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146
J.A. Caprini and M.J. Verta
Table 15.2 Summary of SVT treatment studies
Study Design Interventions Measured outcomes Results
Prandoni (2005) [
50 ] RCT Prophylactic dose nadroparin
(n = 81)
VTE and/or SVT extension by
DUS at 3 months
8.6% with prophylactic dose
Therapeutic dose nadroparin
(n = 83)
7.2% with therapeutic dose ( P = .74)
Both for 30 days No major bleeding
Gorty (2004) [
62 ] Retrospective chart review Surgery (n = 15) VTE and/or SVT recurrence by
DUS at a mean follow up of
73.71 days
0% with surgery
Anticoagulation (n = 21) 29% with anticoagulation
No anticoagulation (NSAIDs,
compression, n = 24)
46% without anticoagulation ( P < .04
vs with anticoagulation)
STENOX (2003) [
4 ] RCT Placebo (n = 111) Primary endpoint: VTE (DVT by
DUS or symptomatic PE) at day 12
Primary endpoint:
Enoxaparin 40 mg (n = 109) Secondary endpoint: VTE and/or
SVT recurrence or extension at day
12
Placebo = 3.6%
Enoxaparin 1.5 mg/kg (n = 102)
Enoxaparin 40 mg = 0.9% ( P = .37)*
Tenoxicam (n = 94) Enoxaparin 1.5 mg/kg = 1%
( P = .37)*
All once daily for 8–12 days
Tenoxicam = 2.1% ( P = .69)*
Secondary endpoint:
Placebo = 30.6%
Enoxaparin 40 mg = 8.3%
( P < .001)*
Enoxaparin 1.5 mg/kg = 6.9%
( P < .001)*
Tenoxicam = 14.9% ( P < .01)*
No death or major hemorrhage
Lozano (2003) [
35 ] Randomized, open Surgery (saphenofemoral
disconnection) + compression
(n = 45)
DVT and/or symptomatic PE PE occurred in 6.7% of patients with
surgery vs 0 patients with enoxaparin
Enoxaparin + compression for
4 weeks (n = 39)
SVT extension or recurrence SVT recurrence was 3.3% with
surgery vs 10% with enoxaparin
Complications of the surgical wound
occurred in 6.7% of patients
Minor bleeding occurred in 6.7% of
patients with enoxaparin
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14715 Super fi cial Vein Thrombosis
Study Design Interventions Measured outcomes Results
Ascher (2003) [
34 ] Retrospective chart review NSAIDs (patients with SVT,
n = 11)
SVT resolution using DUS at
18 months
81% of patients with SVT/DVT had
complete resolution with
UFH + warfarin
UFH (aPTT 2.0–2.5 times control)
followed by warfarin for 6 months
(patients with SVT + DVT, n = 21)
43% of patients with SVT had
complete resolution with NSAIDs
Marchiori (2002) [
32 ] RCT High-dose UFH (12,500 IU for
1 week, 10,000 IU for 4 weeks;
n = 30)
Symptomatic or asymptomatic
DVT or symptomatic PE at
6 months
20% with low-dose UFH
Low-dose UFH (5,000 IU for
4 weeks; n = 30)
3.3% with high-dose UFH ( P = .05)
Beatty (2002) [
39 ] Open Surgery (emergency division of the
sapheno-femoral junction) + UFH
for 5 days (n = 17)
VTE or SVT recurrence or
extension at 2 months
No patient had thrombus propagation
or PE
One patient developed a nonocclusive
thrombus clot in the popliteal vein
De Sanctis (2001) [
63 ] RCT Essaven gel (n = 10) Analogue symptomatic score
(range, 1–30, based on 3 points
[local pain, disability, swelling]
measured on a scale of 0 [normal]
to 10 [unbearable]); skin
temperature
Average score and average skin
temperature were signi fi cantly lower at
4 weeks with Essaven gel ( P < .05)
Placebo (n = 10)
Control (n = 10)
All patients received enoxaparin
(0.1 mL/10 kg) and elastic
compression for treatment period
(4 weeks)
(continued)
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148
J.A. Caprini and M.J. Verta
Study Design Interventions Measured outcomes Results
Belcaro (1999) [
29 ] RCT ES alone (n = 78) DVT or SVT extension at 3 or
6 months by DUS (patients with
DVT at 3 months were treated with
anticoagulation for 6 months)
DVT at 3 months:
ES + simple fl ush ligation (n = 78) ES = 7.6%
