Continuing Education Activity

Superficial thrombophlebitis, increasingly known as superficial venous thrombosis, is no longer considered a benign entity. It is often associated with concomitant deep venous thrombosis or pulmonary embolism, potentially due to a more sinister underlying issue. As such, there is limited consensus on treatment, which makes further study of this topic necessary. This activity reviews the evaluation and management of superficial venous thrombosis and highlights the healthcare team's role in evaluating and treating patients with this condition.

Objectives:

• Identify the etiology of superficial thrombophlebitis.
• Identify critical elements in the evaluation of patients with superficial thrombophlebitis that predispose patients to concomitant deep vein thrombosis and pulmonary embolism.
• Outline the management options available for superficial thrombophlebitis.
• Describe interprofessional team strategies to improve coordination of care and communication to advance the diagnosis of superficial thrombophlebitis and concomitant deep venous thrombosis and pulmonary embolism and more sinister underlying causes and thereby improve outcomes.

Introduction

Superficial thrombophlebitis is an inflammatory disorder of superficial veins with coexistent venous thrombosis.[1][2] It usually affects lower limbs, particularly the great saphenous vein (60% to 80%) or the small/short saphenous vein (10% to 20%). However, it can occur at other sites (10% to 20%) and may occur bilaterally (5% to 10%).[3][4] Traditionally, this relatively common process was considered benign and self-limited. More recently, superficial thrombophlebitis, also called superficial venous thrombosis (SVT), has been associated with other venous thromboembolic disorders, primarily deep venous thrombosis (DVT) and pulmonary embolism (PE). Therefore, it involves more than a purely clinical diagnosis with supportive treatment.[1][2][3][4][5] Affected patients have an increased risk for recurrence of venous thromboembolic events.[4] Herein, the terms of superficial thrombophlebitis and superficial venous thrombosis will be used interchangeably.

Etiology

A hypercoagulable state, prolonged immobilization, or vessel wall trauma may increase the risk of SVT. Superficial thrombophlebitis accounts for 5.4% of the adjusted population attributable risk for initial DVT or PE. SVT has been the presenting symptom in certain inheritable thrombophilias. According to several studies, it occurs in 11% to 15% of patients with protein C or S deficiency and approximately 40% of patients with factor V Leiden mutation.[5] However, another study showed that these results were not statistically significant.[6] 

In pregnancy, the risk of SVT is akin to that of DVT, most commonly in the postpartum period. Advanced age, exogenous estrogens, autoimmune or infectious diseases, obesity, recent trauma or surgery, active malignancy, history of venous thromboembolic disease, and respiratory or cardiac failure also increase the risk of SVT.[2][3][4][6] Prior occurrences increase the risk of subsequent ones. As noted in 75% to 88% of cases, varicose veins are considered the most important clinically identifiable predisposing factor for SVT.[2][3][4][5][6]

Epidemiology

The true incidence of superficial thrombophlebitis is unclear. In France, one community-based study noted the incidence of SVT to be 0.64%, while a different community-based study found the incidence to be half that of DVT and similar to PE.[3][6] Other studies suggest its prevalence in the general population is two to six times higher than the incidence of DVT and PE.[2][4][6] SVT is commonly seen in the outpatient population; usually, women, who made up 50% to 70% of the affected patients in one study; 60 years mean age; a body mass index that exceeds 25 kg/m2; and in those with varicose veins.[2][3][6]

For people who have a history of SVT, the lifetime risk of DVT or PE increases four to six times. While the three-month mortality is about 5% in patients with DVT or PE, it is less than 1% for those with SVT. One suggested reason for the lower mortality in patients with SVT is the younger age of the patients with fewer associated comorbidities.[3] The migration of the thrombus towards the deep veins at the saphenofemoral junction, the saphenopopliteal junction, or from a perforating vein during a state of hypercoagulability may cause the association between SVT and DVT or PE.[3][6] 

Pathophysiology

Superficial thrombophlebitis starts with microscopic thrombosis. When there is venous turbulence or stasis, vessel wall injuries, abnormal coagulability, or vessel wall injuries, microthrombi could propagate and subsequently form macroscopic thrombi. Vascular endothelial injury reliably results in thrombus formation by triggering an inflammatory response that results in immediate platelet adhesion. Platelet aggregation is mediated by thrombin and thromboxane A2.

