Thrombophlebitis, Superficial

By admin On Nov 6, 2023

Ovid: 5-Minute Sports Medicine Consult, The

Jeffrey M. Mjaanes

Michael Hanna

Basics

Description

Superficial thrombophlebitis is an inflammatory condition of the veins with clinical findings of pain, tenderness, induration, and erythema of a superficial vein with secondary thrombosis.
Septic (suppurative) thrombophlebitis types:
- Iatrogenic
- Infectious: Mainly syphilis and psittacosis
Aseptic thrombophlebitis types:
- Primary hypercoagulable states: Disorders with measurable defects in the proteins of the coagulation and/or fibrinolytic systems
- Secondary hypercoagulable states: Clinical conditions with a risk of thrombosis
System(s) affected: Cardiovascular
Synonym(s): Phlebitis; Phlebothrombosis; Superficial venous thrombosis
Abbreviations: DVT = deep vein thrombosis; LMWH = low-molecular-weight heparin

Pediatric Considerations

Pediatric: Subperiosteal abscesses of adjacent long bone may complicate.
Geriatric: Septic thrombophlebitis is more common; prognosis poorer.
Others: N/A

Pediatric Considerations

Warfarin and NSAIDs are contraindicated.
Associated with increased risk of aseptic superficial thrombophlebitis

Alert

Note: Potentially lethal misnomer is use of now abandoned term superficial femoral vein thrombosis, which is actually a DVT and should be treated as such.

Epidemiology

Incidence

Septic:
- Up to 10% of all nosocomial infections
- Incidence of catheter-related thrombophlebitis is 88/100,000.
- Develops in 4–8% if cutdown is performed
- More common in childhood
- Predominant gender: Male = Female
Aseptic primary hypercoagulable state:
- Antithrombin III and heparin cofactor II deficiency incidence is 50/100,000.
- Antithrombin III and heparin cofactor II deficiency: Neonatal period, but 1st episode usually at age 20–30 yrs
- Proteins C and S deficiency: Before age 30
Aseptic secondary hypercoagulable state:
- Trousseau syndrome incidence in malignancy 5–15%
- Trousseau syndrome incidence in pancreatic carcinoma 50%
- In pregnancy, 49-fold increased incidence of phlebitis
- Superficial migratory thrombophlebitis in 27% of patients with thromboangiitis obliterans
- Mondor disease (superficial phlebitis of the breast): Women ages 21–55 yrs; also can occur in dorsal penile vein in men
- Thromboangiitis obliterans onset: 20–50 yrs
- Predominant gender: Mondor: Female > Male (2:1); thromboangiitis obliterans: Female > Male (1–19% of clinical cases)

Risk Factors

Nonspecific:
- Immobilization
- Obesity
- Advanced age
- Postoperative states
Septic:
- IV catheter
- Duration of IV catheterization (68% of cannulas have been left in place for 2 days)
- Emergent placement of catheter
- Cutdowns
- Cancer, debilitating diseases
- Steroids
- Incidence is 40 times higher with plastic cannulas (8%) than with steel or scalp cannulas (0.2%)
- Thrombosis
- Dermal infection
- Burn patients
- Lower extremities IV catheter
- IV antibiotics
- AIDS
- Varicose veins
Antithrombin II and heparin cofactor II deficiency:
- Pregnancy
- Oral contraceptives
- Surgery, trauma, infection
In pregnancy;
- Increased age
- HTN
- Eclampsia
- Increased parity
Thromboangiitis obliterans: Persistent smoking
Mondor disease:
- Breast abscess
- Antecedent breast surgery
- Breast augmentation
- Reduction mammoplasty

Genetics

Septic: No known genetic pattern
Antithrombin III deficiencies: Autosomal dominant
Proteins C and S deficiency: Autosomal dominant with variable penetrance
Disorders of fibrinolytic system: Congenital defects, inheritance variable
Dysfibrinogenemia: Autosomal dominant
Factor XII deficiency: Autosomal recessive

