Clinical Review & Education

JAMA | Review

Superficial Vein Thrombosis

A Review
Gregory Piazza, MD, MS; Darsiya Krishnathasan, MS; Nada Hamade, MPH; Francisco Ujueta, MD, MS;
Giovanni Scimeca, MD; Marcos D. Ortiz-Rios, MD; Bridget McGonagle, BS; Jean-Philippe Galanaud, MD, PhD;
David Jiménez, MD, PhD; Manuel Monreal, MD, PhD; John Fanikos, RPh, MBA; Anahita Dua, MD, MBA, MSc;
Leben Tefera, MD; Raghu Kolluri, MD; Sahil A. Parikh, MD; Walter Ageno, MD; Samuel Z. Goldhaber, MD;
Jeffrey I. Weitz, MD; Lisa K. Moores, MD; Isabelle Quéré, MD, PhD; Behnood Bikdeli, MD, MS

Multimedia
IMPORTANCE Superficial vein thrombosis (SuVT) is characterized by thrombus in the Supplemental content
superficial veins, typically in the lower or upper extremities, and has an estimated annual
incidence of 64 to 131 per 100 000 person-years. Approximately 10% of patients with SuVT CME at jamacmelookup.com

progress to deep vein thrombosis (DVT) or pulmonary embolism (PE).

OBSERVATIONS Endothelial injury (caused by infection or intravenous devices), venous

stasis (such as from chronic venous insufficiency or prolonged immobility), and
hypercoagulability (due to cancer or pregnancy) are pathophysiologic factors associated
with SuVT. Clinical risk factors for lower extremity SuVT are similar to those of DVT and PE
and include pregnancy, varicose veins, and active cancer. The incidence of SuVT is greater in
females than males (78-167 compared with 49-116 per 100 000 person-years). In contrast
with lower extremity SuVT, upper extremity SuVT is primarily caused by indwelling
intravenous catheters. Patients typically present with a tender, red, palpable cord under the
skin in the upper or lower extremity. D-dimer testing has a sensitivity of approximately 48%
to 74.3% and, therefore, is not reliable for excluding SuVT. Approximately 25% of patients
with lower extremity SuVT present with concomitant DVT, likely because risk factors for SuVT
and DVT are similar and because SuVT can extend into deep veins. In people without classic
symptoms and signs of SuVT, ultrasonography can establish the presence and extent of the
thrombus. Management may include elastic compression stockings and nonsteroidal
anti-inflammatory drugs. For patients with SuVTs that are at least 5 cm long or those with
persistent or worsening symptoms despite several days of conservative therapy, treatment
includes anticoagulation with fondaparinux 2.5 mg. Alternative anticoagulation treatment
includes rivaroxaban 10 mg once daily and low-molecular-weight heparins (eg, enoxaparin
40 mg once daily), which may reduce subsequent venous thromboembolic events. SuVT
located within 3 cm of a deep vein should be treated with therapeutic doses of
anticoagulation such as direct oral anticoagulants.

CONCLUSIONS AND RELEVANCE SuVT typically presents as a tender, painful, palpable cord
under the skin. Management may include elastic compression stockings, nonsteroidal
anti-inflammatory drugs, and systemic anticoagulation with fondaparinux 2.5 mg or
rivaroxaban 10 mg. SuVTs within 3 cm of a deep vein should be treated with therapeutic dose
anticoagulation.

Author Affiliations: Author

affiliations are listed at the end of this
article.
Corresponding Author: Behnood
Bikdeli, MD, MS, Division of
Cardiovascular Medicine, Brigham
and Women’s Hospital, 75 Francis St,
JAMA. doi:10.1001/jama.2025.15222 Boston, MA 02115 (bbikdeli@bwh.
Published online September 15, 2025. harvard.edu).

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 Clinical Review & Education Review Superficial Vein Thrombosis: A Review

S
uperficial vein thrombosis (SuVT), defined as a thrombus ment). For data regarding epidemiology and risk factors, larger pro-
within the superficial veins of the lower or upper extremi- spective studies were prioritized. For evidence regarding treat-
ties, has an estimated annual incidence of 64 to 131 ment, randomized clinical trials (RCTs) and meta-analyses based on
per 100 000 person-years.1,2 In comparison, the incidence of well-designed RCTs were prioritized. Additional articles were iden-
deep vein thrombosis (DVT) is 147 to 179 cases per 100 000 tified from the reference lists of articles identified during the
person-years.3,4 SuVT is most common in the great saphenous and search. Of 200 articles identified, 83 were included, consisting of
small saphenous veins of the lower extremities and the basilic and 14 RCTs, 7 meta-analyses, 32 longitudinal observational studies, 29
cephalic veins of the upper extremities (Figure 1).5 SuVT can also review articles, and 1 cross-sectional study.
manifest in the chest wall, breasts, or penis (Mondor disease).6 If
untreated, the 45-day incidence of DVT or pulmonary embolism
(PE) and extension of SuVT in patients with lower extremity SuVT
Discussion
can be as high as 1.3% and 3.4%, respectively.7 This review sum-
marizes current evidence regarding the diagnosis and treatment Pathophysiology
of SuVT. SuVT, which may occur due to venous stasis, endothelial injury,
and/or hypercoagulability, begins when a thrombus forms in a
superficial vein near the skin surface and partially or fully obstructs
blood flow (Figure 1 and Figure 2; eFigure 4 in the Supplement).8-10
Methods
Nearly 45% of lower extremity SuVTs occur in patients with vari-
A literature search of PubMed was conducted for English-language cose veins.11,12 Chronic venous insufficiency is observed in up to
articles using the search terms superficial vein thrombosis and half of patients with lower extremity SuVT and may result from
superficial thrombophlebitis. A search was conducted on Septem- venous obstruction and/or venous valvular incompetence.13,14
ber 1, 2023, for articles published between 1950 and 2023. A sec- Chronic venous thrombosis may obstruct venous return through
ond search was conducted on June 9, 2025, for articles published superficial veins. Venous valvular incompetence, failure of venous
between 2023 and 2025 (eTable 1 and eFigures 1-3 in the Supple- valves to function due to damaged venous valves or dilated veins,

Figure 1. Common Sites of Superficial Vein Thrombosis With a Brief Summary of the Pathophysiology

A Common sites of superficial vein thrombosis (SuVT) B Pathophysiology of SuVT

UPPER EXTREMITY SITES LOWER EXTREMITY SITES SuVT occurs when a thrombus forms in a vein near the skin surface
and obstructs blood flow, resulting in pain, swelling, redness, and
Deep veins are shown for context often a palpable cord-like vein under the skin.
but are not potential sites of SuVT. External iliac
Axillary vein (deep) vein (deep)
Upper extremity SuVT can result when an intravenous catheter
Common femoral damages the venous endothelium, initiating an inflammatory
Brachial vein (deep) vein (deep) response and thrombosis.

Cephalic vein Superficial femoral

Endothelial damage
vein (deep) Thrombus
initiates thrombosis
Basilic vein
Great saphenous vein
(72.9% of lower Inflammation
extremity SuVT cases)
Intravenous
Accessory cephalic vein catheter Impeded
Perforator vein blood flow
Median cubital vein

Median antebrachial vein Popliteal vein (deep)

Cephalic vein
(57% of upper
extremity SuVT cases)
Lower extremity SuVT can result when insufficient blood flow
Basilic vein (such as due to vessel dilation), damaged venous valves, and inability
Anterior tibial vein (deep)
(14% of upper of calf muscles to pump blood efficiently initiates blood clotting.
extremity SuVT cases) Small saphenous vein,
posterior surface of leg Damaged
(25.7% of lower valve
extremity SuVT cases)

Great saphenous vein

Reverse Inflammation
blood flow

Small saphenous vein

Static blood Thrombus
SuVT can also occur in veins in the chest begins to
wall, breasts, and penis. Dorsal pedal venous arch thrombose
Perforator veins that connect superficial Impeded
to deep veins in the lower extremity may Vein dilation blood flow
be at risk for venous thrombosis.

