicot, Ludovic Delhomme, Cathy Mail-
lard, Caroline Bonnet for data monitoring and patients follow-up.
Conflict of interest
Prof. J. L. Bosson and Dr. M. A. Sevestre have been paid consult-
ing fees for presenting OPTIMEV results by Sanofi-Aventis com-
pany.
Appendix
Expert Event Committee:
Muriel Salvat, Christophe Seinturier, Gilles Pernod, José Labarère, San-
dra David-Tchouda, Jacqueline Yver, Bernadette Satger, Anna Arsla-
nian, Michele Fontaine, Olivier Pichot, Sophie Blaise, Mario Maufus,
Marie-Agnès Ningres, Pierre Casez and Elodie Sellier.
Study Coordinating Centre:
Clinical Research Center, University Hospital, Grenoble, France.
Thrombosis and Haemostasis 105.1/2011
Abbreviations
BMI, body mass index; CI, confidence interval; DVT, deep-vein throm-
bosis; IQR, interquartile range, LMWH, low-molecular-weight heparin;
OR, odds ratio; PE, pulmonary embolism; SVT, superficial vein throm-
bosis; VKA, vitamin K antagonist; VTE, venous thromboembolism.
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