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General Prevention

Use of scalp vein cannulas
Avoidance of lower extremity cannulations
Insertion under aseptic conditions
Secure anchoring of the cannulas
Replacement of cannulas, connecting tubing, and IV fluid every 48–72 hr
Neomycin-polymyxin B-bacitracin ointment in cutdown

Etiology

Septic:
- Staphylococcus aureus in 65–78%
- Enterobacteriaceae, especially Klebsiella
- Multiple organisms in 14%
- Anaerobic isolate rare
- Candida spp.
- Cytomegalovirus in AIDS patients
Aseptic primary hypercoagulable state:
- Antithrombin III and heparin II deficiency
- Protein C and protein S deficiency
- Disorder of tissue plasminogen activator
- Abnormal plasminogen and coplasminogen
- Dysfibrinogenemia
- Factor XII deficiency
- Lupus anticoagulant and anticardiolipin antibody syndrome
Aseptic secondary hypercoagulable states:
- Malignancy (Trousseau syndrome: Recurrent migratory thrombophlebitis): Seen most commonly in metastatic mucin or adenocarcinomas of the GI tract (pancreas, stomach, colon, and gall bladder), lung, prostate, ovary
- Pregnancy
- Oral contraceptives
- Infusion of prothrombin complex concentrates
- Behçet disease
- Buerger disease
- Mondor disease

Commonly Associated Conditions

DVT: Superficial and deep vein thromboses (DVTs) can occur together from direct extension or noncontiguous findings.
- Incidence: Coexisting conditions 15% of time (1)[C]
- Both more likely in a hypercoagulable state
- Lower extremity superficial thrombophlebitis of great saphenous vein thought to be associated with DVTs (especially above knee) (1)[C]
Varicose veins
Systemic diseases such as pancreatic or other abdominal cancers
Hypercoagulable states such as Factor V Leiden, prothrombin gene mutation, antithrombin III (AT-III), protein C and protein S deficiencies
Surgery
Trauma, burns
Obesity, pregnancy
Thromboangiitis obliterans

Diagnosis

Pre Hospital

Treat initially with support stockings, elevation, and OTC analgesics, such as acetaminophen, or NSAIDs, such as ibuprofen.

History

Swelling over affected vein: May feel firm and “cordlike”
Redness and warmth of affected vein and area
Pain and tenderness to palpation

Physical Exam

Swelling, tenderness, mild erythema along the course of the affected vein(s); palpable “cord”
May look like cellulitis or erythema nodosa
Fever in 70% of patients
Warmth, significant erythema, tenderness, or lymphangiitis in 32%
Signs of systemic sepsis in 84% in suppurative thrombophlebitis (hypotension, tachycardia, shallow respirations, altered mental status, multiorgan failure)

Diagnostic Tests & Interpretation

Lab

CBC
Blood culture
Coagulation assay and special tests (eg, Factor V Leiden) may be indicated.
Other tests:
- Doppler or duplex US
- Venography
- Septic:
  - Bacteremia in 80–90%
  - Culture of IV fluid bag and tip
  - Leukocytosis
- Aseptic:
  - Acute-phase reactant
  - Patients with single episode of superficial thrombophlebitis do not require hypercoagulable screening. Screen for recurrent cases without known risk factors (2)[C].
    - Factor levels
    - Protein C and S
    - Thrombin activity
    - Platelet function test
Doppler or duplex US
Venography
Septic:
- Bacteremia in 80–90%
- Culture of IV fluid bag and tip
- Leukocytosis
Aseptic:
- Acute-phase reactant
- Patients with single episode of superficial thrombophlebitis do not require hypercoagulable screening. Screen for recurrent cases without known risk factors (2)[C].
  - Factor levels
  - Protein C and S
  - Thrombin activity
  - Platelet function test
Drugs that may alter lab results: In sepsis, broad-spectrum antibiotics
Disorders that may alter lab results: N/A

