Thrombophlebitis
Synonyms and keywords: White Leg; phlebitis

# Overview
Thrombophlebitis is inflammation of a vein, usually associated with the formation of a thrombus within the superficial venous system. It can occur in any superficial venous system, but most commonly in the lower limbs. Symptoms of thrombophlebitis include pain along the course of the vein, redness, itching and swelling around the site of thrombophlebitis. The treatment of thrombophlebitis consists of compression stockings, analgesia, as well as anticoagulants. The most feared complications are DVT and PE.

# Historical Perspective
- In 1913, Burnham AC discussed thrombophlebitis in postoperative patients.
- Historically, the treatment of thrombophlebitis was purely surgical and consisted of removal of the thrombosed vein.

# Classification
Thrombophlebitis can be classified according to the cause into:
Thrombophlebitis may also be classified according to the site into:
- Superficial thrombophlebitis of the lower limb: most common location and it involves the great and short saphenous veins.
- Superficial thrombophlebitis of the arms
- Superficial thrombophlebitis of the breast: also known as Mondor's disease
- Superficial thrombophlebitis of the abdominal wall

# Pathophysiology

## Pathogenesis
The pathogenesis of thrombophlebitis is related to 3 important factors:
- Venous stasis
- Hypercoagulability of blood
- Trauma to veins
These 3 factors (known as Virchow's triad) predispose to thrombus formation within the veins and subsequently to thrombophlebitis.

## Associated Conditions
Thrombophlebitis may be associated with the following conditions:
- Coagulation abnormalities:
Factor V Leiden mutation
Prothrombin G20210A mutation
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
- Factor V Leiden mutation
- Prothrombin G20210A mutation
- Protein C deficiency
- Protein S deficiency
- Antithrombin III deficiency
- Thromboangiitis obliterans (Buerger's Disease)
- Underlying malignancy, especially adenocarcinoma of the pancreas in the case of migratory thrombophlebitis

# Causes

## Common Causes
- Deep vein thrombosis
- Drug side effects
- Intravenous infusion
- IV catheter infection
- Levamisole-induced vasculopathy
- Penicillin G potassium infusion
- Thromboangiitis obliterans
- Thrombophlebitis migrans
- Varicose veins
- Vein injury

# Differentiating Thrombophlebitis from other Diseases
Thrombophlebitis must be differentiated from the following conditions causing pain, swelling and palpapable mass in the extremities:

# Epidemiology and Demographics

## Epidemiology

### Incidence
- The incidence of thrombophlebitis is estimated at 100 per 100,000 cases.
- Thrombophlebitis is 6 times more common than DVT.

## Demographics

### Age
- Thrombophlebitis is more common in elderly.

# Risk Factors
The following are associated with an increased risk of thrombophlebitis:
- Chronic venous disease, such as varicose veins (most common risk factor) and chronic venous insufficiency
- Venous thrombosis, whether a prior history or current DVT
- Venous stasis, associated with prolonged immobility and prolonged surgery
- Hypercoagulable states, such as malignancy, pregnancy and the use of estrogen-based hormone therapy
- Trauma to the vessel, such as IV cannulation, sclerotherapy and surgical ablation
- Obesity

# Natural History, Complications and Prognosis

## Natural History
Thrombophlebitis was thought of as a benign condition. However, if left untreated, thrombophlebitis can recur or extend to involve the deep venous system. DVT can still complicate 10% of cases, despite treatment.

## Complications
Complications of thrombophlebitis include:
- Venous thromboembolism and subsequent pulmonary embolism: this is especially common when superficial thrombophlebitis occurs at the junction with the deep venous system
- Hyperpigmentation of the skin overlying the affected vein
- Infection and abscess formation

## Prognosis
The prognosis of thrombophlebitis is generally good with medical treatment. However, despite treatment, DVT can complicate about 10% of cases of thrombophlebitis.

# Screening
There are no screening recommendations for thrombophlebitis.

# Diagnosis

## History and Symptoms
The following symptoms are often (but not always) present in patients with thrombophlebitis:
- Pain along the course of the affected vein
- Pain on touch of the affected vein (tenderness)
- Skin redness (erythema)
- Itching
- Swelling of the surrounding tissue (edema)
- Elevated temperature (fever) may or may not be present

## Physical Examination
Examination of the skin and affected area reveals the following:
- Tenderness along the course of the affected vein
- Erythema of the skin surrounding the vein
- Edema of the surrounding tissue

## Laboratory Findings

### D-Dimer
D-Dimer is not a useful laboratory test in the diagnosis of isolated cases of superficial thrombophlebitis. However, it may be useful in the case of a concomitant DVT.

## Ultrasound

### Venous Duplex Ultrasound
Although the diagnosis of thrombophlebitis is mostly clinical, venous Duplex ultrasound is considered the imaging of choice in suspected cases. Venous Duplex ultrasound can identify the following:
- Thickening of the wall of the vein, which may be associated with perivenous or subcutaneous edema
- A thrombus may or may not be present within the superficial venous system
- DVT may exist along with superficial thrombophlebitis, especially when thrombophlebitis involves the proximal great saphenous vein
- Ruling out other pathologies such as a popliteal cyst or muscle mass, which may be responsible for the patient's complaints

## Other Imaging Findings
There are no other imaging findings associated with thrombophlebitis.

## Other Diagnostic Studies
There are no other diagnostic studies associated with thrombophlebitis.

# Treatment

## Medical Therapy
The following interventions are used as a mainstay in treatment of thrombophlebitis:

### Nonsteroidal Anti-Inflammatory Drugs
All NSAIDs have the same effect in the treatment of thrombophlebitis.  They are effective in reducing the pain, and decrease the extension of thrombosis.

### Anticoagulation
- Unlike minimal thrombophlebitis that can be resolved using conservative measures and NSAIDs, severe cases need anticoagulation therapy to prevent thrombus extension.
- Low molecular weight heparin is considered the treatment of choice, and proved to be superior to the NSAID in preventing extension of superficial thrombophlebitis.
- Other anticoagulants which may be used include warfarin, unfractionated heparin or fondaparinux.

### Topical Agents
Some topical anti-inflammatory agents (e.g. diclofenac gel) has been found to reduce the pain, and help resolution of the inflammation.

### Antibiotics
When suppurative thrombophlebitis is suspected, antibiotic treatment should be started.

## Surgery
Conservative measures and medical therapy are considered the first line treatment for patients with thrombophlebitis. However, patients with recurrent thrombophlebitis are candidates for surgical intervention, such as venous stripping or ligation.

# Prevention

## Primary Prevention
The following preventive measures can be done to decrease the incidence of thrombophlebitis:
- Encourage early mobilization after surgery to prevent venous stasis
- Avoid prolonged cannulation or change cannula after no more than 48 hours
- Consider anticoagulants for patients with coagulation disorders or hypercoagulable states

## Secondary Prevention
Medical therapy with anticoagulants can decrease the rate of recurrence of thrombophlebitis.