Superficial vein thrombosis: State of art. A review

Abstract

Objectives

Superficial venous thrombosis (SVT) is an acute thrombosis affecting the superficial venous system, characterized by inflammation of the venous wall. While much research has focused on deep vein thrombosis (DVT), SVT has historically been neglected due to its reputation as a benign and self-limiting condition.

Methods

A literature search was conducted using PubMed and Google Scholar from January 2000 to December 2023, focusing on English-language publications and including original articles, systematic reviews, and randomized controlled trials. The following keywords were used in various combinations: “superficial venous thrombosis,” “superficial thrombophlebitis,” “phlebitis,” and “thrombophlebitis.” The review aimed to analyze SVT, discuss its key features, treatment approaches, and prognosis. We identified 133 potentially relevant records, of which 98 were screened in full text; 39 met our inclusion criteria (i.e., adult populations, clinical data on SVT incidence, risk factors, and treatment outcomes). A PRISMA-style flowchart illustrates the selection process and reasons for exclusion (e.g., duplication, lack of relevant endpoints).

Results

SVT is a common but often underestimated condition that can lead to complications, including pulmonary embolism. The mainstay treatment consists of anticoagulant therapy, starting with low-dose unfractionated heparin or fondaparinux as the first-line drug, progressing to oral anticoagulants at therapeutic doses in more extensive cases. The diagnosis is primarily clinical but should be confirmed by color Doppler ultrasound. Furthermore, SVT may be indicative of serious underlying conditions.

Conclusions

While often considered benign, SVT is a deceptive pathology. If not properly diagnosed and treated, it can progress to DVT and associated complications. Additionally, SVT may signal significant systemic conditions such as malignancies, hereditary thrombophilia, and cardiovascular diseases, warranting further investigation by clinicians.

Keywords

Superficial vein thrombosis ultrasound risk factor management

Definition

With the definition of superficial venous thrombosis (SVT), also known as superficial thrombophlebitis, we refer to a pathological condition characterized by the formation of thrombi within superficial veins, accompanied by involvement or occlusion of the lumen and an inflammatory reaction along the venous pathway.^1,2

The term superficial thrombophlebitis is no longer commonly used, as it refers mainly to the inflammatory component of the process, which is often a secondary manifestation and not the determining cause of the thrombotic condition.³

SVT is more common in the superficial venous system of the lower limbs. Clinically, SVT presents as a tender, cord-like induration along the course of the involved vein. The involved area typically exhibits localized erythema, warmth, and swelling, with the vein feeling firm to palpation.¹

Method

We identified 133 potentially relevant articles, of which 98 were screened; 39 met our inclusion criteria (i.e., adult populations, clinical data on SVT incidence, risk factors, and treatment outcomes). A PRISMA-style flowchart (Figure 1) illustrates the selection process and reasons for exclusion (e.g., duplication, lack of relevant endpoints).

Figure 1.

PRISMA Flowchart. The PRISMA flow diagram for the systematic review detailing the database searches, the number of records identified, screened and excluded.

Epidemiology

The incidence of SVT in the general population ranges from 3% to 11%.⁴ However, these percentages are likely underestimated, as only the most symptomatic cases seek medical evaluation.

The average age at the time of diagnosis is 60 years, with older patients being less likely to present with the typical risk factors for SVT development.

The prevalence is higher among women (50%–70%) and increases with age.⁵

SVT more commonly affects the superficial venous system of the lower limbs, particularly the great saphenous vein (60%–80%), followed by the small saphenous vein (10%–20%).⁵ When the thrombotic process occurs in a varicose vein (varicophlebitis), it is often confined to the varicose tributaries rather than the saphenous trunks.⁶ The prevalence of SVT in patients with varicose veins ranges from 4% to 59%.⁵

The coexistence of concomitant deep vein thrombosis (DVT) in patients with superficial venous thrombosis (SVT) is highly variable, with percentages in the literature ranging between 2.6% and 65%. This wide variation may be attributed to differences in the characteristics of the populations studied, the diagnostic tools employed, and the study designs analyzed.³

DVT appears contiguous in 50%–75% of cases, extending from the superficial to the deep venous system or vice versa through the saphenous-femoral and saphenous-popliteal junctions, or via perforating veins.³

Evidence reported the prevalence of symptomatic pulmonary embolism (PE) ranging from 0.5% to 4% of patients with SVT, while as regards asymptomatic PE, systemic lung imaging in patients with SVT reveal asymptomatic emboli in up to 30% of cases.³ Although clinical PE is rare in SVT, systematic investigations may uncover a higher rate of silent embolism. Several studies indicate that thrombus extension from the superficial to the deep venous system occurs in roughly 10%–20% of SVT cases. For instance, in controlled trials assessing antithrombotic therapy in SVT, extension into the DVT was noted in approximately 18% of cases. Data on the prevalence of DVT extending into the superficial venous network are less abundant. However, in patients with proximal DVT, involvement of the superficial veins (either by extension or concomitant thrombosis) is estimated to occur in about 15%–20% of cases.⁷

Few studies have examined the risk of thromboembolic complications in patients with untreated SVT. Reported rates of such complications range from 1.7% to 26%.³

Important insights come from two prospective studies that followed patients with SVT over time:

(1) The Prospective Observational Superficial Thrombophlebitis (POST) study: Among 600 patients with isolated SVT (i.e., without DVT or PE at baseline), 10.4% (n = 56) developed venous thromboembolic complications within 3 months. These included symptomatic events such as PE (0.4%, n = 2), DVT (2.8%, n = 15), SVT extension (3.1%, n = 17), and SVT recurrence (1.9%, n = 10). Notably, these complications occurred despite the use of anticoagulant therapies in 90.5% (n = 540) of patients. Four independent risk factors were identified as increasing the risk of complications: male sex, cardiac or respiratory insufficiency, a history of DVT or PE, and the absence of a history of varicose veins.⁸

(2) The OPTIMEV study: in this study, 788 patients with SVT were prospectively evaluated over 3 months. At diagnosis, DVT was identified in 29% of cases. During follow-up, patients with isolated SVT had a lower mortality rate than those with SVT associated with DVT (1.2% vs 9.3%). Age >75 years, active cancer, hospitalization, and superficial thrombophlebitis of non-varicose veins were independently associated with the risk of developing DVT. SVT involving non-varicose veins was more frequently associated with DVT or PE (39.4% vs 23.3%).⁹

A subsequent pooled analysis of two multicenter, prospective observational studies evaluated predictors of DVT in an unselected population of patients with SVT.