ES + stripping and perforating
veins, section, and tying (n = 70)
ES + ligation = 2.5%
ES + UFH (n = 71) ES + stripping = 2.8%
ES + LMWH (n = 76) ES + UFH = 0
ES + coumadin (n = 71) ES + LMWH = 0
ES + coumadin = 0
SVT extension at 3 months:
ES = 41%
ES + ligation = 14.1%
ES + stripping = 0
ES + UFH = 5.6%
ES + LMWH = 5.2%
ES + coumadin = 7%
SVT extension at 6 months:
ES = 16.7%
ES + ligation = 7.7%
ES + stripping = 1.4%
ES + UFH = 2.8%
ES + LMWH = 1.3%
ES + coumadin = 7%
No DVT was found at 6 months
Hanson (1998) [
15 ] Open (N = 17) Anticoagulation in patients with
SFJ thrombophlebitis or concomi-
tant DVT
Thrombus progression by DUS 7.6% improved
NSAIDs in patients with isolated
SVT
46.2% worse
46.2% unchanged
Ascher (1995) [
33 ] Open trial in patients with
sapheno-femoral junction
thrombosis
UFH + coumadin (n = 14) DVT or SVT extension by DUS or
symptomatic PE at 14 months
36% complete resolution
50% partial resolution
7% no resolution
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14915 Super fi cial Vein Thrombosis
Study Design Interventions Measured outcomes Results
Titon (1994) [
30 ] Randomized, open Nadroparin 6150 anti-Xa IU
(n = 31)
SVT signs and symptoms at
8 weeks
Signi fi cantly greater improvement in
signs and symptoms with nadroparin
vs naproxen ( P = .007)
Nadroparin 31.5 anti-Xa IU/kg
(n = 40)
Naproxen (n = 39)
Agus (1993) [
64 ] RCT Nimesulide (n = 30) SVT signs and symptoms (pain,
redness, swelling) at 20 days
Ef fi cacy rating:
Diclofenac (n = 30) Nimesulide = 87% excellent, 13% good
Diclofenac = 93% excellent, 3% good,
treatment fair in one patient
No signi fi cant differences in any
parameters
No adverse events
Lohr (1992) [
40 ] Retrospective chart review of
patients with SVT extending to
the SFJ
Surgery (n = 41) VTE and/or SVT recurrence at
4 months
7.3%, including one patient with DVT
and PE
Adverse events included wound
cellulitis and one wound hematoma
Plate (1985) [
41 ] Open Surgery (n = 28) VTE 14.3%
Husni (1982) [
9 ] Open NSAIDs (n = 60) PE 17% with NSAIDs, including one fatal
PE
Anticoagulation (n = 22) 0% with anticoagulation
Surgery (ligation and stripping,
n = 135)
0% with surgery
Lofgren (1981) [
21 ] Open Surgery (excision of thrombosed
segments and stripping, n = 163)
VTE or SVT recurrence at average
of 5 years
PE = 1.2%
SVT recurrence = 4.3%
Williams (1964) [
65 ] Open Surgery (n = 92) VTE 0
Hafner (1964) [
26 ] Open Surgery (n = 133) VTE Surgery: 2.3% PE, 10.5% DVT
Medical (n = 191) Medical: 0
Gjores (1962) [
42 ] Open Surgery (n = 40) VTE 8% PE
RCT randomized controlled trial, VTE venous thromboembolism, SVT super fi cial venous thrombosis, DUS duplex ultrasound, NSAID nonsteroidal antiin fl ammatory drug, DVT
deep vein thrombosis, PE pulmonary embolism, UFH unfractionated heparin, aPTT activated partial thromboplastin time, IU international units, ES endovascular sclerotherapy,
SFJ saphenofemoral junction
*vs placebo
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150
J.A. Caprini and M.J. Verta
Anticoagulation is mandatory in patients
with SVT when DVT is present. Anticoagulation
is also often used when a thrombus is found in
the SPJ or SFJ or extends as free fl oating in the
CFV or popliteal veins. SVT involvement in the
thigh or near the SSV junction may behave sim-
ilar to a DVT, can result in PE. and propagation
into the deep venous system is common. If the
thrombus is adherent or located noncontigu-
ously, anticoagulation is mandatory [
7 ] . Since
the increasing recognition of the risk of con-
comitant VTE with SVT, anticoagulation has
been proposed as a feasible treatment for all
patients with SVT.
