Superficial Thrombophlebitis and its Management

Epidemiology And Pathogenesis

Although SVT is a frequently observed condition, its incidence and prevalence have never been adequately assessed. The classic Tecumseh Community Health Study from 1973 reported that the incidence of SVT increases with age from 0.05 per 1000 per year in males in their third decade to 1.8 per 1000 per year in their eighth decade. In females the incidence similarly rises from 0.31 per 1000 per year to 2.2 per 1000 per year from their third decade to their eighth decade. A more recent retrospective cohort study from the Netherlands reported an SVT rate in primary care of 1.3 per 1000 person-years with a 4.1% rate of venous thromboembolic sequelae, more frequent in active cancer patients and less in those with varicose veins. Other studies have also demonstrated an increased prevalence of SVT in females. ^,

Overall, the incidence of lower extremity SVT has been reported to be 3% to 11% in the general population. A useful classification is the recognition that SVT may occur in two forms, those with, and those without varicose veins, or alternatively, SVT may be primary, involving the vein wall only, or secondary, involving a more systemic inflammatory process. Primary SVT is most common in the saphenous veins and their tributaries, followed by the upper extremity cephalic and basilic veins. The greater saphenous vein (GSV) is affected in 60% to 80% of cases, followed by the small saphenous vein (SSV) in 10% to 20%, and bilateral lower extremity SVT in 5% to 10%. Patients with varicose veins are affected far more frequently than in the general population, with a prevalence of SVT ranging from 4% to 62%. ^{, ,}

Risk factors can be classified in accordance with Virchow’s triad: endothelial injury from trauma or insertion of venous catheters; venous stasis as seen in varicosities; and hypercoagulable states such as factor V Leiden, prothrombin G mutation, protein C and protein S deficiency, antithrombin III abnormalities, and malignancies including both solid tumors and hematologic conditions of Hodgkin lymphoma, leukemia, thrombocytosis, polycythemia vera, cryoglobulinemia, and nocturnal paroxysmal hemoglobinura. ^, Patients in whom SVT develops without an inciting physical event or varicosities may need to be fully evaluated for the presence of such disorders.

Other secondary causes for the development of SVT include the use of oral contraceptives, hormonal replacement therapy, pregnancy, obesity, prolonged immobilization, recent surgery, trauma, sclerotherapy, history of venous thromboembolism, and some drugs (e.g., diazepam, amiodarone, vancomycin, heroin, some chemotherapy). Intravenous catheter use with or without bacterial infection places patients more at risk for the development of SVT. ^, In addition, patients with autoimmune disorders, including systemic lupus erythematosus and vasculitis, such as Behçet and Buerger disease, have also been identified as being susceptible to the development of SVT. A 2006 review of 2319 patients with Behçet disease found that 14.3% of these patients have vascular involvement. Of these 332 patients, 53.3% had SVT and 29.8% had DVT. Patients with Buerger disease appear to have an increased incidence of SVT because the inflammatory process involves small arteries and veins of the extremities. It can be diagnosed from biopsy findings of acute superficial thrombophlebitis showing the characteristic acute phase lesion – inflammation of all three layers of the vessel wall with occlusive cellular thrombosis.

The main concern related to SVT is the likelihood that the thrombus will extend into the deep veins, causing DVT and potential PE. Several older studies have evaluated this risk especially in relation to the proximity of GSV SVT to the deep veins. Chengelis et al. followed 263 patients with isolated SVT and performed follow-up ultrasound at 2 to 10 days (mean 6.3 days). Thirty (11%) patients experienced progression to DVT while not receiving anticoagulation. The most common site was propagation of the SVT in the GSV into the common femoral vein. In a small retrospective review, 185 patients with SVT and 370 age- and sex-matched controls were evaluated. A minority (13%) received nonsteroidal anti-inflammatory drugs (NSAIDs) or rarely low-molecular-weight heparin (LMWH) therapy. At 6 months, overall 2.7% had developed DVT and 0.5% PE. SVT conferred a 10-time increased risk of developing DVT compared with controls without SVT. A more recent meta-analysis found a pooled DVT and PE event rate of 9.3 to 16.6 events per 100 person-years after SVT in the absence of pharmacological treatment. These studies represent an estimate of the natural history of SVT progression. Another focused study evaluated the incidence of PE in 21 patients with isolated SVT in the thigh. Nuclear perfusion lung scans were performed within 3 hours of SVT diagnosis and demonstrated seven patients with PE (33%), including one symptomatic patient. Of note, there were no significant differences in the distance of the SVT from the common femoral vein, or the presence of common risk factors for thrombosis compared with those with SVT that did not experience a PE. Although a small study, these findings highlight the potential serious consequences of SVT and suggest the need for anticoagulant therapy to prevent these complications.