A total of 1074 subjects with isolated SVT were followed for 3 months. During this period, 3.9% of subjects developed recurrent DVT, and 16.2% of subjects did not receive any anticoagulant therapy.

Active cancer, a personal history of DVT, and involvement of the saphenous-femoral or saphenous-popliteal junction significantly increased the risk of DVT and PE in multivariate analysis; conversely, male gender was associated with an increased risk of recurrence of SVT and PE in univariate analysis.³

In another study involving 138 patients with SVT (mean age: 61 ± 14 years, 36.2% men), most cases (89.9%) were associated with varicophlebitis, and approximately one-third of cases (34.1%) involved DVT or PE. Higher body mass index and the presence of the factor V Leiden mutation were independently associated with concomitant DVT or PE.¹⁰

Recently a systematic review and meta-analysis of a total 6842 patient reported at the time of SVT diagnosis, a prevalence of DVT of 18.1% and a prevalence of PE of 6.9%¹¹

Pathophysiology

Similar to DVT, SVT develops as a result of one or more components of Virchow’s triad: hypercoagulability, endothelial wall damage, and venous stasis.⁵

Venous stasis contributes to the thrombotic process by causing local accumulation of activated coagulation factors and reducing their clearance. It also promotes the accumulation of adenosine diphosphate, which stimulates platelet adhesion and aggregation. Furthermore, stasis leads to localized hypoxia, contributing to endothelial cell activation and damage. This results in the production of procoagulant substances and a decrease in the release of fibrinolysis activators.⁵

Etiological factors

The etiology of SVT remains unclear. In cases of varicophlebitis, the primary risk factors include venous stasis and damage to the diseased vein wall. In rare cases involving SVT of normal superficial veins, a triggering cause can often be identified, such as trauma, an insect bite, pregnancy, reduced mobility, or a sclerosant injection. Additionally, SVT may be associated with immunological syndromes (e.g., Trousseau, Lemierre, or Mondor syndromes) or inflammatory diseases such as thromboangiitis obliterans.¹

It is crucial to thoroughly investigate the presence of significant predisposing conditions, including:

• Neoplasms

• Collagen diseases

• Hypercoagulable states (e.g., resistance to activated protein C, antithrombin III deficiency, protein C or protein S deficiency, antiphospholipid antibodies, hyperhomocysteinemia, or the prothrombin G20210A mutation)

• Metabolic diseases

• Internal medicine conditions

• Cardiovascular diseases

• Hormone use for contraception or menopausal replacement therapy.^3,12–15

Below, we have analyzed in detail some of the primary risk factors for SVT.

Pregnancy

Pregnancy increases from three to four-fold the risk of thromboembolic phenomena. This elevated risk primarily stems from the hypercoagulable state of pregnancy, which likely serves as a protective mechanism to mitigate bleeding risks associated with spontaneous abortion and delivery.

Hypercoagulability develops as early as the first trimester, along with the associated increased risk of thrombosis.¹⁴

Coagulation disorders

Thrombophilia is a clotting disorder characterized by an increased tendency for arterial and/or venous thrombosis. It can be classified into hereditary and acquired forms.

Acquired thrombophilia includes conditions such as:

• Heparin-induced thrombocytopenia

• Antiphospholipid syndrome

• Malignancies

• Use of oral contraceptives

• Obesity

• Smoking

• Surgery

Hereditary thrombophilia encompasses several genetic disorders, most of which are transmitted in an autosomal dominant manner. Notable examples include:

• Factor V Leiden mutation (G1691A)

• Prothrombin mutation (G20210A)

• Deficiencies in antithrombin III, protein C, or protein S

Thrombophilia is associated with an increased risk of DVT, particularly in uncommon sites such as the splanchnic veins, cerebral veins, and retinal veins, and consequently pulmonary embolism (PE). However, the clinical manifestations of hereditary thrombophilia vary widely. Some individuals never develop thrombosis, while others may remain asymptomatic until adulthood, and some experience recurrent thromboembolism before the age of 30.¹⁵

• Coagulation Mechanisms in Thrombophilia

• Examining the coagulation pathway (see Figure 2) highlights the critical roles of activated Factor V (Va) and Factor VIII (VIIIa) in the formation of thrombin (Factor II) and subsequent clot formation. Factor V Leiden Mutation: This mutation in Factor V limits its inactivation, allowing the coagulation process to continue unchecked.

• Protein C and Protein S Deficiency: Protein C must be activated by free Protein S to form the activated protein C complex (APC), which is essential for inactivating Factor V. Deficiencies in Protein C and/or Protein S lead to a hypercoagulable state due to insufficient deactivation of Factor V (see Figure 2).

• Prothrombin G20210A Mutation (PTM): This is the second most common inherited thrombophilia after Factor V Leiden. It is characterized by a missense mutation in the 3’ untranslated region of the prothrombin (Factor II) gene. PTM is associated with elevated serum prothrombin levels, contributing to a hypercoagulable state and thromboembolic events.¹⁶

Figure 2.