Anticoagulants that have been evaluated in
patients with SVT include unfractionated hepa-
rin (UFH) [ 29, 32, 33 ] , coumadin [ 29, 33, 34 ] ,
and low-molecular-weight heparins (LMWH)
(Table 15.2 ) [ 4, 29, 30, 35 ] . Based on the limited
available data, LMWH appears to be the most
effective treatment for SVT (Table 15.2 ) [ 29, 30,
36 ] . A newer class of anticoagulants, factor Xa
inhibitors, has also been studied in SVT and in
studies of prevention of VTE in orthopedic sur-
gery, the factor Xa inhibitor fondaparinux showed
a bene fi t in risk reduction of VTE over LMWH
and had a similar safety pro fi le [ 37 ] . A large
(N = 3,000), European, randomized, placebo-
controlled study of fondaparinux with standard
symptomatic treatment vs standard symptomatic
treatment alone in symptomatic isolated SVT
with a primary endpoint of VTE (including DVT,
PE, and SVT recurrence or extension) and death
has been completed [ 3 ] . In the study, involving
more than 3,000 patients in 17 European coun-
tries, 1.2% of patients in the placebo group expe-
rienced deep vein thrombosis and 0.3% suffered
pulmonary embolism.
In all, 5.9% of the placebo group experienced
one or more of the complications that made up
the composite primary outcome measure of the
study, which also included SVT recurrence or
extension in addition to pulmonary embolism
and deep vein thrombosis. None of the 1,500
patients assigned to daily injections of 2.5 mg of
fondaparinux had pulmonary embolism ( P = 0.03
versus placebo) and 0.2% experienced deep vein
thrombosis ( P < 0.001). Recurrent and extended
SVT both occurred in 0.3% of the fondaparinux
group ( P < 0.001 versus placebo for both). The
primary composite endpoint occurred in 0.9%
of patients taking fondaparinux ( P < 0.001).
Treatment lasted 45 days and patients were fol-
lowed for an additional month. Ef fi cacy was
maintained through day 77, and Decousus
reported that bleeding events were no more com-
mon with fondaparinux than with placebo, both
overall and within categories of major, fatal,
clinically relevant, and minor bleeds. Although
this study showed the ef fi cacy of a prophylactic
dose of fondaparinux the short follow-up may
not re fl ect the true nature history of this disease.
Decousus in a subsequent publication studied
844 patients with SVT and 210/844 individuals
(24.9%) also had DVT or symptomatic pulmo-
nary emboli on admission to the study [ 3 ] . The
remaining 600 patients with SVT only were fol-
lowed for 3 months and 58 (10.2%) developed
thromboembolic complications. These events
included DVT, PE, extension of SVT or new
SVT. These events occurred despite the fact that
544 patients (90.5%) received anticoagulants.
Unfortunately these anticoagulants were admin-
istered for a mean period of 11 days although
69.4% received therapeutic doses of LMWH. In
our experience this is a grossly inadequate time
frame for treatment.
Surgery, including thrombectomy, vein strip-
ping, vein ligation, and sclerotherapy, has also
been suggested for treatment of SVT [ 7, 9, 26,
29, 35, 39– 42 ] . Surgery may be as effective as
anticoagulation when a thrombus is found in the
SPJ or SFJ and extends as free fl oating in the
CFV or popliteal veins [
7 ] . Disadvantages of sur-
gery are that it is invasive and there is a risk of PE
when performed early [
43 ] . Stripping and sclero-
therapy can increase the risk of PE [
44, 45 ] , with
symptomatic PE reported in up to 8% of patients
following stripping [
42 ] . In addition, in a recent
study where surgery and LMWH were compared,
the incidence of PE was 6.7% with surgery and
0% with LMWH ( P = ns). Thus, postoperative
prophylactic anticoagulation should be used
to prevent thrombotic complications following
surgery [
12 ] . Although it has been suggested that
stripping can eradicate varicose veins and, thus,
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15115 Super fi cial Vein Thrombosis
the cause of SVT [ 6 ] , it has been reported that
ligation alone or combined with sclerotherapy is
associated with an incidence of 50% or more of
recurrent veins [
46– 49 ] .