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 Superficial Vein Thrombosis: A Review Review Clinical Review & Education

Figure 2. Flow Diagram Summarizing Approach to Diagnosis and Management of Superficial Vein Thrombosis

Patient presents with signs and symptoms of superficial vein thrombosis (SuVT)
Pain, erythema, swelling, and/or presence of tender palpable cord

Clinical presentation
Physical examination of extremity Risk factor assessment
to assess extent of symptoms Personal history of SuVT Pertinent clinical risk factors (active cancer, history of venous Thrombophilia (eg, seropositivity
thromboembolism [VTE], aged >65 y, use of estrogen-containing for antiphospholipid antibodies,
products or pregnancy, and acute immobility) Leiden V genetic variant)

Potential diagnosis of SuVT

Diagnosis
Duplex ultrasonographya of superficial and deep veins (can establish the diagnosis and demonstrate location and length of thrombus)
Duplex ultrasonography may not be necessary in patients with characteristic symptoms and signs of SuVT
who have a low likelihood of an alternative diagnosis or thrombus progression

SuVT present Deep vein thrombosis (DVT) present Treat as a DVT

Management of SuVT
LOWER EXTREMITY SuVT UPPER EXTREMITY SuVT
If an intravenous catheter is involved,
remove as soon as possible.
Thrombus is <3 cm from saphenofemoral
venous junction Thrombus is <3 cm from deep veins

NO YES
Treat as a DVT: therapeutic dose of anticoagulation YES NO
for a minimum of 3-6 mo

Thrombus is >5 cm in length Thrombus is >5 cm in length

Fondaparinux 2.5 mg/d for 45 d, then reassess
NO YES YES NO
Alternative treatments: rivaroxaban 10 mg/d or low-
molecular-weight heparin (eg, enoxaparin 40 mg/d)

Conservative therapy (eg, warm compresses, compression therapy with elastic

compression stockings, NSAIDs, topical creams containing NSAIDs, limb elevation)

If there are multiple risk factors (eg, prior VTE, known thrombophilia, active cancer),
consider low-intensity anticoagulation (eg, fondaparinux 2.5 mg/d)

Symptoms are persistent or worsening after 72 h

NO YES

Continue conservative treatment Fondaparinux 2.5 mg/d (rivaroxaban 10 mg/d

or enoxaparin 40 mg/d as alternatives)

NSAID indicates nonsteroidal anti-inflammatory drug. presumed sensitivity and specificity. However, in cases with typical symptoms
a
Ultrasonography is considered the reference standard for evaluating and and a low likelihood of alternative diagnoses, thrombus progression, or deep
determining thrombus extension due to its accessibility, high resolution, and venous involvement, confirmatory imaging might not be required.

and the inability of calf muscles to pump blood effectively may also associated with SuVT.17,24,25 Inherited or acquired thrombophilia
contribute to venous hypertension.14,15 (eg, seropositivity for antiphospholipid antibodies) may also be as-
sociated with increased risk of SuVT.26,27
Risk Factors for SuVT The presence of impaired venous blood return, use of oral
Risk factors associated with SuVT include varicose veins, preg- contraceptives or hormone replacement therapy with estrogen or
nancy, cancer, and the presence of an upper extremity catheter.16 progesterone, immobility, and venous varicosities can contribute
Other risk factors and comorbidities associated with SuVT include to the pathogenesis of SuVT.1,7 Pregnancy is associated with in-
trauma, recent surgery, acute infection or active inflammation, his- creased rates of SuVT, likely related to compression of pelvic veins
tory of venous thromboembolism (VTE), and age 60 years or older by the uterus, decreased mobility, increased estrogen and coagu-
(Table 1; eTable 2 in the Supplement).1,7,16,18-23 Approximately 6.1% lation factors (eg, factors II, VII, VIII, IX, and XII), decreased protein
to 16.6% of people diagnosed with SuVT have active cancer. Colo- S levels, and inhibition of fibrinolysis.28-31 Risk of SuVT is highest dur-
rectal, breast, and urinary cancers are the most common cancer types ing the postpartum period (12 weeks postpartum) compared with

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 Clinical Review & Education Review Superficial Vein Thrombosis: A Review

40.7 hours.20 The risk of SuVT does not significantly differ with the
Table 1. Summary of Common Risk Factors Associated With SuVT
use of more malleable silicone-based catheters compared with
Relationship to superficial
Risk factor venous thrombosis Comments
polyurethane-based catheters.36,37 In a retrospective study of 328
Varicose veins In a case-control study, Varicose veins are a common patients with upper extremity SuVT provoked by intravenous cath-
patients with SuVT were more risk factor for lower eters, the most common underlying predisposing conditions were
likely to have varicose veins extremity SuVT. Their
than patients without (43.7% association with upper hematologic malignancies (29.6%), solid cancers (11.3%), infec-
vs 5.3%; aOR, 12.1 [95% CI, extremity SuVT has not been tions or inflammatory conditions (35.1%), and hepatogastrointes-
5.2-28.2]).16 investigated.
tinal disorders (25.3%).38
Malignancy Cancer is a common While the thrombogenicity
comorbidity in patients with of cancer is well-known for
SuVT. Some,17 but not all,18 deep vein thrombosis and Epidemiology
studies suggest a higher risk pulmonary embolism, there
of future cancer diagnosis in are currently no matched The incidence of SuVT ranges from 64 to 131 per 100 000 person-
those with SuVT. cohort or case-control years (eTable 3 in the Supplement). A primary care–based prospec-
studies investigating
malignancy as a risk factor tive study from France conducted between 2011 and 2012 by the
for lower or upper extremity
SuVT.
Superficial Thromboembolism Prevalence High-risk (STEPH) group
Obesity In a case-control study, Although known as a risk (n = 265 687) reported an incidence of 64 cases of lower extrem-
patients with SuVT were more factor for lower extremity ity ultrasonography-confirmed SuVT per 100 000 person-years
likely to have obesity (BMI SuVT, its association with
>30)2 than patients without upper extremity SuVT is not (95% CI, 55-74).1 A retrospective cohort study that included all pa-
(36.4% vs 18.5%; aOR, 2.7 known. tients in the Utrecht General Practitioner Network in the Netherlands
[95% CI, 1.4-5.1]).16
(n = 1 534 845) conducted from 2010-2016 reported an incidence
Recent In a case-control study, Prospective data on past
immobilization patients with SuVT were more surgery/recent of 131 cases of lower extremity SuVT per 100 000 person-years
likely to have recent immobilization are limited (95% CI, 125-137).2
immobilization due to major for patients with upper
surgery or disease within 30 d extremity SuVT. SuVT is more common in females (incidence of 78 to 167
than patients without SuVT per 100 000 person-years) than males (incidence of 49 to 116 per
(14.6% vs 1.3%; aOR, 22.3
[95% CI, 4.8-103.9]).16 100 000 person-years),1,2 which may be due to a higher preva-
Pregnancy In a retrospective cohort Risk of SuVT is higher during lence of varicose veins in females. Approximately 50.5% of fe-
study, the incidence of SuVT the 12-week postpartum
during the antepartum and period compared with the males older than 18 years have varicose veins, compared with 30.1%
postpartum period was 0.6 antepartum period. Although in males older than 18 years.39 Pregnancy and the use of estrogen-
(95% CI, 0.5-0.6) per 1000 the risk of VTE during
person-years.19 pregnancy is well containing hormonal contraceptives may also be associated with an
established, no matched increased incidence of SuVT among females.40
cohort or case-control
studies have evaluated The most common sites of lower extremity SuVT are the great
pregnancy as a risk factor for saphenous vein (72.9%) and small saphenous vein (25.7%)
SuVT of the lower or upper
extremities. (Figure 1). SuVT located in the great saphenous vein can be identi-
Indwelling In a prospective study of 645 Indwelling catheters are the fied along the entire length of the vein, which runs from the medial
catheters patients receiving indwelling most common risk factors side of the foot up along the medial aspect of the lower leg and
catheters, SuVT was seen in for upper extremity SuVT;
51.9% of patients, with a however, more recent extends through the medial thigh, continuing to the inguinal region
mean placement time of prospective studies are
40.7 h.20 needed to determine the
(where the vein drains into the deep venous system near the
quantified magnitude of risk, groin). However, SuVT originating from tributaries, which are veins
stratified by catheter
diameter. that drain into the saphenous veins, especially those that connect
the superficial and deep vein systems (perforator veins), may be at
Abbreviations: aOR, adjusted odds ratio; BMI, body mass index (calculated as
weight in kilograms divided by height in meters squared); SuVT, superficial vein an increased risk of DVT (Figure 1).41-43 Bilateral SuVT is present in
thrombosis. 5% to 10% of patients with SuVT and is associated with prothrom-
botic states such as cancer or autoimmune diseases.43,44 There is a
paucity of data on the prevalence of SuVT across different racial
the antepartum period, with an incidence of 1.6 vs 0.3 per 1000 per- and ethnic groups.
son-years, respectively.19
Approximately 16% to 36% of people with SuVT have obesity Clinical Presentation
(body mass index >30). Approximately 40% of individuals with Typical presenting symptoms of SuVT may include erythema, local-
thromboangiitis obliterans, a small- and medium-sized vessel vas- ized pain, swelling, pruritus, hyperpigmentation, and a tender pal-
culitis associated with smoking, develop SuVT in their lifetime.32,33 pable cord. Physical findings may show induration of the surround-
Indwelling catheters are the primary cause of upper extremity ing tissue.38,45 In a retrospective study of 316 patients with lower
SuVT. Large-bore catheters, specifically 14-gauge catheters that have extremity SuVT, 76.9% had localized pain in a superficial vein, 60.1%
not been changed from one site to another for more than 72 hours, had a palpable cord, and 58.2% had erythema.46 Patients with up-
are associated with a particularly high risk of SuVT.34,35 In a prospec- per extremity SuVT may develop these symptoms along a cannu-
tive study of 645 patients conducted over 4 months, thrombophle- lated vein.47 However, in a study of 120 patients with cancer receiv-
bitis occurred in 40.9% of 330 patients receiving polyurethane- ing chemotherapy who had ultrasonography performed after
based cannulas and 63.5% of 315 patients receiving Teflon-based peripheral catheter insertion at 1 and 3 months or if symptomatic,
cannulas.20 Although intravenous catheter dwell time in each group 31 (26%) developed an upper extremity SuVT over 3 months, but
was not available, the overall mean intravenous catheter time was only 7 were symptomatic.48