The coagulation pathway.

Homocysteine

Homocysteine is an endogenous byproduct of the degradation of methionine, an amino acid found in dietary proteins and synthesized within the body. Under normal conditions, homocysteine is metabolized and excreted in the urine or recycled to form other proteins.¹⁷

Homocysteine metabolism

The recycling of homocysteine requires the participation of vitamins B12, B6, folic acid, and the enzyme methylene tetrahydrofolate reductase (MTHFR). Deficiencies in these vitamins or hereditary mutations in the gene encoding MTHFR impair the recycling process, leading to an accumulation of homocysteine in the blood.¹⁷

Homocysteine levels and classification

• Normal serum homocysteine levels: <15 μmol/L (upper limit of normal may vary between 13 and 14 μmol/L).

• Mild elevation: 15–30 μmol/L.

• Moderate elevation: 30–60 μmol/L.

• Severe elevation: >60 μmol/L.

• Rare cases of homocystinuria: Serum homocysteine >100 μmol/L.

Mildly elevated homocysteine levels are relatively common, affecting approximately 5%–7% of the general population.¹⁸

Clinical implications of elevated homocysteine

High homocysteine levels have been linked to:

• Increased risk of cardiovascular diseases.

• Greater risk of deep vein thrombosis (DVT).

• Pregnancy complications such as preeclampsia, placental abruption, and recurrent miscarriages.¹⁸

Elevated homocysteine levels are also more prevalent in women who have given birth to a child with neural tube defects (e.g., spina bifida or anencephaly). Consequently, folic acid supplementation at a dose of 0.4 mg/day is recommended for women of childbearing age to reduce the incidence of neural tube defects, regardless of individual homocysteine levels.¹⁸

Controversies in literature

While high homocysteine levels are associated with several conditions, the relationship remains controversial. It is unclear whether elevated homocysteine is an independent risk factor for atherosclerosis and thrombosis or merely a marker of underlying disease. The observation that homocysteine levels can be effectively reduced through the intake of vitamins B6, B12, and folic acid, yet this reduction is not associated with a concurrent decrease in the risk of cardiovascular disease or venous thrombosis, suggests that homocysteine may simply serve as a marker for these conditions rather than a direct cause.¹⁸

As a result, the American Heart Association stated in 2010 that the causal link between homocysteine levels and atherosclerosis has not been conclusively established.¹⁹

However, a recent document published in Circulation has clarified some concepts surrounding hyperhomocysteinemia, emphasizing that: (1) serum homocysteine testing should be limited to young individuals under the age of 20 or 30 who have experienced an unexplained cardiovascular or thrombotic event; (2) daily supplementation with folic acid, vitamin B6, or vitamin B12 is not recommended for the primary prevention of cardiovascular disease or deep vein thrombosis (DVT); and (3) there is no indication to test for MTHFR mutations in any patient population.¹⁹

Antiphospholipid syndrome

Antiphospholipid syndrome (APS) is present in 4%–20% of patients with venous thromboembolism. Antiphospholipid antibodies, including anticardiolipin antibodies, are often found in association with systemic lupus erythematosus, other autoimmune diseases, certain infections, and the use of specific drugs such as chlorpromazine, procainamide, and hydralazine.

The presence of antiphospholipid antibodies increases the risk of thromboembolic events by sixfold, while anticardiolipin antibodies are associated with a twofold increased risk.²⁰

APS is characterized by at least one episode of arterial or venous thrombosis, or a history of at least three spontaneous miscarriages before 10 weeks of pregnancy, one stillbirth after 10 weeks, or one pre-term delivery before 24 weeks. Laboratory diagnosis requires the detection of antiphospholipid antibodies or moderate-to-high values of immunoglobulin G (IgG) or anticardiolipin IgM antibodies on at least two occasions, at least 6 weeks apart. Approximately 80% of individuals with APS are female.²⁰

SARS-CoV-2 infection and increased thrombotic risk

Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19 (Co: corona; Vi: virus; D: disease; 19: the year of identification), has caused a global pandemic. While COVID-19 is commonly considered a respiratory disease, it is clear that the infection carries an inherent thrombotic risk.²¹

The disease is associated with an inflammatory, hypercoagulable, and hypofibrinolytic state, all of which favor thrombotic processes.²¹ Furthermore, thrombotic thrombocytopenia syndrome (TTS) has been observed after vaccination against COVID-19 using the Vaxzevria vaccine produced by AstraZeneca. This syndrome is characterized by serious thromboembolic events, including rare venous thrombosis of cerebral sinuses, splanchnic thrombosis, and arterial thrombosis, along with thrombocytopenia. TTS primarily affects women between the ages of 20 and 50, though no specific predisposing risk factors have been conclusively identified.²²

The pathogenesis of TTS appears to be linked to the production of anti-platelet factor 4 antibodies, a mechanism similar to that seen in heparin-induced thrombocytopenia.²²

Clinical presentation

The clinical onset of superficial venous thrombosis (SVT) is generally abrupt, with the patient experiencing sharp pain in the affected limb. This is often accompanied by a hard, reddened, and painful cord. Erythema and edema usually coexist in the affected limb, and fever may also be present.³

The veins of the lower limbs are most commonly affected: in about 60%–80% of cases, the great saphenous vein is involved, while in 10%–20% of cases, the small saphenous vein is affected. In 10%–20% of cases, other veins may also be involved.³

The veins of the upper limbs may also be affected, particularly when SVT is caused by a catheter in the basilic or subclavian vein. In such cases, the thrombotic process typically begins at the level of the catheter insertion and remains confined to the superficial vessel. However, it may sometimes extend to deep circulation through the confluence of the basilic vein into the axillary vein.³

Diagnosis

The diagnosis of SVT is primarily clinical, but it is always advisable to perform a color Doppler ultrasound to confirm the diagnosis.