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Imaging

US of veins reveals an increase in the diameter of the lumen (can detect extension of thrombus but less useful in regions deep to the clavicle or mandible).
- Upper extremity superficial thrombophlebitis and saphenous thrombophlebitis below the knee do not require imaging in absence of risk factors for DVT (2)[C].
- Saphenous thrombophlebitis above the knee is more likely to progress to DVT and requires diagnostic US and follow-up US in 3–7 days (2)[C].
Chest x-ray: Multiple peripheral densities or a pleural effusion consistent with pulmonary embolism, abscess, or empyema
Bone and gallium scan: For associated subperiosteal abscess in septic thrombophlebitis
High-resolution CT scan with contrast material: Most useful for jugular or vena caval septic thrombophlebitis
Venography (more invasive than above)
Evaluation of complications (DVT and others)

Diagnostic Procedures/Surgery

Leukocyte imaging
Skin biopsy helpful in recurrent and migratory types as well as unclear cases

Pathological Findings

The affected vein is enlarged, tortuous, and thickened.
Associated perivascular suppuration and/or hemorrhage
Vein lumen may contain pus and thrombus.
Endothelial damage, fibrinoid necrosis, and thickening of the vein wall

Differential Diagnosis

Cellulitis
Erythema nodosa
Cutaneous polyarteritis nodosa
Sarcoid granuloma
Kaposi sarcoma
Hyperalgesic pseudothrombophlebitis
Panniculitis
Insect bite

Treatment

Septic: Inpatient
Aseptic: Outpatient

Medication

First Line

Septic:
- Initially, antistaphylococcal agent (vancomycin 30 mg/kg/day in 2 equally divided doses) plus an aminoglycoside (eg, gentamicin 1.7–2.0 mg/kg IV as a loading dose, followed by 1.5 mg/kg per renal function). If MSSA, change vancomycin to oxacillin 2 g IV q4h (3)[C].
- Duration of therapy is empirical.
- If due to Candida albicans, consider a short course of amphotericin B, ∼200 mg cumulative dose
- If osteomyelitis documented, antibiotic therapy for at least 6 wks
Aseptic:
- NSAIDs for upper extremity and below-the-knee clots without DVT risk factors
- Systemic LMWH or unfractionated heparin ×4 wks suggested for all above-the-knee superficial or large leg thromboses (4)[B],(5)[A]
- Oral anticoagulant warfarin with bridging as alternative (4)[C]
Antithrombin III and heparin cofactor II deficiency:
- IV heparin
- Antithrombin III concentrate
- Prophylaxis: Warfarin
Proteins C and S deficiency: Long-term warfarin, lower dose, no loading
Disorder of tissue plasminogen activator:
- Phenformin and ethylestrenol
- Stanozolol and phenformin
- Stanozolol alone
- Ethylestrenol alone

Second Line

Factor XII deficiency: Streptokinase or alteplase [tissue plasminogen activator (tPA)]
Behçet: Oral anticoagulants plus cyclosporine
Thromboangiitis obliterans: Corticosteroid, antiplatelets, and vasodilating drugs

Additional Treatment

General Measures

Heat application
Extremity elevation
Compression stockings
Continue ambulation: Bed rest is counterproductive. Patients tend to do better with early and continued mobilization (6)[C].
If occurs in setting of IV catheter, remove the catheter.

Referral

In high-risk patients (ie, patients with varicosities and a history of superficial thrombophlebitis), referral to a surgeon may be indicated. Vein stripping, phlebectomy, or sclerotherapy may be required to prevent further episodes.

Additional Therapies

Treatment with a therapeutic or prophylactic dose of LMWH or an NSAID reduces the incidence of SVT extension or recurrence but not the incidence of venous thromboembolic disease (7)[B].
An intermediate dose of LMWH for a month plus use of elastic compression stockings may be the best preventive approach, although more studies are needed (5)[A].