Two recent large studies have evaluated the epidemiology and natural history of SVT in patients, most of whom received medical therapy. In the POST trial, Decousas et al. prospectively followed a cohort of 844 consecutive patients with symptomatic SVT of the lower limbs confirmed by ultrasound testing. Patients with recent surgery within 10 days or SVT due to sclerotherapy in the previous 30 days were excluded. Patients were initially assessed for concomitant DVT, and then those with isolated SVT (634 patients) were followed with ultrasound again at 10 days and then at 3 months. A secondary outcome was overall mortality at 3 months. DVT or PE was confirmed in 24.9% of patients with SVT (82 patients with proximal DVT, 33 patients with PE). In 41.9% of patients with DVT, both proximal and distal, the DVT was not contiguous with the SVT. Of 634 patients with SVT, 90.5% received one or more anticoagulant medications, mostly therapeutic LMWH. Sixty patients (10.2%) had venous surgery. Fourteen patients were lost to follow-up. Of the remaining 586 patients, 58 had thromboembolic complications (10.2%), including seven with symptomatic proximal DVT, three with PE, and five with extension of SVT to DVT. Multivariate analysis showed that male sex, history of DVT or PE, previous cancer, and no varicose veins were independent risk factors for symptomatic venous thromboembolism (VTE) at 3 months including recurrence or extension of SVT. A more recent analysis of the ICARO study confirmed similar risk factors of male sex and cancer for progression of isolated SVT to DVT and PE.

A recent pooled analysis of the POST study and the OPTIMEV trials involving 1074 cases revealed that in symptomatic patients with SVT, only male sex significantly and independently increased the risk of VTE recurrence after multivariate analysis. Cancer and saphenofemoral/popliteal junction proximity were associated with VTE recurrence on univariate analysis.

The OPTIMEV study evaluated 788 patients with SVT of 8256 patients that were referred for VTE. The median age of these patients was 65 years, 36% were men and 16% were inpatients. Similar to the POST study, 29% were found to have concomitant DVT. Patients with both SVT and DVT had risk factors of presence of nonvaricose veins involved, age greater than 75 years, inpatient status, and active cancer, compared with isolated SVT, which was independently associated with anticoagulant treatment at inclusion and pregnancy or postpartum state. Compared with SVT of varicose veins, SVT in nonvaricose veins was a strong risk factor for concurrent DVT but did not convey a higher risk of 3-month adverse outcomes of death, VTE recurrence, or bleeding. In this study, 76% of those with isolated SVT were treated with anticoagulants, including 92.5% with full-dose LMWH. A follow-up analysis revealed that cancer patients with SVT have a poor prognosis similar to that of patients with cancer-related DVT suggesting that these patients may require a longer duration of anticoagulant therapy.

More recently, there has been greater awareness of the presence of hypercoagulable states in patients with SVT. These patients have a higher probability of developing DVT and recurrent SVT and may require long-term anticoagulation to prevent complications. Milio et al. evaluated 107 patients with unprovoked SVT for common thrombophilic conditions. The patients underwent duplex evaluation at baseline and every 48 hours for 8 days, with notation whether the SVT occurred in varicose or nonvaricose veins. In the overall cohort, factor V Leiden was detected in 22.4%, MTHRF in 17.7%, and factor II G20210 mutation in 8.4%. Patients with thrombophilia and SVT in nonvaricose veins had a higher rate of extension of thrombus to deep veins. However, because all patients were treated with either LMWH or NSAIDs and the results were not analyzed by treatment group, it is difficult to draw definitive conclusions regarding the role of thrombophilia and DVT extension. Similar studies have supported the presence of acquired and inherited thrombophilic disorders as being a risk factor for the development of SVT, such as factor V Leiden and prothrombin (G20210A) gene mutations; deficiencies of antithrombin, heparin cofactor 2, protein C, and protein S; lupus anticoagulant; anticardiolipin antibodies; and abnormal fibrinolytic activity. ^{, , , ,}

An analysis published in 2014 including 1294 patients with SVT concluded that in patients with SVT not associated with varicose veins, malignancy, or autoimmune disease, thrombophilia screening may be considered due to a higher incidence of thrombus progression.

Although a number of studies have described the pathophysiology and various changes that take place in leukocyte–vessel wall interactions, cytokines/chemokines, and various other factors involved in the development and resolution of DVT, there is a paucity of studies exploring these mechanisms in SVT. In a study of 68 patients with leg SVT who were treated with low and intermediate doses of dalteparin, acute phase SVT showed elevated high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), interleukins 6, 8 and 10 (IL-6, IL-8, IL-10), and markers of fibrinolytic activity tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen that were reduced with treatment. Higher inflammatory markers were negatively correlated with thrombus recanalization at 12 weeks.

Clinical Presentation

Evaluation for SVT by physical examination is based on the presence of erythema and tenderness in the distribution of the superficial veins and with the thrombosis being suspected by a palpable cord. Pain, erythema, and swelling are the most common symptoms. There are a number of conditions discussed later that present unique risk factors or clinical presentations of SVT.