In several studies, it has been observed that up to 50% of clinical diagnoses of SVT were not confirmed by color Doppler ultrasound, showing the higher accuracy of color Doppler ultrasound over clinical evaluation in the diagnosis of SVT.²² The ultrasound can localize the thrombotic process, evaluate its extent, assess its proximity to the sapheno-femoral and saphenous-popliteal junctions, and exclude involvement of the deep venous system.³

Echo color Doppler evaluation

Color Doppler ultrasound is the primary tool for diagnosing and screening vascular diseases. This non-invasive imaging technique provides real-time visualization of vessels (B-mode images) and allows for the assessment of blood flow within them (color map of the flow and Doppler flowmetry). The main advantages of this method include non-invasiveness, repeatability, low cost, and high diagnostic accuracy.

The examination is performed using a multifrequency linear probe (ranging from 4 to 18 MHz) or a multifrequency convex probe, especially for obese patients or those with significant edema.

Using the B-mode technique, a two-dimensional grayscale representation of the tissues is displayed. The gray gain should be adjusted so that the vessel lumen appears anechoic (black). The color map represents blood flow within the vessel, with different shades indicating varying flow speeds. This method also allows for visualization of the flow direction (toward or away from the probe). By convention, blue represents flow towards the heart.³

The Doppler wave is a graphical representation of the velocity and direction of blood flow. In the venous assessment, both the Doppler and the color scale should be set to detect slow flow (5–10 cm/sec) by using a low wall filter setting. Under normal conditions, venous flow is continuous and low speed, with rhythmic oscillations that correspond to the changes in intrathoracic pressure during respiration.³

To evaluate the venous circulation of the lower limbs, the patient should be in a supine position to assess the compressibility of the venous lumen, and in a standing position to examine valve competence.

For the diagnosis of SVT, the compression test in B-mode (Compression Ultrasound or CUS) is essential. This test is considered the “gold standard” for diagnosing both DVT and SVT. The examination begins with the identification of the saphenofemoral junction at the inguinal level, followed by a distal assessment of the great saphenous vein along the medial thigh and leg.

Next, with the patient in the prone position, the saphenopopliteal junction is located, and the small saphenous vein is examined along its entire course (medial/posterior leg).

In healthy veins, the vessel should be easily compressible, indicating the absence of thrombotic material. The diagnosis of SVT is confirmed by the presence of a non-compressible, hypoechoic area along the course of a superficial vein that is at least 5 cm in length.²³ Clot diameter under compression is measured, along with its distance from the saphenofemoral and popliteal junctions. If the clot is located ≤3 cm from the junction, the involvement of the saphenous junction is confirmed, and the treatment approach will be similar to that for DVT due to the higher risk of thrombus progression into the deep veins.^23,24

In the evaluation of veins in the upper limbs, the study is performed with a high-frequency linear probe and involves examining the following veins on both sides: internal and external jugular veins, subclavian veins above and below the clavicle, axillary veins, brachial veins, cephalic veins, basilic veins, and the median vein of the elbow.³

The diagnosis of superficial thrombophlebitis in the upper limbs follows the same method as in the lower limbs, using compression ultrasound.³

Other diagnostic methods

With the widespread use of color Doppler ultrasound for diagnosing suspected SVT and DVT, and considering its non-invasive, low-cost, and user-friendly characteristics, the routine use of computed tomography (CT), magnetic resonance imaging (MRI), and angiography is generally contraindicated. These methods are reserved for specific cases only.²⁴

Indications for CT or MRI include situations where ultrasound evaluation is inconclusive or technically difficult, such as suspected thrombosis in the pelvic veins or neoplastic thrombosis. In cases where color Doppler is not feasible, MRI is preferred over CT venography, particularly in pregnant women or patients who cannot tolerate iodinated contrast medium.³

Therapy

The treatment objectives for SVT are as follows:

1. To relieve symptoms (reduce inflammation along the involved veins and surrounding tissues).

2. To prevent the extension of thrombosis into the superficial and/or deep venous system.

3. To avoid recurrences.

4. To prevent thromboembolic complications such as DVT and PE.¹

Various treatment approaches have been proposed, ranging from topical therapies (e.g., topical anti-inflammatories and elastic compression) to systemic treatments (e.g., systemic anti-inflammatories, low molecular weight heparin, and oral anticoagulants). Other measures include behavioral recommendations (e.g., ambulation and resting in the Trendelenburg position) and surgical interventions (e.g., ligation of the great saphenous vein and saphenectomy).¹³

When planning the treatment for SVT, it is essential to consider the primary etiological factors and the contributions of various risk factors.

Compression and mobilization

Compression therapy and mobilization are the cornerstone treatments for SVT. Clinical experience shows that compressing the thrombosed vein helps relieve symptoms and accelerates healing. However, while this approach is widely considered crucial by most experts, randomized trials confirming its effectiveness are lacking.²⁵

The compression bandage should extend at least 10 cm beyond the proximal limit of the thrombosed area.²⁶ For thromboprophylaxis, anti-embolism socks are specifically designed to provide a controlled and consistent level of compression, typically around 18 ± 3 mmHg at the ankle, which helps to promote venous return and to reduce blood stasis, thereby lowering the risk of clot formation during periods of immobility. This level of compression is generally sufficient to achieve a prophylactic effect without causing discomfort during rest.³ In contrast, RAL [Reichs Ausschuss für Lieferbedingungen (State Commission for Delivery Terms)] Class I and Class II compression stockings are formulated for managing chronic venous disorders rather than for acute thromboprophylaxis. Although there are some overlaps in pressure ranges, for instance RAL Class I stockings usually offer a compression in the range of approximately 15–20 mmHg, while Class II stockings might provide between 20 and 30 mmHg, their primary goal is to alleviate symptoms of venous insufficiency, reduce edema, and improve overall venous hemodynamics over the long term.^3,26