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 Superficial Vein Thrombosis: A Review Review Clinical Review & Education

Table 2. Summary of Findings for Treatment of Superficial Vein Thrombosis

Adverse events associated with the
Intervention Summary of findings in clinical trials therapy Comments
Fondaparinux 2.5 mg for Significantly reduced SuVT progression, PE, Major bleeding occurred in 1 patient Evidence is based on 1 large clinical trial.
45 d DVT, and recurrence. In a large RCT, with 3002 (0.1%) in each group (P > .99).
patients with lower extremity SuVT, treatment
with fondaparinux 2.5 mg vs placebo for 45 d
demonstrated efficacy over placebo with an
absolute risk reduction of 5% (RR, 0.15
[95% CI, 0.08-0.26]).7
Rivaroxaban 10 mg Noninferior to fondaparinux for prevention of No major bleeding events were reported Oral agent offers convenience
symptomatic events. In an RCT of 472 patients in either group. Clinically relevant advantage. The noninferiority margin
with isolated lower extremity SuVT, the nonmajor bleeding was reported in 6 of was relatively wide (4.5%
primary outcomes occurred in 3.3% (7/211) 236 patients (3%) in the rivaroxaban absolute/relative difference) and does
of patients receiving rivaroxaban and 1.8% group and in 1 of 235 patients (<1%) in not exclude a smaller significant
(4/224) of patients receiving fondaparinux fondaparinux group. difference between fondaparinux and
(absolute difference, 1.53%; upper bound CI, rivaroxaban.
4.03%; P = .0025 for noninferiority).55
Low-molecular-weight In an RCT, patients with lower extremity SuVT One patient (0.9%) in the placebo group The trial was stopped prematurely due
heparin (varied doses)a were randomized to receive 2 different doses and 1 patient (0.9%) in the 1.5-mg/kg to slow recruitment. Several small
of enoxaparin, tenoxicam, or placebo. enoxaparin group had minor hemorrhage clinical trials assessed other LMWHs not
Treatment with enoxaparin 40 mg (−2.69 several weeks after discontinuation of available in the US.
[98.5% CI, −7.52 to 2.15]), enoxaparin 1.5 study medication.
mg/kg (−2.62 [98.5% CI, −7.53 to 2.28]), and
oral tenoxicam (not available in the US) 20 mg
(−1.47 [98.5% CI, −7.09 to 4.14]) did not
significantly reduce incidence of VTE/SuVT
compared with placebo.56
NSAIDs May be effective in reducing symptoms such Limited evidence of adverse events of Limited clinical trial evidence.
as pain and inflammation. Randomized trial NSAIDs from clinical trials.
data are limited to the tenoxicam group of the
clinical trial discussed above. 56
Compression stockings A single-center RCT involving 88 participants None reported There is currently only 1 RCT
evaluated the effect of daily subcutaneous investigating compression stocking for
40-mg enoxaparin and found that wearing treatment of SuVT compared with no
thigh-length compression stockings (23-32 compression stockings.
mm Hg) for 3 weeks, compared with no
compression stockings, did not significantly
reduce thrombus length (mean decrease of
12.8 cm vs 6 cm; P = .07) or SuVT-related
pain, as measured by the Lowenberg test
(mean reduction of 42.6 mm Hg vs 43 mm Hg;
P = .81).57
Surgical intervention There were 2 clinical trials investigating Ecchymosis and infection occurred in 2 Available data on surgical therapy are
saphenofemoral disconnection and superficial patients in the disconnection group limited. Therefore, surgical intervention
thrombectomy. The most recent study (6.7%) and none in the enoxaparin group. is note routinely recommended in the
included 60 patients evaluated the effect of Minor bleeding (epistaxis and rectal management of SuVT.
saphenofemoral disconnection vs LMWH. bleeding) occurred in 2 patients of the
Findings showed that there was no significant enoxaparin group (6.7%), and no
difference between the groups for recurrent bleeding events occurred in the
SuVT/VTE (10% in both groups). 58 disconnection group.
a
Abbreviations: DVT, deep vein thrombosis; NSAID, nonsteroidal Enoxaparin is the widely investigated low-molecular-weight heparin (LMWH).
anti-inflammatory drugs; PE, pulmonary embolism; RCT, randomized clinical
trial; RR, relative risk; VTE, venous thromboembolism.

Diagnostic Testing plex ultrasonography may not be necessary in patients with

Physical examination findings such as tender palpable cords asso- characteristic symptoms and signs of SuVT who have a low likeli-
ciated with erythema and pain are characteristic findings for SuVT.49 hood of an alternative diagnosis or thrombus progression, such as
However, confirmation of suspected SuVT with duplex ultrasonog- those presenting with a small area of induration, and without can-
raphy is often useful because other conditions, such as cellulitis, ery- cer or other major risk factors.
thema nodosum, phlebitis without thrombosis, DVT, lymphangitis,
insect bites, localized soft tissue infections, and hematomas, can pre- Treatment
sent with similar signs and symptoms to SuVT.50 SuVT treatment may include topical treatments for symptom re-
Although a D-dimer value greater than 500 ng/mL has 95% to lief, including heparin ointment or heparin spray gel, nonsteroidal
96% sensitivity for DVT and PE,51 its sensitivity is lower for SuVT, anti-inflammatory drugs (NSAIDs), and surgical procedures consist-
ranging from 48.0% to 74.3%.52,53 Therefore, D-dimer measure- ing of venous ablation or ligation. Systemic anticoagulation with
ment is not widely used for screening for or excluding SuVT.52,54 fondaparinux 2.5 mg daily or rivaroxaban 10 mg daily can reduce
No large diagnostic accuracy studies for consecutive and rep- thrombus progression and prevent future thrombotic events.7
resentative patients with signs or symptoms of SuVT exist. Duplex
ultrasonography is considered a reference-standard test for diag- Conservative Treatment
nosis and assessment of the extent of thrombus extension, be- Conservative therapy includes warm compresses, compression
cause it is accurate for evaluating superficial veins. However, Du- therapy with elastic compression stockings, NSAIDs, topical creams

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 Clinical Review & Education Review Superficial Vein Thrombosis: A Review

