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Abstract

General Considerations

The incidence of superficial vein thrombosis (SVT) in the general population ranges from 3% to 11%.^1–4 The prevalence is 0.05 per 1000 men per year and 0.31 per 1000 women per year during the third decade of life, increasing to 1.8 per 1000 men per year and 2.2 per 1000 women per year during the eighth decade of life.³The mean age of presentation is 60 years^1,5–10and the older the patient, the fewer risk factors are present.^10,11 Superficial vein thrombosis is more common (50%-70%) in women.^{1,5,7,8,12–18}

The great saphenous system is involved in 60% to 80% of the patients, and the small saphenous system in 10% to 20%.^1,7,19,20Bilateral SVT is reported in 5% to 10% of the patients.^1,5,7,20,21

Development of SVT in patients with varicose veins ranges from 4% to 59%,^1,7,12,16,20 and it is confined more frequently to varicose tributaries rather than to the saphenous trunks.^1,16 Obesity, age, and protein S deficiency have been found as factors associated with SVT episodes in patients with varicose veins.²²

Superficial vein thrombosis in patients without varicose veins is found in 5% to 10% of all patients^7,8,23 and the etiology includes autoimmune disease (Behçet, Buerger, and Mondor disease),^4,5 malignancy,^4,5,21,24 thrombophilia,^{2,4–6,13,25–34} mechanical or chemical trauma or injury (venous infusion, catheter introduction),³⁵ radiation injury,³⁵ and bacterial or fungal infections.³⁵

Risk factors are the same as those for deep vein thrombosis (DVT)^13,36 including, previous thromboembolic events, long-haul flights,^37,38 pregnancy,^39,40 oral contraceptives, hormone replacement therapy, immobilization,^14,41 obesity, recent surgery,¹⁴ trauma,^14,41 and sclerotherapy.⁴²

Obesity as assessed by increased body mass index is associated with an increase in prothrombotic factors (fibrinogen, von Willebrand Factor, factor VII, and viscosity)⁴³ and is an independent risk factor not only for VTE^44–46 but also for SVT.^1,25,36

Superficial vein thrombosis may coexist with DVT in 6% to 53% of the patients presenting with SVT.^{4,7,12,15,16,20,47–58} The most common is extension from the great saphenous vein (GSV) into the femoral vein.²⁰ Superficial vein thrombosis of the GSV above knee is associated with 17% to 19% incidence of DVT whereas SVT confined to the below knee segment has an incidence of association only in 4% to 5% of the patients.^10,36,48 The DVT may complicate “isolated” SVT in a short term.^4,7,8,59 Superficial vein thrombosis is a risk factor for the development and recurrence of DVT.^1,4,7,19,60

Pulmonary embolism (PE) has been observed in 1.5% to 33% of patients with SVT.^{4,7,8,15,20,52,54,61,62} The PE was reported in 18% of the patients when the thrombotic process was in the GSV above the knee and 4% when in the small saphenous vein.²⁰ The PE may complicate isolated SVT in the short term (3-4 months after the episode of SVT).^7,8,36The SVT is a risk factor for development and recurrent PE.^1,4,7,19,60 It is unclear whether PE associated with SVT arises from extension to deep veins or from thrombus that is only in the superficial venous system.¹

The link between SVT and pregnancy remains unclear,^{1,13,39,40,63–65} and the prevalence is very low (0.05%-0.1%) but it may be underestimated as only symptomatic patients are included.^39,40

The SVT presents with local pain, warmth, erythema, swelling, and the superficial vein becomes solid like a cord.^1,5,66,29Diagnosis should include Duplex ultrasound for confirmation, estimation of thrombus extent, exclusion of DVT, and follow-up.^{4,5,9,10,17,20,21,49–53,56,57,67}

The term superficial thrombophlebitis should be discouraged because inflammation and infection are not the primary pathology.³⁵ It should be called SVT in order to avoid the unnecessary administration of antibiotics and the misconception that SVT is benign.

Treatment

The rationale and evidence for treatment as summarized in this chapter has been provided by a recent guideline document.³⁵

There is great variation in treatment. In a national cross-sectional and prospective epidemiologic cohort study in France,⁷ a total of 634 patients had isolated SVT at inclusion. Information about the treatment they received during the 3-month observation period was available for 597 patients. Of these patients, 540 (90.5%) received one or more anticoagulant drugs either at therapeutic doses 374 (62.9%) or at prophylactic doses 216 (36.7%) while 99 (16.8%) received vitamin K antagonists (VKAs). Elastic compression stockings was received by 584 (97.7%), topical nonsteroidal anti-inflammatory drugs (NSAIDs) by 278 (47.2%) and oral NSAID by 48 (8.2%), and 60 (10.2%) patients had venous surgery (stripping or ligation). Fourteen patients were lost to follow-up at 3 months. Among the remaining 586 patients, thromboembolic complications occurred in 58 (10.2%).

A randomized open trial involving 562 patients with SVT associated with varicose veins has shown that unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or VKA had equal efficacy and were superior to elastic compression or flush ligation combined with elastic compression with regard to SVT extension at 3 months.⁶⁸

A randomized double-blind trial involving 427 patients compared LMWH (enoxaparin 40 mg and 1.5 mg/kg) with a NSAID (tenoxicam) and placebo for 8 to 12 days.⁶⁹ Rates of DVT and SVT as detected by ultrasonography at 12 days was 30.6% in the placebo, 14.9% in the tenoxicam, 6.9% in the enoxaparin 1.5 mg/kg, and 8.3% in the enoxaparin 40 mg (P < .01).