Anti-embolism socks used for thromboprophylaxis are typically made of elastic material rather than short-stretch fabric. These elastic stockings are designed to provide a sustained, graduated level of compression (approximately 18 ± 3 mmHg at the ankle when at rest), which helps to promote venous return and to reduce blood stasis. In contrast, short-stretch bandages are generally used for other indications, such as lymphoedema management or post-surgical support, where a different compression profile is desired.²⁴

Regular walking further enhances the effectiveness of compression therapy on the lower limbs. Patients should walk regularly throughout the day and avoid prolonged periods of sitting or standing, as bed confinement can promote thrombus progression and is therefore strongly contraindicated.¹³

Medical therapy

Nonsteroidal anti-inflammatory drugs (NSAIDs), excluding aspirin, can be administered either locally or systemically.²⁷

These drugs help reduce pain and inflammation; however, there is no evidence to suggest that they reduce the incidence of thromboembolic events.²³ According to available data, NSAIDs have been shown to reduce the risk of the extension and/or recurrence of superficial venous thrombosis (SVT) by 67% compared to placebo. However, there were no significant differences observed in the incidence of deep vein thrombosis (DVT) or in the resolution of local symptoms and signs. Additionally, no bleeding episodes were reported in patients treated with either NSAIDs or placebo.^28,29

Anticoagulant therapy

Anticoagulant therapy is recommended for patients with extensive SVT who are at increased risk of DVT. However, this therapy is generally recommended for short-term use (less than 3 months), although the exact duration has not been definitively established.^30–32 Low molecular weight heparins (LMWH) are a valid option in treating SVT. The rationale for LMWH use is to neutralize and inhibit thrombin generation, thereby preventing thrombus extension and the occurrence of pulmonary embolism (PE).²⁹ Nevertheless, most studies evaluating anticoagulant therapy for SVT have been based on small sample sizes and have significant methodological weaknesses.^28–30 Tables 1 and 2 summarized the main evidence on treatment of SVT.

Table 1.

This table summarizes the key studies on SVT therapy, focusing on pharmacological approaches and the therapeutic results achieved.

Study	Treatment examined	Duration	Treatment groups	Key results
STENOX study	Enoxaparin (prophylactic vs therapeutic dose), NSAIDs, no treatment	10 days	1. Enoxaparin prophylactic (40 mg/day)	Enoxaparin, both at prophylactic and therapeutic doses, showed better therapeutic effects compared to the control and NSAID groups.
			2. Enoxaparin therapeutic (1.5 mg/kg/day)
			3. NSAIDs (tenoxicam 20 mg)
			4. No treatment (control group)
VESALIO study	Nadroparin (prophylactic vs therapeutic dose)	30 days	1. Nadroparin prophylactic (2850 IU anti-Xa)	No significant differences between prophylactic and therapeutic doses of nadroparin in treating SVT. Similar results for SVT progression and VTE complications
VESALIO study	Nadroparin (prophylactic vs therapeutic dose)	30 days	2. Nadroparin therapeutic (body weight-adjusted doses)
CALISTO study	Fondaparinux (2.5 mg/day) vs placebo	45 days	1. Fondaparinux (2.5 mg/day)	Fondaparinux significantly reduced the risk of complications (death, PE, DVT, SVT extension) compared to placebo. No increase in adverse events
CALISTO study	Fondaparinux (2.5 mg/day) vs placebo	45 days	2. Placebo
Rivaroxaban vs Fondaparinux study	Rivaroxaban (10 mg/day) vs Fondaparinux (2.5 mg/day)	45 days	1. Rivaroxaban (10 mg/day)	Rivaroxaban was non-inferior to fondaparinux for preventing complications (DVT, PE, SVT extension) and was not associated with more major bleeding
Rivaroxaban vs Fondaparinux study	Rivaroxaban (10 mg/day) vs Fondaparinux (2.5 mg/day)	45 days	2. Fondaparinux (2.5 mg/day)
Cochrane systematic review	LMWH and NSAIDs	-	1. LMWH (Low Molecular Weight Heparin)	LMWH and NSAIDs are considered the best therapeutic options for treating lower limb SVT
Cochrane systematic review	LMWH and NSAIDs	-	2. NSAIDs

Note. LMWH: Low Molecular Weight Heparin; NSAIDs: Non-Steroidal Anti-Inflammatory Drugs; PE: Pulmonary Embolism; SVT: Superficial Venous Thrombosis; DVT: Deep Venous Thrombosis.

Table 2.

Here is a table summarizing the main guidelines for the treatment of Superficial Venous Thrombosis (SVT), including anticoagulation recommendations, based on the most recent guidelines from SVS/AVF and Chest.