containing NSAIDs, and limb elevation (Table 2). Limb elevation and Superficial Thrombophlebitis Treated by Enoxaparin (STENOX) study
warm compresses have not been tested in high-quality RCTs.59 Com- group compared 4 treatments: enoxaparin 40 mg subcutaneously,
pression therapy, including elastic compression stockings, applies enoxaparin 1.5 mg/kg subcutaneously, oral tenoxicam 20 mg (a type
graduated pressure to the lower extremities with compression of NSAID), and placebo. All medications were administered once daily
strength highest at the ankles and decreasing proximally. This gradu- for 8 to 12 days in patients with isolated lower extremity SuVT mea-
ated compression promotes the return of venous blood flow, re- suring at least 5 cm.56 The primary outcome was incident DVT di-
duces venous stasis and venous hypertension, and may reduce agnosed by ultrasonography or symptomatic PE at 12-day follow-
thrombus propagation.60 A single-center RCT of 88 participants with up. The trial was stopped early due to slow recruitment after 427 of
SuVT who were treated with 40 mg of enoxaparin subcutaneously the planned 1260 individuals were randomized. The incidence of DVT
daily reported that, compared with a control group that did not re- was 0.9% in the 40-mg enoxaparin group, 1.0% in the 1.5-mg/kg
ceive compression stockings, thigh-length compression stockings enoxaparin group, 2.1% in the tenoxicam (not available in the US)
(23-32 mm Hg) for 3 weeks did not significantly reduce thrombus group, and 3.6% in the placebo group.56,63 There were no statisti-
length (decrease of 12.8 cm vs 6 cm; P = .07). Pain related to the SuVT cally significant differences in rates of DVT between therapy and pla-
was not significantly reduced (decrease of 42.6 mm Hg vs 43 mm cebo (enoxaparin 40 mg once daily: −2.69 [98.5% CI, −7.52 to 2.15];
Hg via the Lowenberg test by inflating a blood pressure cuff until pain enoxaparin 1.5 mg/kg once daily: −2.62 [98.5% CI, −7.53 to 2.28];
is felt; P = .81; 4.3 cm vs 3.5 cm via the visual analog scale; P = .33). and oral tenoxicam 20 mg once daily: −1.47 [98.5% CI, −7.09 to
However, this clinical trial may have lacked adequate statistical power 4.14]).56 No major bleeding events occurred.
to detect a smaller but meaningful treatment effect on thrombus In an RCT of 164 participants with SuVT of the greater saphe-
length.57 nous vein randomized to receive low-dose nadroparin (0.3 mL)
Topical over-the-counter treatments such as heparin ointment for 30 days or high-dose nadroparin (0.4 mL) for patients less than
or spray gel may relieve symptoms. Although heparin has anticoagu- 50 kg and +0.1 mL per additional 10 kg for patients above 50 kg
lant properties, when applied topically, it may reduce symptoms of for 10 days followed by half dose for 20 days, there was no signifi-
inflammation such as pain, redness, or tenderness.61,62 RCTs evalu- cant difference in the primary outcome of SuVT progression or VTE
ating topical treatments have been limited by small sample size, early at 3-month follow-up (8.6% vs 7.2%; absolute risk difference, 1.4
termination of the clinical trial, or absence of a placebo group.63 [95% CI, −6.9 to 9.7]).64
(eTable 4 in the Supplement). Although topical medications are the A noninferiority clinical trial randomized 472 patients with symp-
most common type of treatment evaluated in RCTs for upper extrem- tomatic SuVT greater than or equal to 5 cm above the knee and at
ity SuVT, the studies are typically low quality and limited by a small least 1 risk factor (eg, age >65 years, male sex, prior VTE, cancer, au-
sample size.47,63 Topical heparin requires a prescription and is avail- toimmune disease, non–varicose vein involvement) to receive riva-
able only at specialty compounding pharmacies in the US. There- roxaban 10 mg once daily or fondaparinux 2.5 mg once daily for 45
fore, NSAIDs such as naproxen or ibuprofen are typically used be- days. The primary efficacy outcome was a composite of sympto-
cause they are readily available over the counter and inexpensive. matic DVT or PE, progression or recurrence of SuVT, or all-cause mor-
tality. The noninferiority margin was defined as an absolute differ-
Anticoagulation ence in the primary outcome of 4.5%. At 45-day follow-up, the
Although multiple RCTs have evaluated the effects of anticoagula- primary outcome occurred in 3.3% (95% CI, 1.6%-6.7%) of pa-
tion for patients with SuVT, most had small sample sizes (Table 2). The tients in the rivaroxaban group (7 of 211) and 1.8% (95% CI, 0.7%-
most widely studied intervention for lower extremity SuVT is sys- 4.5%) of patients in the fondaparinux group (4 of 244), indicating
temic anticoagulation,63 although no high-quality RCTs have evalu- noninferiority of rivaroxaban compared with fondaparinux (abso-
ated anticoagulation for treating upper extremity SuVT. The Com- lute difference, 1.53%; 1-sided upper bound CI limit, 4.03%; P value
parison of Arixtra in Lower Limb Superficial Thrombophlebitis With for noninferiority = .003) at day 45.55 However, the chosen nonin-
Placebo (CALISTO) RCT assessed the efficacy of a 45-day course of feriority margin of 4.5% in this trial was a large absolute difference,
fondaparinux (2.5 mg subcutaneously once daily) vs placebo in 3002 and a smaller clinically meaningful difference in clinical outcomes was
patientswithlowerextremitySuVTatleast5cminlengthlocatedmore not excluded.65 Tenoxicam and nadroparin (LMWH) are not avail-
than 3 cm from the saphenofemoral junction.7 The primary efficacy able in the US.8,56,64,66
outcome was a composite of all-cause mortality, symptomatic VTE, NSAIDs may reduce discomfort in patients with SuVT, al-
symptomatic SuVT extension (toward the saphenofemoral junc- though high-quality RCTs are necessary.56 NSAIDs should be used
tion), or SuVT recurrence by day 47. The composite outcome oc- with caution in patients taking anticoagulants to decrease the risk
curred in 0.9% of participants in the fondaparinux group vs 5.9% of of gastrointestinal bleeding and other forms of bleeding.67
those in the placebo group (relative risk, 0.15 [95% CI, 0.08-0.26];
P < .001). The benefit of fondaparinux was primarily due to de- Surgical Intervention
creased SuVT recurrence and extension.7 Deaths occurred in 0.1% of After initiation of medical treatment, endovenous procedures, which
participants in each group.7 DVT or PE occurred in 3 patients (0.2%) close off or remove the lower extremity vein, may be considered to
treated with fondaparinux and 20 patients (1.3%) in the placebo group prevent SuVT recurrence, especially if venous reflux is identified on
(absolute risk difference, −1.1% [95% CI, −1.8% to −0.5%]). Rates of ultrasonography. Minimally invasive office-based treatments in-
bleeding were 1.0% in the fondaparinux group vs 0.9% in the pla- clude thermal ablation (radiofrequency or laser), in which an ultra-
cebo group.7 sonography-guided catheter is used to heat and close the vein, or
Low-molecular-weight heparin (LMWH) has been evaluated to sclerotherapy, in which liquid or foam is injected to collapse the af-
treat SuVT. A double-blind, double-dummy RCT conducted by the fected superficial vein. These procedures are typically performed by