In another open randomized trial involving 117 patients, LMWH (nadroparin) was superior to a NSAID in reducing symptoms at 6 days (P < .001) and 8 weeks (P = .007).⁷⁰

High doses of UFH twice daily (12 500 IU for 1 week followed by 10 000 IU for 3 weeks) were superior to prophylactic doses (5000) twice daily in 60 randomized patients. During the 6-month follow-up, the rate of asymptomatic involvement of the deep veins and/or symptomatic VTE was reduced from 20% in the prophylactic dose to 3.3% in the high-dose group (P = .05).⁷¹ However, when therapeutic doses of nadroparin were compared to prophylactic doses in another study, progression or VTE occurred in 7.2% and 8.6% of the patients, respectively.⁷²

In a systematic review that included 5 randomized controlled trials (RCTs),⁷³ pooling of the data was not possible due to their heterogeneity. Three of these studies had serious methodological drawbacks limiting the clinical applicability of their results. In the remaining 2 studies, a nonsignificant trend in favor of high-dose UFH compared to low-dose UFH for the prevention of VTE was observed in one and a nonsignificant trend in favor of short-term treatment with LMWH or NSAID as compared to placebo in respect to VTE was observed in the other. The authors recommended treatment with at least intermediate doses of LMWH.

Another systematic review on the treatment of SVT included 24 studies that were of poor methodological quality. The analysis included a total of 2469 patients⁷⁴ and treatment ranged from LMWH to NSAIDs, topical treatment, surgery, or wearing compression stockings. The LMWH studies were more rigorous. The conclusion was that both LMWH and NSAIDs significantly reduced the incidence of extension or recurrence of SVT by approximately 70% compared to placebo and both had similar safety and efficacy. The topical treatments improved local symptoms but there was no any report on the progression to DVT. Surgical treatment combined with elastic stockings was associated with lower rate of VTE and progression of SVT compared to elastic stockings alone. The authors recommended an intermediate dose of LMWH for at least 1 month and pointed out that further research was needed to assess the role of NSAIDs and LMWH, the optimal doses, and duration of treatment, and whether combination therapy may be more effective than single treatment.

A small RCT involving 72 patients compared LMWH (dalteparin) with a NSAID (ibuprofen) for 14 days.⁷⁵ There was extension of the thrombosis in 4 (11%) patients in the dalteparin group and in none in the ibuprofen group (P = .05). There was a significant reduction in pain in both the groups when compared to the baseline, but there was no difference in the reduction of pain between the groups during the treatment period or at 14 days. There was no statistical difference in the extension of thrombosis at 3 months after treatment was stopped.

A recent international randomized double-blind trial involving 3002 patients⁸ compared fondaparinux subcutaneously 2.5 mg once daily for 45 days to placebo. Eligible for inclusion were hospitalized or nonhospitalized patients 18 years or older with acute symptomatic lower limb SVT at least 5 cm long as confirmed by compression ultrasonography. Exclusion criteria were the interval between the onset of symptoms and planned randomization more than 3 weeks; treatment for cancer within the previous 6 months; presence of symptomatic or asymptomatic DVT, symptomatic documented PE, SVT associated with sclerotherapy or placement of an intravenous catheter, SVP located within 3 cm of the saphenofemoral junction, DVT or PE within the previous 6 months, if the patients with SVT had received an antithrombotic agent (other than aspirin at a dose of ≤325 mg per day) for more than 48 hours or a NSAID for more than 72 hours for the current episode, if in the investigator’s opinion a saphenofemoral junction ligation was required, major surgery within the previous 3 months, if there were conditions that could confer predisposition to bleeding including creatinine clearance <30 mL/min or platelet count <100 000/mm³, and finally women in childbearing age if they were pregnant. The primary efficacy outcome (death from any cause or symptomatic PE, symptomatic DVT, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of DVT at day 47) occurred in 0.9% of the patients in the fondaparinux group and 5.9% in the placebo group (P < .001). The rate of PE or DVT was 85% lower in the fondaparinux group. Similar risk reductions were observed at day 77. No difference was observed in major bleeding between the 2 groups.

A review of 6 studies comparing surgery to anticoagulation showed similar rates of SVT progression, but the incidence of VTE and complications was higher with surgery.⁷⁶ Surgical treatment with elastic stockings was associated with lower VT rate and SVT progression compared to elastic stockings alone.⁷⁷ In another study, no difference was seen between surgery and enoxaparin for 4 weeks.⁷⁸

Antibiotics have no role in the management of SVT^35,79 except in cases secondary to indwelling intravenous catheters. Hirudoids have some effect in alleviating pain and local inflammatory signs, and some topical agents (hirudoid cream, piroxicam cream, piroxicam patch) are available in some countries.⁷⁷ Local application of heparinoid cream was better than placebo.^80,81 Local application of heparin was reported to have effects on symptoms comparable to LMWH.⁸² Elastic stockings is traditionally used if tolerated as an adjunctive treatment together with anticoagulation.^5,31

Recommendations

All patients with SVT should have bilateral duplex scanning to exclude DVT (level of evidence: high). The LMWH in intermediate doses for at least 1 month is recommended (level of evidence: moderate). Fondaparinux 2.5 mg daily for at least 4 weeks is an effective treatment (level of evidence: high). Surgery is not better than LMWHs (level of evidence: low).

When thrombus is close to saphenofemoral or saphenopopliteal junctions, LMWHs in therapeutic doses or surgery (ligation) are both acceptable options depending on the patient’s characteristics and the treating physician’s preference (level of evidence: low).

For isolated SVT at the below knee segment confined to varicosities, local application of heparinoids, NSAIDs, and elastic stockings are acceptable treatment options (level of evidence: low).

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Superficial Vein Thrombosis

Abstract

General Considerations

Treatment

Recommendations

References