Guideline	Key recommendations	Anticoagulation recommendations	Citation
SVS/AVF (Society for Vascular Surgery/American Venous Forum)	SVT is often considered benign but requires proper treatment to avoid progression to DVT and complications	Anticoagulation is recommended in cases of extensive SVT (>5 cm), those with higher thrombotic risk, or those with involvement of the saphenous-femoral junction	SVS/AVF guidelines emphasize the use of LMWH and fondaparinux for anticoagulation in cases of extensive SVT or in high-risk patients Rivaroxaban is considered a reasonable alternative for anticoagulation in patients who refuse or are unable to use parenteral anticoagulation
	Anticoagulation is recommended in patients with extensive SVT or those at high risk for thromboembolic complications	LMWH (Low Molecular Weight Heparin) or fondaparinux is recommended for anticoagulation therapy
		If anticoagulation is not suitable, rivaroxaban (10 mg daily) can be used as an alternative
	Compression therapy is a cornerstone of treatment	Anticoagulation therapy should be continued for at least 3 months for cases near the saphenous-femoral junction
	Compression therapy is a cornerstone of treatment	In patients with additional risk factors for thromboembolism, anticoagulation is continued for 6 weeks
Chest guidelines (American College of Chest Physicians)	Similar to SVS/AVF, Chest guidelines emphasize the importance of anticoagulation in patients with extensive SVT or those at high risk of thromboembolic events.	For patients with SVT at increased risk of clot progression (such as those with involvement of the saphenous-femoral junction or those with previous VTE, cancer, or other comorbidities), oral anticoagulation with rivaroxaban is recommended	Chest guidelines strongly support rivaroxaban for anticoagulation in patients with high thromboembolic risk and fondaparinux for initial therapy
		LMWH or fondaparinux is preferred for initial anticoagulation, with rivaroxaban being recommended for those unable to use injectable options	Similar to SVS/AVF, the recommendations for anticoagulation therapy include a treatment duration of 3 months, with special consideration for those at high risk for recurrence or thromboembolic complications
		The use of oral anticoagulants should be continued for at least 3 months, particularly in patients with an extensive thrombotic process

Note. SVS: Society for Vascular Surgery; AVF: American Venous Forum; LMWH: Low Molecular Weight Heparin; PE: Pulmonary Embolism; SVT: Superficial Venous Thrombosis; DVT: Deep Venous Thrombosis.

In one study, no statistically significant differences were found in SVT regression or PE occurrence between low and high doses of nadroparin. A total of 164 patients with thrombophlebitis of the great saphenous vein were randomized to receive either prophylactic doses (2850 IU anti-Xa) or body weight-adjusted therapeutic doses of nadroparin for 30 days. The primary outcome of the study was to compare the rate of asymptomatic and symptomatic SVT extension or venous thromboembolic (VTE) complications over a 3-month follow-up period. Of the 81 patients receiving prophylactic doses, seven (8.6%) developed SVT progression or VTE complications compared to six of the 83 patients (7.2%) receiving the treatment group (absolute difference: 1.4%, 95% CI, −6.9 to 9.7; p = .74). No major bleeding events were reported in either group.²⁸

In another study, enoxaparin administered at a prophylactic dose (40 mg subcutaneously once a day) was associated with similar outcomes for PE prevention and reduction in SVT occurrence and extension when compared to larger doses (1.5 mg/kg once a day).²⁸ The STENOX study, which included patients with SVT of both varicose and non-varicose veins, compared four treatment schemes over 10 days: enoxaparin at a prophylactic dose (40 mg/day), enoxaparin at a therapeutic dose (1.5 mg/kg/day), oral NSAIDs (tenoxicam 20 mg), and no therapy (control group), with all groups prescribed elastic stockings. After 12 days, the therapeutic effect was higher in the three treated groups compared to the control group, and the enoxaparin groups were more effective than the NSAID-treated group.³⁰

The VESALIO study randomized patients with SVT of the great saphenous vein to two therapeutic regimens for 30 days: nadroparin at a prophylactic dose (2850 IU anti-Xa) or a body weight-adjusted therapeutic dose (7600–17100 IU anti-Xa). The main outcome of the study was the comparison of asymptomatic and symptomatic SVT extension or VTE complications over a 3-month follow-up period. Results showed no significant differences between the prophylactic and therapeutic dosing groups.³¹

The CALISTO study involved 3002 patients randomized to receive either fondaparinux 2.5 mg daily or a placebo for 45 days, with a 32-day additional monitoring period. The primary composite efficacy endpoint (death from any cause, symptomatic PE, symptomatic DVT, SVT extension to the saphenous-femoral junction, recurrence of SVT) occurred in 0.9% of the fondaparinux group and 5.9% of the placebo group, equating to a relative risk of 0.15 in the treated group. Serious adverse events occurred in 0.7% of patients on fondaparinux and 1.1% on placebo.³²

LMWH and NSAIDs are currently considered the best therapeutic options for treating SVT of the lower limbs, as confirmed by a Cochrane systematic review.³³

More recently, 435 subjects aged 18 years or older with symptomatic SVT involving a 5 cm or longer segment of a superficial vein above the knee and at least one risk factor for thromboembolic complications (e.g., age >65 years, male sex, history of SVT or DVT/PE, active cancer, autoimmune disease, non-varicose vein involvement) were randomized to receive either oral rivaroxaban 10 mg daily or subcutaneous fondaparinux 2.5 mg daily for 45 days. At the end of the follow-up, the primary efficacy outcome (incidence of death, symptomatic DVT or PE, proximal SVT extension, or recurrent SVT) occurred in 3% of patients in the rivaroxaban group and 2% in the fondaparinux group (hazard ratio [HR] 1.9; p = .0025 for non-inferiority). No major bleeding occurred in either group. Rivaroxaban was non-inferior to fondaparinux in terms of symptomatic DVT or PE, SVT progression or recurrence, and all-cause mortality, with no significant difference in major bleeding rates.³⁴

These findings have been incorporated into the American College of Chest Physicians guidelines, which recommend the use of anticoagulation with rivaroxaban for 45 days in patients with SVT of the lower limb at increased risk of clot progression, over no anticoagulation (weak recommendation, moderate-certainty evidence).³⁵

Practical therapeutic approach to SVT

In summary, the clinical management of superficial venous thrombosis (SVT) should consider the location and anatomy of the involved veins (whether they are collateral or tributary veins, or whether the saphenous-popliteal or saphenous-femoral junctions are affected), the extent of the thrombotic process, and the presence of any additional risk factors for thromboembolism.