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 Superficial Vein Thrombosis: A Review Review Clinical Review & Education

endovenous experts such as vascular surgeons, interventional ra- wise) for 30 days with 49 patients who received standard-dose
diologists, and interventional cardiologists.68 More invasive proce- tinzaparin of 131 IU/kg for 90 days. Ninety days of tinzaparin was
dures may be considered, such as surgical ligation of the great sa- associated with fewer recurrent VTE and SuVT events (0/147 vs 15/
phenous vein at the saphenofemoral junction or removal of the 147) (P = .004).75 However, the study was limited by its observa-
affected veins. An RCT of 60 patients with SuVT in veins proximal tional design and by the lack of uniform-dose standardization in the
to the knee compared saphenofemoral disconnection (ligating the 30-day treatment group, where some patients received only 75%
great saphenous vein and femoral vein) with enoxaparin (1 mg/kg of the full therapeutic dose.
twice daily for 1 day, then once daily for 21 days). Although the study People with SuVT are at increased risk of recurrent SuVT,
did not report a prespecified and a priori powered primary out- thrombus extension, and subsequent DVT and PE. The POST study
come, clinical outcomes, including SuVT recurrence, subsequent evaluated thromboembolic complications in 844 patients with
VTE, and treatment-related complications, were assessed. There symptomatic lower extremity SuVT of at least 5-cm length mea-
were 3 thrombotic events in both the disconnection group (1 SuVT sured by compression ultrasonography.43 Among 586 patients
recurrence and 2 nonfatal PE; 10%) and the enoxaparin group (60% of whom received anticoagulation) presenting with isolated
(3 SuVT recurrences; 10%).58 Complications of the surgical wound, lower extremity SuVT, at 3-month follow-up, 10.2% (95% CI, 7.7%-
more specifically ecchymosis and infection, occurred in 2 patients 12.7%) developed VTE (2.1% were asymptomatic and 8.3% were
in the disconnection group (6.7%) and none in the enoxaparin group. symptomatic).43 In patients with SuVT, residual reflux, consisting of
Minor bleeding (epistaxis and rectal bleeding) occurred in 2 pa- retrograde blood flow in the superficial vein, may exacerbate
tients (6.7%) in the enoxaparin group, and no bleeding events oc- venous insufficiency, which may lead to venous ulcers; however, to
curred in the disconnection group.58 our knowledge, rates of venous ulcers in patients with SuVT have
The risk of DVT for patients with SuVT after endovenous pro- not been reported.76
cedures such as ablation, sclerotherapy, or ligation/stripping is un- Characteristics associated with a worse prognosis in people with
clear. A prospective, observational study of 872 patients with SuVT SuVT include a history of cancer, history of VTE, absence of vari-
and no concomitant VTE found that those receiving invasive treat- cose veins, male sex, and SuVT involving the saphenofemoral pop-
ment within 12 months of the index event did not have a signifi- liteal junction. In an analysis of the multinational Registro Informa-
cantly higher risk of VTE at 3-month follow-up than those not un- tizado Enfermedad Tromboembolica (RIETE) registry, among 1140
dergoing invasive treatment (7.6% vs 8.1%).69 Despite these findings, patients with SuVT, those with cancer (n = 110) had higher 3-month
many studies lacked a comparator group, included only patients with odds of VTE (4.5% vs 1.9%; odds ratio [OR], 4.92 [95% CI, 1.82-
varicose veins, and had small sample sizes, making it difficult to as- 12.4]), major bleeding (2.7% vs 0.3%; OR, 9.56 [95% CI, 1.63-
sess the risk of DVT.63,70 After an endovenous procedure, enoxapa- 56.2]), and death (8.2% vs 0.3%; OR, 30.3 [95% CI, 8.41-141]) com-
rin 40 mg once daily or low-intensity direct oral anticoagulants for pared with those without cancer (n = 1030).77 In the POST study,
up to a week may be appropriate for patients at risk for VTE to pre- among the 586 patients presenting with isolated SuVT, male sex
vent postsurgery DVT.70 (35.5%; hazard ratio [HR], 2.63 [95% CI, 1.42-4.86]), history of
VTE (19.1%; HR, 2.18 [95% CI, 1.15-4.12]), and absence of varicose
Recommendations by Professional Societies veins (13.7%; HR, 2.06 [95% CI, 1.01-4.25]) were associated with an
As a result of limitations of existing evidence, recommendations from increased risk of thrombotic events at the 3-month follow-up.43 A
professional societies about the management of SuVT are largely pooled analysis of 2 registry studies that included 1178 patients re-
based on expert opinion rather than high-quality RCTs (eFigure 5 in ported that SuVT involving the saphenofemoral/popliteal junction
the Supplement). Professional societies advise treatment with (11%) was associated with an increased risk of VTE occurrence at 3
fondaparinux subcutaneously 2.5 mg once daily for 45 days in pa- months compared with patients without involvement of the junc-
tients with a lower extremity SuVT that meets the following criteria: tion (HR, 3.23 [95% CI, 1.25-8.33]).78 In a meta-analysis of 8 stud-
thrombus greater than or equal to 5 cm in length and greater than 3 ies that included 5998 patients, 448 with malignancy and SuVT,
cm away from the deep vein junction (eg, saphenofemoral junction) those with cancer-associated isolated SuVT had an increased rate
based on findings from the CALISTO trial.70-73 Rivaroxaban 10 mg once of VTE compared with patients without active malignancy (risk ra-
daily and low-dose LMWH (no specified type) have been recom- tio, 2.57 [95% CI, 1.78-3.71]; P < .001).79
mended as alternatives to fondaparinux, but high-quality evidence re- Patients with SuVT may present with concomitant DVT or PE.
garding these therapies is lacking, particularly for LMWHs.70-73 The Optimisation de l’Interrogatoire dans l’Évaluation du Risque
Thrombo-Embolique Veineux (OPTIMEV) study, a prospective reg-
Prognosis istry that included both inpatients and outpatients with ultrasonog-
Thrombotic complications from SuVT, such as the extension of SuVT raphy confirmed SuVT, reported that 22.3% of patients with SuVT
or progression to DVT, are higher in people who do not receive an- had concomitant DVT alone, 6.3% had both DVT and PE, and 0.6%
ticoagulation compared with those who receive anticoagulation.74 presented with PE only. Three-month mortality was significantly
Thromboembolic events such as DVT and PE can occur in up to 7% higher in patients presenting with concomitant DVT vs those with-
of patients with SuVT within 90 days after diagnosis, but whether out DVT (9.3% vs 1.2%; P < .001).24 A study from RIETE reported
anticoagulation therapy prevents these thrombotic events for du- an increased risk of subsequent PE in patients presenting with con-
rations longer than 45 days has not been studied in high-quality comitant lower limb SuVT and DVT (1.7%) compared with isolated
RCTs.7,55 A prospective observational study compared rates of VTE DVT (0.9%) at a median follow-up of approximately 6 months (rate
and SuVT recurrence at 120 days in 98 patients who received vari- ratio, 2.12 [95% CI, 1.13-3.75]).80 There are no high-quality data on
able-dose tinzaparin (175 IU/kg for extensive SuVT; 131 IU/kg other- the subsequent risk of PE in patients with upper extremity SuVT.