Clinical Data
Most of the studies published in patients with
SVT were not well designed and many studies
did not report the incidences of VTE, SVT pro-
gression, or adverse events (Table 15.2 ). There
are only several published randomized, controlled
studies in this patient population. A pivotal ran-
domized, controlled trial was the STENOX trial
[ 4 ] . This trial was a relatively large (N = 427),
randomized, double-blind trial that compared
two doses of the LMWH enoxaparin (40 mg and
1.5 mg/kg) with elastic compression stockings,
the NSAID tenoxicam with elastic compression,
and elastic compression stockings alone in
patients with SVT [ 4 ] . Treatment duration was
8–12 days. The primary outcome was ultrasono-
graphically proven DVT or symptomatic PE at
day 12 and the secondary endpoint was recurrent
SVT or thrombus extension toward the SFJ. The
incidence of DVT was reduced compared with
placebo in all treatment groups, with the lowest
incidence in patients treated with enoxaparin.
DVT incidence at day 12 was 3.6% with placebo,
0.9% with 40 mg enoxaparin ( P = .37 vs placebo),
1.0% with 1.5 mg/kg enoxaparin ( P = .37 vs
placebo), and 2.1% tenoxicam ( P = .69 vs placebo).
The incidence of the combined endpoint of DVT
and SVT recurrence or extension was signi fi cantly
reduced compared with placebo in all treatment
groups (Fig. 15.1 ). No death or major hemor-
rhage occurred during the study. Although this
study was not suf fi ciently powered to detect a
signi fi cant difference between enoxaparin and
tenoxicam, the incidence of the combined end-
point with NSAIDs was approximately double
that with the 1.5 mg/kg dose of enoxaparin
(Fig. 15.1 ), suggesting that LMWH is more effec-
tive than NSAIDs in SVT [ 36 ] .
Belcaro and colleagues conducted another
relatively large (N = 526), randomized, controlled
study that compared compression alone, early
surgery (simple fl ush ligation or fl ush ligation
and perforating veins ligation and stripping),
low-dose UFH with delayed surgery, LMWH
with delayed surgery, and oral anticoagulation
(all with compression stockings) [ 29 ] . In this
study, there was no signi fi cant difference among
treatment groups in the incidence of DVT at
3 months (Fig. 15.2 ). SVT extension was
signi fi cantly higher in the compression only
(16.7% at 6 months) and saphenous ligation
groups (7.7% at 6 months; P < .05). Stripping was
associated with the lowest incidence of thrombus
extension (1.4% at 6 months). Although this
study was not suf fi ciently powered to detect
signi fi cant differences among the anticoagulants
evaluated, it appears that LMWH is associated
with a lower incidence of SVT extension com-
pared with UFH and coumadin [
36 ] .
35
30.6
8.3
∗
6.9
∗
14.9
30
25
20
15
10
5
0
Place bo
Percent of patients with DVT or
SVT recurrence or extension
Enoxaparin 40
mg
Enoxaparin
1.5 mg/kg
Tenoxicam
Fig. 15.1 Percent of patients with DVT and/or
SVT recurrence or extension at day 12 [
4 ] .
* P < 0.001 vs placebo,
†
P < 0.01 vs placebo. DVT
deep vein thrombosis, SVT super fi cial venous
thrombosis
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152
J.A. Caprini and M.J. Verta
Two other key randomized, controlled studies
evaluated the ef fi cacy of high and low doses of
anticoagulants in SVT. Marchiori and colleagues
conducted a randomized, controlled study
(N = 60) that compared high and low-dose subcu-
taneous UFH (12,500 IU for 1 week, 10,000 for
3 weeks vs 5,000 IU for 4 weeks) [ 32 ] . Endpoints
were asymptomatic involvement of the deep
venous system (by serial ultrasound) at 3 months
and/or symptomatic venous thromboembolic
events at 6 months. At 6 months, there were
signi fi cantly fewer overall VTE events with high-
dose UFH (20% vs 3.3% P = .05). There were no
cases of major bleeding during treatment.
