What are the risk factors for spontaneous phlebitis in the upper or lower extremities?

Causes of Spontaneous Phlebitis in Upper or Lower Extremities

Spontaneous phlebitis in the extremities is primarily caused by underlying malignancy, hypercoagulable states, and pre-existing varicose veins in the lower extremities, with approximately 20% of upper extremity cases and a significant proportion of lower extremity cases occurring without identifiable external triggers. 1, 2, 3

Lower Extremity Spontaneous Phlebitis

Primary Etiologic Factors

Varicose veins are the dominant predisposing factor, present in 86% of patients with superficial thrombophlebitis of the lower extremities. 4, 3 In the absence of malignancy, lower limb thrombophlebitis is invariably associated with pre-existing varicose veins. 3

Malignancy represents a critical systemic cause, particularly:

• Pancreatic, uterine, breast, and gastric cancers 1
• Advanced and metastatic disease 1
• Hematologic malignancies including lymphoma and acute leukemia 5
• Occult malignancy develops in approximately 10% of patients with so-called idiopathic venous thromboembolism 1

Hypercoagulable States

Inherited thrombophilias contribute to spontaneous phlebitis, though they typically require additional triggers:

• Protein C, protein S, or antithrombin III deficiencies 1
• Factor V Leiden or prothrombin mutations 1
• Hyperhomocysteinemia 1
• The prevalence of inherited coagulation defects ranges from 10% to 26% in upper extremity DVT patients 2

Acquired prothrombotic conditions include:

• Antiphospholipid syndrome 5
• Lupus anticoagulant or anticardiolipin antibodies 1

Inflammatory and Autoimmune Conditions

Chronic inflammatory diseases serve as persistent provoking factors:

• Inflammatory bowel disease 5
• Rheumatoid arthritis 5
• Behçet's disease, particularly in Asian populations 5
• Systemic lupus erythematosus 1

Age-Related Risk

Age over 40 years is an independent risk factor, with incidence increasing exponentially with age. 1 This likely reflects higher frequency of medical illnesses and operations with advancing age. 1

Obesity has been confirmed as an independent risk factor for venous thromboembolism. 1

Upper Extremity Spontaneous Phlebitis

Epidemiology of Spontaneous Cases

Approximately 20% of upper extremity DVT cases are spontaneous (primary), occurring without identifiable external triggers such as catheters or devices. 2, 6

Primary UEDVT accounts for one-third of all cases, typically due to:

• Venous thoracic outlet syndrome (Paget-Schroetter syndrome/effort-related thrombosis) 1, 7
• Idiopathic causes 1, 7

Underlying Systemic Causes

Malignancy is a major driver of spontaneous upper extremity thrombosis:

• Cancer is present in a significant proportion of spontaneous UEDVT cases 1, 6
• Active cancer increases thrombosis risk through tumor-expressed procoagulants, vessel wall damage, and direct vascular compression 5

Hypercoagulable states are found in 10-26% of UEDVT patients:

• Inherited coagulation defects 2, 6
• Antiphospholipid syndrome 5

Cardiorespiratory and Immobility Factors

Major cardiorespiratory disorders predispose to spontaneous thrombosis:

• Myocardial infarction 1
• Congenital heart disease 1
• Congestive cardiac failure 1
• Chronic irreversible airways disease 1

Lower limb immobility from neurological conditions:

• Stroke 1
• Brain tumors 1
• Acute spinal injury 1

Hormonal and Metabolic Factors

Oral estrogens carry increased risk, though less with current low-dose formulations:

• Venous thromboembolism is 2-4 times more common in users versus controls 1
• Risk applies to both oral contraceptives and hormone replacement therapy 1

Smoking is an independent risk factor for pulmonary embolism and by extension venous thrombosis. 1

Clinical Pitfalls and Caveats

Multifactorial etiology is common: 46% of patients have two or more prothrombotic factors, and 18% have three or more risk factors. 5 This means clinicians should not stop searching after identifying one cause.

The association between superficial and deep vein thrombosis is controversial: While older studies reported frequencies of 12-44%, more recent large population studies show only 5.6% have concurrent DVT. 8 However, when immobilization is present as an additional risk factor, the association increases significantly (36% vs 14%). 8

Deep vein thrombosis and pulmonary embolism complicate superficial thrombophlebitis in 28% of cases, with most complications occurring before surgical intervention. 4 This underscores that "spontaneous" superficial phlebitis is not always benign.

Upper extremity DVT leads to pulmonary embolism in up to 36-40% of cases, contrary to outdated beliefs that PE from upper extremity sources is rare. 1, 7, 2, 6 This makes spontaneous UEDVT a serious condition requiring the same vigilance as lower extremity disease.