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 Clinical Review & Education Review Superficial Vein Thrombosis: A Review

SuVT should be advised to seek medical care if symptoms do not im-

Box. Commonly Asked Questions About Superficial prove within 7 days or in the case of worsening, including swelling
Vein Thrombosis (SuVT) or redness, which could indicate thrombus progression to DVT. Sys-
temic anticoagulation for 45 days is typically considered for pa-
What is the typical clinical presentation of SuVT?
tients with SuVT greater than 5 cm in length or those with worsen-
SuVT typically presents as a palpable, tender cord along the
ing or persistent symptoms despite conservative therapy. As detailed
superficial veins. In the lower extremities, it is frequently
associated with varicose veins, while in the upper extremities, it above, fondaparinux 2.5 mg once daily is the best studied and first-
most often occurs in patients with intravascular devices such as line treatment, with rivaroxaban 10 mg once daily and enoxaparin
intravenous catheters. 40 mg once daily being treatment alternatives. If the SuVT is closer
How is SuVT typically diagnosed? than 3 cm to the deep vein junctions, therapeutic anticoagulation
A suggestive history (such as known varicose veins or recent with regimens similar to those used for management of DVT should
placement of intravenous catheters and presence of risk factors be considered, such as therapeutic doses of direct oral
such as prior venous thrombosis or pregnancy), physical anticoagulants81 (Box). Follow-up ultrasonography should be per-
examination findings of tender palpable cords associated with formed within 1 week for patients with worsening symptoms, such
erythema and pain are often sufficient to diagnose SuVT. In
as visible extension of the SuVT proximally or more diffuse extrem-
patients with suspected SuVT or those with concern for proximal
extension of the thrombus, ultrasonography can establish the
ity edema. New-onset dyspnea or chest pain in patients with SuVT
diagnosis and assess the extent of thrombus propagation. should prompt evaluation for PE, typically with computed tomo-
graphic pulmonary angiography.
Does treatment of SuVT require anticoagulation?
Anticoagulation is recommended for thrombus >5 cm in length,
thrombi that do not improve with conservative measures. Limitations
First-line anticoagulation therapy for SuVT is fondaparinux 2.5 mg This review has several limitations. First, the quality of included stud-
daily or rivaroxaban 10 mg daily for 45 d. Anticoagulation is also ies was not formally assessed. Second, relevant studies may have
recommended for SuVT within 3 cm of a deep vein junction and been missed. Third, only SuVT in the upper and lower extremities
should be treated similarly to deep vein thrombosis with was reviewed. Fourth, few clinical trials have been performed to in-
full-intensity anticoagulation.
form the treatment of SuVT. Fifth, some studies were not specific
in distinguishing between isolated phlebitis (inflammation of the ves-
Practical Considerations sel wall) vs thrombophlebitis or SuVT.
The diagnosis of SuVT can often be made clinically in the context of
a suggestive history and physical examination. For patients in whom
there is uncertainty about the diagnosis or extent of thrombi, ultra-
Conclusions
sonography should be considered (Figure 2).12,43,80 Treatment with
NSAIDs for acute SuVT is appropriate for treating pain. Patients may SuVT typically presents as a tender, painful, palpable cord under the
be treated with anticoagulation if they have greater symptom se- skin. Management may include elastic compression stockings,
verity, thrombus size greater than 5 cm, proximity to the deep veins NSAIDs, and systemic anticoagulation with fondaparinux 2.5 mg
(ie, within 3 cm of the deep vein), and presence of underlying risk or rivaroxaban 10 mg. SuVTs within 3 cm of a deep vein should be
factors for propagation to the deep veins, such as male sex, cancer, treated with therapeutic doses of anticoagulation such as direct
and history of VTE.12,43,80 Patients treated with topical agents for oral anticoagulants.