For patients with SVT who do not involve the saphenous-popliteal or saphenous-femoral junctions and do not exhibit an increased risk of DVT, the treatment approach should include rest, local hot compresses, topical agents such as heparinoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and graduated elastic compression stockings¹ (Evidence level 2C).

For patients with SVT extending over 5 cm, those with increased thrombotic risk, or those showing clinical deterioration after 7 days of initial treatment, low molecular weight heparins (LMWHs) are recommended¹ (Evidence level 1B).

Fondaparinux 2.5 mg daily is considered the preferred treatment for SVT over other prophylactic or therapeutic doses of LMWHs (weak recommendation, low-certainty evidence).³¹ In patients who are unable or unwilling to use parenteral anticoagulation, rivaroxaban 10 mg daily is a reasonable alternative to fondaparinux 2.5 mg daily (weak recommendation, low-certainty evidence).² In cases of extensive thrombophlebitis (greater than 10 cm) with additional risk factors for venous thromboembolism, prophylactic fondaparinux therapy should be considered for a duration of 6 weeks.¹³

Medical therapy is generally considered superior to surgical therapy, which is currently only indicated for varicophlebitis once the acute phase has passed.¹³

For patients with extensive SVT near the saphenous-femoral junction (≤3 cm), oral anticoagulant therapy is indicated for at least 3 months, similar to the approach used in DVT (class I, level of evidence A).³⁶ The decision to continue anticoagulant therapy beyond 3 months is based on the individual’s thromboembolic and bleeding risk.

Non-vitamin K antagonist oral anticoagulants (NOACs)—such as dabigatran, apixaban, edoxaban, and rivaroxaban—are the preferred therapeutic options, given their lower bleeding risk compared to vitamin K antagonists (VKA).³⁶ These therapeutic regimens are the same as those approved for the treatment of DVT and pulmonary embolism,³⁶ (Figure 3).

Figure 3.

Practical therapeutic approach to SVT.

Special populations

• Antiphospholipid Syndrome: VKA are the only approved treatment for SVT in patients with antiphospholipid syndrome.³⁶

• Pregnancy: In the treatment of SVT and DVT during pregnancy, LMWH is preferred over unfractionated heparin, VKA, and NOACs. Fondaparinux and direct thrombin inhibitors should only be used in pregnant women who experience severe allergic reactions to heparin.¹⁴

• Breastfeeding: During breastfeeding, LMWH is preferable over fondaparinux, while warfarin or unfractionated heparin is preferred over NOACs.¹⁴

• Cancer Patients: The choice of anticoagulants in patients with cancer should balance the risk of venous thromboembolism (VTE) with the increased risk of bleeding. Treatment decisions should be individualized, considering factors such as mortality, quality of life, financial costs, and patient preferences. The American Society of Hematology 2021 guidelines suggest thromboprophylaxis for ambulatory cancer patients at low risk of VTE and the use of LMWH for initial treatment of VTE in cancer patients. Conditional recommendations include thromboprophylaxis for hospitalized cancer patients, LMWH or fondaparinux for surgical cancer patients, and LMWH or NOAC (apixaban, edoxaban, rivaroxaban) for high-risk ambulatory cancer patients. NOACs may also be used for short-term treatment of VTE in cancer patients, with LMWH or NOACs used for long-term treatment.³⁷

Conclusion

Although often considered a benign condition, SVT can be insidious. If not properly diagnosed and treated, SVT can progress to deep vein thrombosis (DVT) and its associated complications; it may also serve as an indicator of serious underlying systemic conditions, such as neoplasms, hereditary thrombophilia, and cardiovascular diseases, necessitating further investigation by the clinician.

Up to now, literature data are quite sparse, based mainly on reviews and observational studies, with few large, randomized controlled trials.

Looking ahead, future research should focus on (1) randomized trials comparing different anticoagulant agents (e.g., low-molecular-weight heparins vs direct oral anticoagulants) to determine the most effective and safe regimens for SVT, (2) comparative studies assessing the role of NSAIDs versus anticoagulants in preventing progression to deep vein thrombosis, and (3) investigations into optimal treatment duration in patients with specific risk factors such as active malignancy, pregnancy, or inherited thrombophilia. These efforts may help refine clinical protocols and minimize adverse outcomes in patients with SVT.

Key differences between guidelines

• SVS/AVF guidelines specifically mention rivaroxaban (10 mg daily) as an alternative to parenteral anticoagulation (e.g., LMWH or fondaparinux), while Chest guidelines focus more on oral anticoagulants and LMWH as preferred therapies for patients at increased risk of thromboembolism.

• Both sets of guidelines stress the importance of anticoagulation for patients with extensive SVT (involving the saphenous-femoral junction or over 5 cm in length), with a 3-month treatment period.

Footnotes

Author contributions

Each author significantly contributed to the manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Guarantor

Francesca Cortese.

ORCID iD

Francesca Cortese

Appendix

References

de Almeida

Guillaumon

Miquelin

, et al. Guidelines for superficial venous thrombosis. J Vasc Bras 2019; 18: e20180105.

Konstantinides

Meyer

. The 2019 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2019; 40(42): 3453–3455.

Tondi

. Patologie del sistema venoso e linfatico. Roma: Verducci Editore, 2013.

Geersing

G-J

Cazemier

Rutten

, et al. Incidence of superficial venous thrombosis in primary care and risk of subsequent venous thromboembolic sequelae: a retrospective cohort study performed with routine healthcare data from The Netherlands. BMJ Open 2018; 8(4): e019967.