History and Physical

Patients with superficial thrombophlebitis typically present with a reddened, warm, inflamed, tender area overlying the track of a superficial vein. There is often a palpable cord. Some surrounding edema or associated pruritis may occur. Significant swelling of the limb is more commonly associated with DVT and should only be attributed to SVT after DVT has been excluded.[1][2][3][6][7] Patients may have a history of antecedent trauma, which can include intravenous cannulation or infusion of irritants, such as recent sclerotherapy for varicose veins.[2][8]

A careful history is critical to identify risk factors for venous thromboembolism. Initial presentation in patients older than 40 years without other risk factors should prompt consideration of underlying malignancy.[2][6] Patients with migratory thrombophlebitis, a well documented paraneoplastic phenomenon, should also be further evaluated for underlying malignancy.[2][6][9] Migratory thrombophlebitis is usually associated with pancreatic or other visceral malignancies and is often referred to as Trousseau syndrome. It can be the presenting complaint in 5% to 15% of pancreatic cancer, particularly of the body and tail.[6][9][10]

Evaluation

Traditionally, superficial thrombophlebitis was a clinical diagnosis. However, with the increased realization of association with concomitant DVT or PE, compressive ultrasonography is recommended.[2][5][6] Physical examination does not adequately identify the extent of disease; it has been shown to underestimate it in up to 77% of instances. Compressive ultrasonography can identify concomitant DVT, evaluate the extent of the thrombus, and confirm the diagnosis.[2][6] The Prospective Observational Superficial Thrombophlebitis (POST) study reviewed venous duplex screening of the affected lower limb and showed that 23.5% of patients had concurrent DVT. More than half of these DVTs were not contiguous with the SVT; 17% were noted to affect the contralateral lower extremity, while only 1% had an isolated DVT in the contralateral limb. These findings support the regular use of ultrasound to evaluate SVT. The POST study also sought to establish the ultrasonic findings that increased the likelihood of associated DVT. It found that the risk substantially increased if a perforating vein was involved, with an odds ratio of 8.1, or if there was an SVT present less than 3 cm from the saphenofemoral junction, which had an odds ratio of 3.3.[6]

D-dimer testing is of limited utility in detecting SVT. It is variably elevated in SVT and cannot be used to distinguish isolated SVT from DVT.[2]

Experts debate whether patients who present with extensive superficial thrombophlebitis without an apparent inciting reason should have an evaluation for thrombophilia, given that hypercoagulability is associated with SVT. However, to date, there have been no conclusive studies identifying causation between hypercoagulability and SVT.[2]

As previously mentioned, migratory thrombophlebitis warrants evaluation for visceral neoplasm. Patients older than 40 years with their first episode of thrombophlebitis should also be evaluated for underlying neoplasm.[6][9] Superficial thrombophlebitis of the superficial breast veins is referred to as Mondor disease. A case series from 1992 noted a 12.7% risk of associated breast cancer, but it was a limited study, so it is argued that the incidence could have been overrepresented. Therefore, mammography could be considered in patients with this presentation.[6]

To help establish the pretest probability for the presence of DVT in patients with SVT, the Internal Carotid Artery Occlusion (ICARO) Study Group has outlined the following five variables: 

• Active malignancy (1.5 points)
• Limb edema (1.5 points)
• Age of fifty years or more (1 point)
• A ropelike sign (-1 point)
• Unprovoked SVT (-1 point)[11]

The ICARO Study Group suggested this scoring system to help when assessing such patients for coexisting DVT:

• Low probability (less than zero points): 1.1% likelihood
• Intermediate probability (score of 0 to 1): 12.0% likelihood
• High probability (scored 1.5 or more points): 32.3% likelihood[11]

However, a more recent study using this scoring system does not support its validity.[12]

Treatment / Management

Despite the number of studies performed, there is still debate on the appropriate treatment for superficial thrombophlebitis.

Multiple strategies have been proposed to control symptoms and decrease the extension of thrombosis and risk for PE in low-risk superficial thrombophlebitis.[2] Low-risk thromboses are those not associated with the presence of or predisposition to other thromboembolic diseases. In these cases, the consensus is that nonsteroidal anti-inflammatory agents, heat, and anticoagulants are all reasonable.[7]

Those who are at higher risk include patients with an SVT in the lower extremity that is at least 5 cm in length; SVT proximal to the knee, especially within 10 cm of the saphenofemoral junction; the presence of severe symptoms; greater saphenous vein involvement; previous SVT/venous thromboembolic disease; active malignancy; or recent surgery.[6] Based on the Cochrane review published in 2018, these patients should receive fondaparinux 2.5 mg/day subcutaneously for 45 days.[1]

This Cochrane review also evaluated topical and surgical treatments but noted that the data is too limited regarding these treatments and their effects on venous thromboembolic disease, so further studies are recommended at this time.[1] Rivaroxaban 10 mg daily for 45 days was found to be non-inferior to fondaparinux in preventing venous thromboembolic complications with a comparable safety profile in the SURPRISE trial. However, the Cochrane review did recommend further research on its use and the other direct oral factor-X or thrombin inhibitors.[1][13] Additionally, it recommended further study on the use of nonsteroidal anti-inflammatory agents and low molecular weight heparins.[1]