ARTICLE INFORMATION (Jiménez); Chair for the Study of Thromboembolic Montpellier, France (Quéré); Center for Outcomes
Accepted for Publication: August 7, 2025. Disease, Faculty of Health Sciences, UCAM, Research and Evaluation, Yale New Haven Hospital,
Universidad Católica San Antonio de Murcia, New Haven, Connecticut (Bikdeli).
Published Online: September 15, 2025. Murcia, Spain (Monreal); CIBER Enfermedades
doi:10.1001/jama.2025.15222 Author Contributions: Drs Piazza and Ms
Respiratorias (CIBERES), Madrid, Spain (Monreal); Krishnathasan served as co–first authors and
Author Affiliations: Division of Cardiovascular North American Thrombosis Forum, Brookline, contributed equally to the work.
Medicine, Brigham and Women’s Hospital, Harvard Massachusetts (Fanikos); Division of Vascular
Medical School, Boston, Massachusetts (Piazza, Surgery, Department of Surgery, Massachusetts Conflict of Interest Disclosures: Dr Piazza
Krishnathasan, Hamade, Ujueta, McGonagle, General Hospital/Harvard Medical School, Boston reported receiving grants from BMS/Pfizer,
Goldhaber, Bikdeli); Thrombosis Research Group, (Dua); Vascular Medicine, Cleveland Clinic Main Janssen, Alexion, Bayer, Amgen, and BSC paid to
Brigham and Women’s Hospital, Harvard Medical Campus, Cleveland, Ohio (Tefera); Heart and the institution and personal fees from BSC, Amgen,
School, Boston, Massachusetts (Piazza, Vascular Service, OhioHealth Riverside Methodist BCRI, PERC, Syntactx, BMS, and Janssen outside
Krishnathasan, Hamade, Ujueta, Scimeca, Hospital, Columbus (Kolluri); Columbia University the submitted work. Dr Monreal reported receiving
McGonagle, Goldhaber, Bikdeli); Department of Irving Medical Center, New York, New York (Parikh); grants from Sanofi and Rovi outside the submitted
Medicine, Brigham and Women’s Hospital, Harvard Medicine and Surgery, University of Insubria, work. Dr Fanikos reported receiving personal fees
Medical School, Boston, Massachusetts Varese, Italy (Ageno); Thrombosis and from AstraZeneca, Pfizer, and Anthos outside the
(Ortiz-Rios); Department of Medicine, Sunnybrook Atherosclerosis Research Institute, Hamilton Health submitted work. Dr Kolluri reported receiving
Health Sciences Centre, University of Toronto, Sciences, and McMaster University, Hamilton, personal fees from Abbott, Auxetics, Daiichi
Toronto, Ontario, Canada (Galanaud); Servicio de Ontario, Canada (Weitz); Department of Medicine, Sankyo, Koya Medical, Medtronic, Penumbra,
Neumología, Hospital Ramón y Cajal e Instituto F. Edward Hebert School of Medicine, The Philips, Surmodics, USA Therm, and VB Devices;
Ramón y Cajal de Investigación Sanitaria (IRYCIS), Uniformed Services University of the Health serving as a board member of The VIVA Foundation
Madrid, Spain (Jiménez); Departamento de Sciences, Bethesda, Maryland (Moores); Service de and The Intersocietal Accreditation
Medicina, Universidad de Alcalá, Instituto Ramón y Médecine Vasculaire, CHU Montpellier, UMR UA11 Council-Vascular Testing; and serving as president
Cajal de Investigación Sanitaria, Madrid, Spain INSERM IDESP – Montpellier University, of the Syntropic CoreLab outside the submitted
work. Dr Parikh reported receiving grants from

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 Superficial Vein Thrombosis: A Review Review Clinical Review & Education

Abbott Vascular, Boston Scientific, Reflow Medical, J Haematol. 2015;168(5):639-645. doi:10.1111/bjh. Haematol. 2023;10(5):e359-e366. doi:10.1016/
Cagent Vascular, Concept Medical, and Veryan 13255 S2352-3026(23)00013-3
Medical and personal fees from Medtronic, Philips, 6. Rountree KM, Barazi H, Aulick NF. Mondor 20. Gaukroger PB, Roberts JG, Manners TA.
Cordis, Shockwave Medical, Terumo, Inari, disease. Accessed January 14, 2025. https://www. Infusion thrombophlebitis: a prospective
Penumbra, and Akura Medical outside the ncbi.nlm.nih.gov/pubmed/30855866 comparison of 645 Vialon and Teflon cannulae in
submitted work. Dr Ageno reported serving on anaesthetic and postoperative use. Anaesth
advisory boards for AstraZeneca, Bayer, Norgine, 7. Decousus H, Prandoni P, Mismetti P, et al;
CALISTO Study Group. Fondaparinux for the Intensive Care. 1988;16(3):265-271. doi:10.1177/
Sanofi, and Viatris outside the submitted work. Dr 0310057X8801600305
Weitz reported serving as a consultant for and treatment of superficial-vein thrombosis in the legs.
receiving honoraria from Alnylam, Bayer, N Engl J Med. 2010;363(13):1222-1232. doi:10.1056/ 21. Di Minno G, Mannucci PM, Tufano A, et al; First
Boehringer Ingelheim, Bristol Myers Squibb, Daiichi NEJMoa0912072 Ambulatory Screening On Thromboembolism (fast)
Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer, 8. Cosmi B, Filippini M, Tonti D, et al; STEFLUX Study Group. The first ambulatory screening on
Regeneron, and Servier outside the submitted Investigators. A randomized double-blind study of thromboembolism: a multicentre, cross-sectional,
work. Dr Quéré reported receiving personal fees low-molecular-weight heparin (parnaparin) for observational study on risk factors for venous
from Viatris outside the submitted work. Dr Bikdeli superficial vein thrombosis: STEFLUX (Superficial thromboembolism. J Thromb Haemost. 2005;3(7):
reported being supported by a Career Development ThromboEmbolism and Fluxum). J Thromb Haemost. 1459-1466. doi:10.1111/j.1538-7836.2005.01458.x
Award from the American Heart Association and 2012;10(6):1026-1035. doi:10.1111/j.1538-7836.2012. 22. Giannoukas A, Karathanos C, Nikolakopoulos K,
VIVA Physicians (#938814); was previously 04727.x et al; SeVEN Collaborators. Tinzaparin in
supported by the Scott Schoen and Nancy Adams 9. Cosmi B. Management of superficial vein intermediate dose for the treatment of superficial
IGNITE Award and is supported by the Mary Ann thrombosis. J Thromb Haemost. 2015;13(7):1175-1183. vein thrombosis: results from an observational
Tynan Research Scientist award from the Mary doi:10.1111/jth.12986 multicenter study-SeVEN study. Phlebology. 2018;
Horrigan Connors Center for Women’s Health and 33(9):636-645. doi:10.1177/0268355517748540
Gender Biology at Brigham and Women’s Hospital 10. Kushner A, West WP, Khan Suheb MZ,
Pillarisetty LS. Virchow Triad. StatPearls; 2024. 23. Karathanos C, Chatzis D, Latzios P, Papakostas
and the Heart and Vascular Center Junior Faculty I, Goumas K, Giannoukas AD; SeVEN EXT
Award from Brigham and Women’s Hospital; 11. Cosmi B, Filippini M, Campana F, et al; STEFLUX Collaborators. Treatment of superficial vein
reported serving as a consulting expert, on behalf Investigators. Risk factors for recurrent events in thrombosis with intermediate dose of tinzaparin:
of the plaintiff, for litigation related to 2 specific subjects with superficial vein thrombosis in the a real word cohort study: the SeVEN EXTension
brand models of IVC filters; being a member of the randomized clinical trial SteFlux (Superficial study. Phlebology. 2021;36(6):423-431. doi:10.1177/
medical advisory board for the VascuLearn Thromboembolism Fluxum). Thromb Res. 2014;133 0268355520947300
Network; serving in the data safety and monitory (2):196-202. doi:10.1016/j.thromres.2013.12.005
board of the NAIL-IT trial funded by the National 24. Galanaud JP, Genty C, Sevestre MA, et al;
12. Galanaud JP, Sevestre MA, Pernod G, et al. OPTIMEV SFMV investigators. Predictive factors for
Heart, Lung, and Blood Institute, and Translational Long-term risk of venous thromboembolism
Sciences; receiving compensation as an associate concurrent deep-vein thrombosis and symptomatic
recurrence after isolated superficial vein venous thromboembolic recurrence in case of
editor for the New England Journal of Medicine thrombosis. J Thromb Haemost. 2017;15(6):1123-1131.
Journal Watch Cardiology, as an associate editor for superficial venous thrombosis: the OPTIMEV study.
doi:10.1111/jth.13679 Thromb Haemost. 2011;105(1):31-39. doi:10.1160/
Thrombosis Research, and as an executive associate
editor for JACC, and a section editor for Thrombosis 13. Rabe E, Hoffmann U, Schimke A, et al; TH10-06-0406
and Haemostasis (no compensation) outside the INSIGHTS-SVT Study Collaborators. Determinants 25. Hirmerová J, Seidlerová J, Šubrt I, Hajšmanová
submitted work. No other disclosures were of late venous thromboembolic events after acute Z. Prevalence of cancer in patients with superficial
reported. isolated superficial vein thrombosis in daily vein thrombosis and its clinical importance. J Vasc
practice: 12 month results of the INSIGHTS-SVT Surg Venous Lymphat Disord. 2022;10(1):26-32. doi:
Submissions: We encourage authors to submit Study. Eur J Vasc Endovasc Surg. 2023;66(5):697-
papers for consideration as a Review. Please 10.1016/j.jvsv.2021.05.006
704. doi:10.1016/j.ejvs.2023.08.031
contact Kristin Walter, MD, at kristin.walter@ 26. Legnani C, Cini M, Cosmi B, Filippini M,
jamanetwork.org. 14. Bauersachs R, Gerlach HE, Heinken A, et al. Favaretto E, Palareti G. Inherited and acquired
Management and outcomes of patients with thrombophilic alterations in patients with
REFERENCES isolated superficial vein thrombosis under real life superficial vein thrombosis of lower limbs. Thromb
conditions (INSIGHTS-SVT). Eur J Vasc Endovasc Surg. Haemost. 2014;111(6):1194-1196. doi:10.1160/
1. Frappé P, Buchmuller-Cordier A, Bertoletti L, 2021;62(2):241-249. doi:10.1016/j.ejvs.2021.04.015
et al; STEPH Study Group. Annual diagnosis rate of TH13-11-0925
superficial vein thrombosis of the lower limbs: the 15. Patel SK, Surowiec SM. Venous insufficiency. 27. Sobreira ML, Rogatto SR, Dos Santos RM,
STEPH community-based study. J Thromb Haemost. Accessed January 14, 2025. https://www.ncbi.nlm. Santos IT, Ferrari IC, Yoshida WB. An unexpectedly
2014;12(6):831-838. doi:10.1111/jth.12575 nih.gov/pubmed/28613694 high rate of thrombophilia disorders in patients
2. Geersing GJ, Cazemier S, Rutten F, Fitzmaurice 16. Schamroth Pravda M, Yehuda D, Schamroth with superficial vein thrombosis of the lower
DA, Hoes AW. Incidence of superficial venous Pravda N, Krashin E. Risk factors for superficial extremities. Ann Vasc Surg. 2017;43:272-277. doi:
thrombosis in primary care and risk of subsequent thrombophlebitis: a retrospective case control 10.1016/j.avsg.2017.02.022
venous thromboembolic sequelae: a retrospective study. Isr Med Assoc J. 2022;25(12):847-850. 28. James AH. Venous thromboembolism in
cohort study performed with routine healthcare 17. Díez-Vidal A, Gómez López J, Rodríguez Fuertes pregnancy. Arterioscler Thromb Vasc Biol. 2009;29
data from the Netherlands. BMJ Open. 2018;8(4): P, et al. Superficial vein thrombosis and its (3):326-331. doi:10.1161/ATVBAHA.109.184127
e019967. doi:10.1136/bmjopen-2017-019967 relationship with malignancies: a prospective 29. Aaro LA, Johnson TR, Juergens JL. Acute
3. Wendelboe AM, Campbell J, Ding K, et al. observational study. J Thromb Thrombolysis. 2024; superficial venous thrombophlebitis associated
Incidence of venous thromboembolism in a racially 57(4):650-657. doi:10.1007/s11239-024-02963-6 with pregnancy. Am J Obstet Gynecol. 1967;97(4):
diverse population of Oklahoma County, Oklahoma. 18. Prandoni P, Casiglia E, Tikhonoff V, Leizorovicz 514-518. doi:10.1016/0002-9378(67)90565-0
Thromb Haemost. 2021;121(6):816-825. doi:10. A, Decousus H, Calisto I; Calisto Investigators. The 30. Bremme KA. Haemostatic changes in
1055/s-0040-1722189 risk of subsequent cancer and arterial pregnancy. Best Pract Res Clin Haematol. 2003;16
4. Allaert FA, Benzenine E, Quantin C. Hospital cardiovascular events in patients with superficial (2):153-168. doi:10.1016/S1521-6926(03)00021-5
incidence and annual rates of hospitalization for vein thrombosis in the legs. Blood. 2011;118(17):
4719-4722. doi:10.1182/blood-2011-06-364232 31. Antic D, Lefkou E, Otasevic V, et al; Balkan
venous thromboembolic disease in France and the Working Group for Prevention and Treatment of
USA. Phlebology. 2017;32(7):443-447. doi:10.1177/ 19. Wiegers HMG, Körmendiné Farkas D, Venous Thromboembolism. Position paper on the
0268355516653005 Horváth-Puhó E, Middeldorp S, van Es N, Sørensen management of pregnancy-associated superficial
5. Scott G, Mahdi AJ, Alikhan R. Superficial vein HT. Incidence and prognosis of superficial vein venous thrombosis. Clin Appl Thromb Hemost.
thrombosis: a current approach to management. Br thrombosis during pregnancy and the post-partum 2022;28:1076029620939181. doi:10.1177/
period: a Danish nationwide cohort study. Lancet 1076029620939181