Giannoukas

. Current management of superficial thrombophlebitis of the lower limb. Phlebolymphology, 2013.

Nicolaides

Allegra

Bergan

, et al. Management of chronic venous disorders of the lower limbs: guidelines according to scientific evidence. Int Angiol 2008; 27(1): 1–59.

Decousus

Frappé

Accassat

, et al. Epidemiology, diagnosis, treatment and management of superficial-vein thrombosis of the legs. Best Pract Res Clin Haematol 2012; 25(3): 275–284.

Decousus

Quéré

Presles

, et al. Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study. Ann Intern Med 2010; 152(4): 218–224.

Galanaud

J-P

Genty

Sevestre

M-A

, et al. Predictive factors for concurrent deep-vein thrombosis and symptomatic venous thromboembolic recurrence in case of superficial venous thrombosis. The OPTIMEV study. Thromb Haemost 2011; 105(1): 31–39.

10.

Hirmerova

Seidlerova

Subrt

. Deep vein thrombosis and/or pulmonary embolism concurrent with superficial vein thrombosis of the legs: cross-sectional single center study of prevalence and risk factors. Int Angiol 2013; 32(4): 410–416.

11.

Di Minno

MND

Ambrosino

Ambrosini

, et al. Prevalence of deep vein thrombosis and pulmonary embolism in patients with superficial vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2016; 14(5): 964–972.

12.

Falanga

. Thrombophilia in cancer. Semin Thromb Hemost 2005; 31(1): 104–110.

13.

Kalodiki

Stvrtinova

Allegra

, et al. Superficial vein thrombosis: a consensus statement. Int Angiol 2012; 31(3): 203–216.

14.

Andra

. Pregnancy and thrombotic risk. Crit Care Med 2010; 38(2 Suppl): S57–S63.

15.

Dautaj

Krasi

Bushati

, et al. Hereditary thrombophilia. Acta Biomed 2019; 90(10-S): 44–46.

16.

Elkattawy

Alyacoub

Singh

, et al. Prothrombin G20210A gene mutation-induced recurrent deep vein thrombosis and pulmonary embolism: case report and literature review. J Investig Med High Impact Case Rep 2022; 10.

17.

Cortese

Giordano

Scicchitano

, et al. Uric acid: from a biological advantage to a potential danger. A focus on cardiovascular effects. Vascul Pharmacol 2019; 120: 106565.

18.

Moll

Varga

. Homocysteine and MTHFR mutations. Circulation 2015; 132(1): e6–e9.

19.

Greenland

Alpert

Beller

, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2010; 56(25): e50–e103.

20.

Gloviczki

. Handbook of venous disorders: guidelines of the American Venous Forum. 3rd ed, 2008.

21.

Paul

Trujillo

. Coagulopathy, venous thromboembolism, and anticoagulation in patients with COVID-19. Pharmacotherapy 2020; 40(11): 1130–1151.

22.

Amin

Bashir

Joyce

, et al. An update on COVID-19 vaccine induced thrombotic thrombocytopenia syndrome and some management recommendations. Molecules 2021; 26(16): 5004.

23.

Quéré

Leizorovicz

Galanaud

J-P

, et al. Superficial venous thrombosis and compression ultrasound imaging. J Vasc Surg 2012; 56(4): 1032–1038.e1.

24.

Kearon

Akl

Comerota

, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e419S–e496S.

25.

Partsch

Rabe

Stemmer

. Superficial thrombosis. In Compression therapy of the extremities. Paris: Phlebologiques Francaises; 2000, pp. 300–304.

26.

Berszakiewicz

Sieroń

Krasiński

, et al. Compression therapy in venous diseases: current forms of compression materials and techniques. Postepy Dermatol Alergol 2019; 37(6): 836–841.

27.

Rathbun

Aston

Whitsett

. A randomized trial of dalteparin compared with ibuprofen for the treatment of superficial thrombophlebitis. J Thromb Haemost 2012; 10(5): 833–839.

28.

Titon

Auger

Grange

, et al. Therapeutic management of superficial venous thrombosis with calcium nadroparin. Dosage testing and comparison with a non-steroidal anti-inflammatory agent. Ann Cardiol Angeiol 1994; 43(3): 160–166.

29.

Superficial Thrombophlebitis Treated By Enoxaparin Study Group . A pilot randomized double-blind comparison of a low-molecular-weight heparin, a nonsteroidal anti-inflammatory agent, and placebo in the treatment of superficial vein thrombosis. Arch Intern Med 2003; 163(14): 1657–1663.

30.

Prandoni

Tormene

Pesavento

, et al. High vs. low doses of low-molecular-weight heparin for the treatment of superficial vein thrombosis of the legs: a double-blind, randomized trial. J Thromb Haemost 2005; 3(6): 1152–1157.

31.

The Vesalio Investigators Group . High vs. low doses of low-molecular-weight heparin for the treatment of superficial vein thrombosis of the legs: a double-blind, randomized trial. J Thromb Haemost 2005; 3: 1152–1157.

32.

Decousus

Prandoni

Mismetti

, et al. Fondaparinux for the treatment of superficialvein thrombosis in the legs. N Engl J Med 2010; 363(13): 1222–1232.

33.

Di Nisio

Wichers

Middeldorp

. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev 2007; 2(2): CD004982.

34.

Beyer-Westendorf

Schellong

Gerlach

, et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the openlabel, randomised, non-inferiority SURPRISE phase 3b trial. The Lancet Ematology; 4: e105–e113.

35.

Stevens

Woller

Baumann Kreuziger

, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. CHEST 2021; 160: e545–e608.

36.

Bates

Greer

Middeldorp

, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e691S–e736S.

37.

Lyman

Carrier

, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021; 5(4): 927–974.