Prandoni and colleagues conducted a random-
ized, controlled study (N = 164) that compared a
fi xed prophylactic dose (2850 anti-Xa IU) with
body-weight-adjusted therapeutic doses of
nadroparin once daily for 1 month [
50 ] . The pri-
mary endpoint was asymptomatic and symptom-
atic SVT extension and/or VTE complications at
3 months. There was no signi fi cant difference
between groups in the primary endpoint (8.6%
with the prophylactic dose vs 7.2% with the ther-
apeutic dose, P = .74). No major bleeding was
observed in any patient.
Clinical Considerations
Screening for thrombophilia disorders is not rec-
ommended by many authorities for SVT. We
have a different view since we have discovered a
number of serious thrombophilic disorders in
patients with SVT as well as VTE regardless if
the incident was idiopathic or provoked [ 16 ] . We
perform the routine tests in Table
15.3 for all
patients with a past history of VTE, family his-
tory of VTE, and all those with acute VTE or
SVT. The optional tests are reserved for patients
with recurrent VTE and/or a family history of
VTE and normal routine tests. This practice is
based on 20 years of caring for these patients and
may not be for everyone. It is purely our standard
of practice. Our experience has suggested that
full-dose anticoagulation is necessary in these
45
40
35
30
25
20
15
10
5
0
Compression
Ligation
Stripping
LDUFH
LMWH
Coumadin
Percent of patients
DVT 3 months
EXT 3 months
EXT 6 months
Fig. 15.2 Percent of patients with new DVT at 3 months
and thrombus extension at 3 or 6 months [
29 ] . Patients
with DVT at 3 months were given anticoagulation for at
least 6 months. No new DVT was observed at 6 months.
DVT deep vein thrombosis, EXT thrombus extension,
LDUFH low-dose unfractionated heparin, LMWH low–
molecular-weight heparin
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15315 Super fi cial Vein Thrombosis
patients. The duration of anticoagulation in our
hands is determined by residual thrombotic
changes and until they have resolved we continue
anticoagulation. Once clearing of the venous seg-
ments has occurred, anticoagulation is stopped
and d -dimer assay done in 1 month. Those with
normal values can continue off anticoagulation
and be scheduled for ablation and/or surgical vein
procedures. In those with abnormal d -dimer val-
ues we suggest resuming anticoagulation for
another 6 months and repeating the d -dimer 1
month after stopping the anticoagulants.
Thrombophilia testing is done in all of these indi-
viduals in order to identify those with defects.
The presence of one marker usually would not
dictate any change in the above protocol unless a
severe defect is uncovered. These would include
homozygous Factor V Leiden or prothrombin
20210 gene mutation as well as a true protein C
or S de fi ciency. Those with antithrombin
de fi ciency or grossly elevated antiphospholipid
antibody titers or those with the Lupus anticoag-
ulant also may require ongoing anticoagulation.
Conclusions
There are two major treatment paradigms in
SVT: (1) NSAIDs and compression unless
there is proven DVT or symptoms of DVT; (2)
anticoagulation and compression in all patients
with SVT. NSAIDs are not effective in pre-
venting VTE in other patient populations and
it is recommended that they not be used for
this purpose [ 31 ] . Although there are limited
data on the treatment of SVT and de fi nitive
recommendations regarding optimal treatment
have not been made, a systematic meta-analy-
sis found that anticoagulation appears to be
most effective for preventing VTE and SVT
extension and/or recurrence [ 36 ] .
Based on the limited available data, LMWH
appears to be more effective than UFH in SVT
[ 36 ] . Some suggest that an intermediate dose
of LMWH for at least 1 month is reasonable
based on the available data [ 32, 36, 50 ] . The
factor Xa inhibitor fondaparinux has also been
studied and shown to be very effective in
patients with SVT and is an option for treat-
ment of SVT. Surgery may be a limited option
for patients with SVT, particularly in those
with a thrombus in the SPJ or SFJ and extends
as free- fl oating in the CFV or popliteal veins,
but it is invasive and is associated with increased
risk for PE. We recommend treating the SVT
as described in the clinical consideration sec-
tion and achieving thrombus resolution before
embarking on venous extirpation procedures.
Acknowledgements The authors would like to acknowl-
edge the editorial assistance of Holly Capasso-Harris,
Ph.D. in the preparation of this chapter.
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