In those patients who develop superficial thrombophlebitis from an infusion, multiple agents have been evaluated for treatment. Per the 2015 Cochrane review of this topic, there is no consensus recommendation on the safety, dose required, or therapy duration for topical treatments, nonsteroidal anti-inflammatory agents, or systemic anticoagulation.[8]

Practices in the United Kingdom suggest using compression stockings with or without additional therapies, but there is no current recommendation for or against their use in the United States of America.[2][6]

Antibiotics are useful only with clear infection.[2]

For Trousseau syndrome, the main priority is to eliminate the underlying malignancy. However, as this is commonly a challenge, heparin is the recommended treatment given that multiple pathways contribute to the development of the thrombus. Low molecular weight heparins have been used, but some have been less effective than heparin; therefore, further studies are recommended. Fondaparinux has also been evaluated but found to be less efficacious than heparin, and the utility of this agent also requires further study.[9] A case report on the topic recommended the initial treatment with heparin followed by oral anticoagulants but did not specify a particular agent or dosing schedule.[10]

Mondor disease, discussed separately, is usually self-limited and benign and will resolve in four to eight weeks. However, if it is due to vasculitis, malignancy, or a hypercoagulable state, treatment is aimed at the underlying cause.[14]

Differential Diagnosis

It is essential to keep superficial thrombophlebitis on the differential when evaluating a patient. Other considerations include cellulitis, other venous thromboembolic diseases, hematoma, lymphangitis, lymphedema, vasculitis, tendonitis or sports-related injuries, and venous insufficiency.[15][16][17][18][19]

Prognosis

The prognosis for Superficial thrombophlebitis is related to the underlying cause. In low-risk SVT, it is generally favorable, but there is a definite risk for recurrent disease. In those with higher risk SVT, the overall prognosis is also positive with appropriate treatment. For those with SVT due to underlying malignancy, the prognosis is related to the causative process.

Complications

DVT and PE are significant complications of superficial thrombophlebitis. Multiple studies have found concomitant DVT with SVT in 6 to 36% of patients. These same studies clinically suspected concomitant PE in 2 to 13%, and regular performance of lung scans revealed the rate of asymptomatic PE approached 33%.[3] Other retrospective studies from both primary and secondary/tertiary centers reported concomitant DVT or symptomatic PE on the initial presentation to be 25 to 30%. About 5 to 7% of these patients had symptomatic PE.[3][4] However, the incidence of coexisting PE increased to 17% with the use of a more rigorous screening process of asymptomatic patients.[4] Patients with thrombus up to 3 cm from the saphenofemoral junction should be treated for DVT, given that 14 to 70% progress to DVT.[4][5] 

Consultations

Consultation with a vascular surgeon may be sought in patients with Superficial thrombophlebitis who require anticoagulation but have contraindications to anticoagulation. It may also be an option in those with recurrent SVT in the setting of chronic venous insufficiency.[2][3][6]

Hematology/oncology consultation may also be considered in patients with underlying thrombophilias or malignancies.[2]

Deterrence and Patient Education

Patients should be educated on the likelihood and significance of disease propagation and recurrence based on their risk factors. They should be advised of the need for further evaluation in the presence of migratory thrombophlebitis or if they are more than 40 years old at the time of their initial presentation and are without other risk factors for venous thromboembolic disease.

Pearls and Other Issues

Patients with superficial thrombophlebitis should have compressive ultrasonography of both the affected and contralateral limb to evaluate for concomitant venous thromboembolic disease.

Anticoagulation with fondaparinux 2.5 mg/day should be considered in patients with superficial thrombophlebitis in the lower extremity that is at least 5 cm in length; SVT proximal to the knee, especially within 10 cm of the saphenofemoral junction; the presence of severe symptoms; greater saphenous vein involvement; previous SVT/venous thromboembolic disease; active malignancy; or recent surgery.

Experts do not routinely recommend investigation for thrombophilia and underlying malignancy.

In patients with migratory thrombophlebitis, further investigations for visceral malignancy should ensue.

Enhancing Healthcare Team Outcomes

Given the incidence of concomitant venous thromboembolic disease and the possibility of extension, it is paramount for health care team members to recognize that superficial thrombophlebitis is no longer considered a benign entity.[1][2][3][4][5] Thus, if non-providers observe such symptoms, the concern can be brought to the attention of providers. Providers should have a low threshold to ultrasound both the affected and contralateral limb to evaluate for concurrent venous thromboembolic disease.[2][5][6] [Level 1] Then, providers should treat accordingly.[1][2][5][6][13] [Level 2] The patients may also require further evaluation for thrombophilias according to existing guidelines.[2][5] [Level 1]

It is also important for the interprofessional health care team, comprised of clinicians, nurses, mid-level practitioners, and pharmacists, to recognize that migratory thrombophlebitis requires a team evaluation as it can be a rare presentation of visceral malignancy and for the best outcomes, a coordinated team effort to treat the patient.[6][9] [Level 5]