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 Clinical Review & Education Review Superficial Vein Thrombosis: A Review

32. Olin JW, Young JR, Graor RA, Ruschhaupt WF, patients with superficial vein thrombosis: 58. Lozano FS, Almazan A. Low-molecular-weight
Bartholomew JR. The changing clinical spectrum of a systematic review and meta-analysis. J Thromb heparin versus saphenofemoral disconnection for
thromboangiitis obliterans (Buerger’s disease). Haemost. 2016;14(5):964-972. doi:10.1111/jth.13279 the treatment of above-knee greater saphenous
Circulation. 1990;82(5)(suppl):IV3-IV8. 46. Mathieu ME, Duffett L, Caiano L, et al. thrombophlebitis: a prospective study. Vasc
33. Olin JW. Thromboangiitis obliterans (Buerger’s Management and outcomes of superficial vein Endovascular Surg. 2003;37(6):415-420. doi:10.
disease). N Engl J Med. 2000;343(12):864-869. thrombosis: a single-center retrospective study. Res 1177/153857440303700605
doi:10.1056/NEJM200009213431207 Pract Thromb Haemost. 2023;8(1):102263. doi:10. 59. Grigorian A, Nahmias JT. Upper extremity deep
34. Tagalakis V, Kahn SR, Libman M, Blostein M. 1016/j.rpth.2023.102263 venous thrombosis. Accessed January 14, 2025.
The epidemiology of peripheral vein infusion 47. Di Nisio M, Peinemann F, Porreca E, Rutjes AW. https://www.ncbi.nlm.nih.gov/pubmed/29494027
thrombophlebitis: a critical review. Am J Med. Treatment for superficial infusion thrombophlebitis 60. Lim CS, Davies AH. Graduated compression
2002;113(2):146-151. doi:10.1016/S0002-9343(02) of the upper extremity. Cochrane Database Syst Rev. stockings. CMAJ. 2014;186(10):E391-E398. doi:10.
01163-4 2015;2015(11):CD011015. doi:10.1002/14651858. 1503/cmaj.131281
35. Khawaja HT, Campbell MJ, Weaver PC. Effect of CD011015.pub2 61. Cesarone MR, Belcaro G, Errichi S, et al. Topical
transdermal glyceryl trinitrate on the survival of 48. Cominacini M, De Marchi S, Tosi F, et al. heparin: new observations. Angiology. 2007;58(suppl
peripheral intravenous infusions: a double-blind Incidence and clinical progression of asymptomatic 1):16S-20S. doi:10.1177/0003319706297740
prospective clinical study. Br J Surg. 1988;75(12): peripherally inserted central catheter-related 62. Cabré F, Camacho JA, Rodríguez-Garcés CA,
1212-1215. doi:10.1002/bjs.1800751223 thrombosis in solid neoplasm patients: ultrasound Breier DV, Ballarin M. Review of topical sodium
36. Ong CK, Venkatesh SK, Lau GB, Wang SC. insights from a prospective cohort study. Res Pract heparin 1000 iu/g gel in symptomatic
Prospective randomized comparative evaluation of Thromb Haemost. 2024;8(3):102391. doi:10.1016/ uncomplicated superficial thrombophlebitis. Cureus.
proximal valve polyurethane and distal valve j.rpth.2024.102391 2023;15(10):e47418. doi:10.7759/cureus.47418
silicone peripherally inserted central catheters. 49. Meissner MH. Lower extremity venous 63. Di Nisio M, Wichers IM, Middeldorp S.
J Vasc Interv Radiol. 2010;21(8):1191-1196. doi:10. anatomy. Semin Intervent Radiol. 2005;22(3):147- Treatment for superficial thrombophlebitis of the
1016/j.jvir.2010.04.020 156. doi:10.1055/s-2005-921948 leg. Cochrane Database Syst Rev. 2013;(4):
37. Wildgruber M, Lueg C, Borgmeyer S, et al. 50. Chen KR. The misdiagnosis of superficial CD004982. doi:10.1002/14651858.CD004982.pub5
Polyurethane versus silicone catheters for central thrombophlebitis as cutaneous polyarteritis 64. Prandoni P, Tormene D, Pesavento R; Vesalio
venous port devices implanted at the forearm. Eur J nodosa: features of the internal elastic lamina and Investigators Group. High vs low doses of
Cancer. 2016;59:113-124. doi:10.1016/j.ejca.2016. the compact concentric muscular layer as low-molecular-weight heparin for the treatment of
02.011 diagnostic pitfalls. Am J Dermatopathol. 2010;32 superficial vein thrombosis of the legs:
38. Ploton G, Pistorius MA, Raimbeau A, et al. (7):688-693. doi:10.1097/DAD.0b013e3181d7759d a double-blind, randomized trial. J Thromb Haemost.
A STROBE cohort study of 755 deep and superficial 51. Stein PD, Hull RD, Patel KC, et al. D-dimer for 2005;3(6):1152-1157. doi:10.1111/j.1538-7836.2005.
upper-extremity vein thrombosis. Medicine the exclusion of acute venous thrombosis and 01391.x
(Baltimore). 2020;99(6):e18996. doi:10.1097/MD. pulmonary embolism: a systematic review. Ann 65. Frappé P, Bertoletti L, Le Hello C, Décousus H,
0000000000018996 Intern Med. 2004;140(8):589-602. doi:10.7326/ Laporte S. Evaluation of direct oral anticoagulants in
39. Carpentier PH, Maricq HR, Biro C, 0003-4819-140-8-200404200-00005 superficial-vein thrombosis. Lancet Haematol.
Ponçot-Makinen CO, Franco A. Prevalence, risk 52. Aguilar C, del Villar V. D-dimer is not useful for 2017;4(6):e254. doi:10.1016/S2352-3026(17)30062-
factors, and clinical patterns of chronic venous the diagnosis of isolated superficial venous 5
disorders of lower limbs: a population-based study thrombosis. Am J Med. 2005;118(12):1417. doi:10. 66. Titon JP, Auger D, Grange P, et al. [Therapeutic
in France. J Vasc Surg. 2004;40(4):650-659. 1016/j.amjmed.2005.06.044 management of superficial venous thrombosis with
doi:10.1016/j.jvs.2004.07.025 53. Liu W, He L, Zeng W, et al. D-dimer level for calcium nadroparin: dosage testing and comparison
40. Tepper NK, Marchbanks PA, Curtis KM. ruling out peripherally inserted central with a non-steroidal anti-inflammatory agent]. Ann
Superficial venous disease and combined hormonal catheter-associated upper extremity deep vein Cardiol Angeiol (Paris). 1994;43(3):160-166.
contraceptives: a systematic review. Contraception. thrombosis and superficial vein thrombosis. Nurs 67. Talasaz AH, Sadeghipour P, Ortega-Paz L, et al.
2016;94(3):275-279. doi:10.1016/j.contraception. Open. 2022;9(6):2899-2907. doi:10.1002/nop2.998 Optimizing antithrombotic therapy in patients with
2015.03.010 54. Gillet JL, Ffrench P, Hanss M, Allaert FA, coexisting cardiovascular and gastrointestinal
41. Binder B, Lackner HK, Salmhofer W, Kroemer S, Chleir F. [Predictive value of D-dimer assay in disease. Nat Rev Cardiol. 2024;21(8):574-592.
Custovic J, Hofmann-Wellenhof R. Association superficial thrombophlebitis of the lower limbs]. doi:10.1038/s41569-024-01003-3
between superficial vein thrombosis and deep vein J Mal Vasc. 2007;32(2):90-95. doi:10.1016/j.jmv. 68. Brown KR, Rossi PJ. Superficial venous disease.
thrombosis of the lower extremities. Arch Dermatol. 2007.01.111 Surg Clin North Am. 2013;93(4):963-982. doi:10.
2009;145(7):753-757. doi:10.1001/archdermatol. 55. Beyer-Westendorf J, Schellong SM, Gerlach H, 1016/j.suc.2013.04.007
2009.123 et al; SURPRISE investigators. Prevention of 69. Noppeney T, Rabe E, Hoffmann U, et al;
42. Chengelis DL, Bendick PJ, Glover JL, Brown thromboembolic complications in patients with INSIGHTS-SVT study group. Varicose vein surgery
OW, Ranval TJ. Progression of superficial venous superficial-vein thrombosis given rivaroxaban or after acute isolated superficial vein thrombosis in
thrombosis to deep vein thrombosis. J Vasc Surg. fondaparinux: the open-label, randomised, daily practice: INSIGHTS-SVT study. J Vasc Surg
1996;24(5):745-749. doi:10.1016/S0741-5214(96) non-inferiority SURPRISE phase 3b trial. Lancet Venous Lymphat Disord. 2024;12(6):101917. doi:10.
70007-1 Haematol. 2017;4(3):e105-e113. doi:10.1016/S2352- 1016/j.jvsv.2024.101917
43. Decousus H, Quéré I, Presles E, et al; POST 3026(17)30014-5
70. Gloviczki P, Lawrence PF, Wasan SM, et al. The
(Prospective Observational Superficial 56. Superficial Thrombophlebitis Treated By 2023 Society for Vascular Surgery, American
Thrombophlebitis) Study Group. Superficial venous Enoxaparin Study Group. A pilot randomized Venous Forum, and American Vein and Lymphatic
thrombosis and venous thromboembolism: a large, double-blind comparison of a low-molecular-weight Society clinical practice guidelines for the
prospective epidemiologic study. Ann Intern Med. heparin, a nonsteroidal anti-inflammatory agent, management of varicose veins of the lower
2010;152(4):218-224. doi:10.7326/0003-4819-152- and placebo in the treatment of superficial vein extremities: part II: endorsed by the Society of
4-201002160-00006 thrombosis. Arch Intern Med. 2003;163(14):1657- Interventional Radiology and the Society for
44. Decousus H, Leizorovicz A. Superficial 1663. doi:10.1001/archinte.163.14.1657 Vascular Medicine. J Vasc Surg Venous Lymphat
thrombophlebitis of the legs: still a lot to learn. 57. Boehler K, Kittler H, Stolkovich S, Tzaneva S. Disord. 2024;12(1):101670. doi:10.1016/j.jvsv.2023.
J Thromb Haemost. 2005;3(6):1149-1151. doi:10.1111/ Therapeutic effect of compression stockings versus 08.011
j.1538-7836.2005.01445.x no compression on isolated superficial vein 71. Quere I, Elias A, Maufus M, et al. [Unresolved
45. Di Minno MN, Ambrosino P, Ambrosini F, thrombosis of the legs: a randomized clinical trial. questions on venous thromboembolic disease.
Tremoli E, Di Minno G, Dentali F. Prevalence of deep Eur J Vasc Endovasc Surg. 2014;48(4):465-471. Consensus statement of the French Society for
vein thrombosis and pulmonary embolism in doi:10.1016/j.ejvs.2014.06.047

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 Superficial Vein Thrombosis: A Review Review Clinical Review & Education

Vascular Medicine (SFMV)]. J Med Vasc. 2019;44(1): 75. Nikolakopoulos KM, Kakkos SK, observational studies. J Thromb Haemost. 2012;10
e1-e47. doi:10.1016/j.jdmv.2018.12.178 Papageorgopoulou CP, Tsolakis IA. (6):1004-1011. doi:10.1111/j.1538-7836.2012.04704.x
72. Stevens SM, Woller SC, Kreuziger LB, et al. Extended-duration treatment of superficial vein 79. Bailey AJM, Luo OD, Zhou SQ, Wells PS. The
Antithrombotic therapy for VTE disease: second thrombosis of the lower limbs with tinzaparin. Vasc incidence and risk of venous thromboembolism in
update of the CHEST Guideline and Expert Panel Specialist Int. 2018;34(1):1-9. doi:10.5758/vsi.2018. patients with active malignancy and isolated
Report. Chest. 2021;160(6):e545-e608. doi:10. 34.1.1 superficial venous thrombosis: a systematic review
1016/j.chest.2021.07.055 76. Anuforo A, Evbayekha E, Agwuegbo C, et al. and meta-analysis (the IROVAM-iSVT review).
73. Twine CP, Kakkos SK, Aboyans V, et al; ESVS Superficial venous disease-an updated review. Ann J Thromb Haemost. 2025;23(6):1824-1837. doi:10.
Guidelines Committee; Document Reviewers. Vasc Surg. 2024;105:106-124. doi:10.1016/j.avsg. 1016/j.jtha.2025.03.019
Editor’s choice: European Society for Vascular 2024.01.009 80. Dubois-Silva Á, Barbagelata-López C,
Surgery (ESVS) 2023 Clinical Practice Guidelines on 77. Debourdeau P, Bertoletti L, Font C, et al; Riete Piñeiro-Parga P, et al; RIETE Investigators.
Antithrombotic Therapy for Vascular Diseases. Eur J Investigators. Three-month outcomes in cancer Prognostic significance of concomitant superficial
Vasc Endovasc Surg. 2023;65(5):627-689. doi:10. patients with superficial or deep vein thrombosis in vein thrombosis in patients with deep vein
1016/j.ejvs.2023.03.042 the lower limbs: results from the RIETE Registry. thrombosis of the lower limbs. Thromb Haemost.
74. Bontinis A, Pouliopoulou I, Bontinis V, et al. Cancers (Basel). 2023;15(7):2034. doi:10.3390/ 2021;121(12):1650-1659. doi:10.1055/a-1414-5055
Anticoagulants for the treatment of isolated lower cancers15072034 81. Chopard R, Albertsen IE, Piazza G. Diagnosis
limb superficial vein thrombosis a Bayesian network 78. Galanaud JP, Bosson JL, Genty C, et al. and treatment of lower extremity venous
meta-analysis of randomized controlled trials. Superficial vein thrombosis and recurrent venous thromboembolism: a review. JAMA. 2020;324(17):
Thromb Res. 2024;241:109101. doi:10.1016/j. thromboembolism: a pooled analysis of two 1765-1776. doi:10.1001/jama.2020.17272
thromres.2024.109101

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