Surgery/Other Procedures

Septic:
- Surgery is always necessary in peripheral thrombophlebitis.
- If central vein is involved, surgical resection may not be possible.
- If septic thrombophlebitis is suspected, exploratory surgery should be performed (3)[C].
- Excision of the involved vein segment and all involved tributaries
- Excision from ankle to groin may be required in some burn patients.
- If systemic symptoms persist after vein excision, reexploration is necessary with removal of all involved veins.
- Drainage of contiguous abscesses
- Remove all cannulas.
Aseptic:
- Mondor disease: Consider surgical transection of the phlebitic cord.
- Management of underlying conditions

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Ongoing Care

Follow-Up Recommendations

Activity

Patient Monitoring

Septic:
- Routine WBC count and differential and culture
- Repeat culture from the phlebitic vein
Aseptic:
- For above-the-knee clots of the great saphenous vein, monitor with US after 3–7 days to exclude progression (1).
- Clinical follow-up to rule out secondary complications and improvement
- Repeat of blood studies for fibrinolytic system, platelets, and factors

Diet

No restrictions

Patient Education

Avoid trauma.
Be alert to change in skin color.
Be alert to tenderness over extremities.

Prognosis

Septic: High mortality (50%) if untreated
Aseptic:
- Usually benign course: Recovery in 7–10 days
- Antithrombin III and heparin cofactor deficiency: Recurrence rate is 60%.
- Proteins C and S: Recurrence rate is 70%.
- Prognosis depends on development of DVT and early detection of complications.
- Aseptic thrombophlebitis can be isolated, recurrent, or migratory.

Complications

Complications of superficial thrombophlebitis are relatively rare. Risk of embolism is uncommon compared with DVT.
Septic:
- Systemic sepsis, bacteremia (84%)
- Septic pulmonary emboli (44%)
- Metastatic abscess formation
- Gangrene
- Pneumonia (44%)
- Subperiosteal abscess of adjacent long bones in children
Aseptic:
- DVT
- Thromboembolic phenomena
Treatment/prevention of complications:
- Dysfibrinogenemia:
  - Acute attack: Anticoagulation
  - Prophylaxis: Stanozolol
- Abnormal plasminogen and plasminogenemia:
  - Acute attack: Anticoagulation
  - Prophylaxis: Warfarin
- Factor XII deficiency: Standard therapy
- Lupus anticardiolipin: Prophylaxis: Warfarin
- Trousseau syndrome: Heparin
- For pregnancy: Heparin
- Behçet disease:
  - Phenformin
  - Ethylestrenol
  - Stanozolol
- Thromboangiitis obliterans:
  - Stop smoking
  - Pentoxifylline
Contraindications: Refer to manufacturers' literature.
Precautions: Refer to manufacturers' literature.
Significant possible interactions: Refer to manufacturers' literature.

References

1. Decousus H, Epinat M, Guillot K, et al. Superficial vein thrombosis: risk factors, diagnosis, and treatment. Curr Opin Pulm Med. 2003;9:393–397.

2. Fernandez L. Superficial phlebitis. In: UpToDate, Sarkar R, Ed. UpToDate, Waltham, MA, 2009.

3. Spelman D. Suppurative (septic) thrombophlebitis. In: UpToDate, Sexton DJ, Ed. UpToDate, Waltham, MA, 2009.

4. Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:454S–545S.

5. Di Nisio M, Wichers IM, Middeldorp S. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev. 2007;CD004982.

6. Cesarone MR, Belcaro G, Agus G, et al. Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document. Angiology. 2007;58(Suppl 1):7S–14S; discussion 14S–15S.

7. Wichers IM, Di Nisio M, Büller HR, et al. Treatment of superficial vein thrombosis to prevent deep vein thrombosis and pulmonary embolism: a systematic review. Haematologica. 2005;90:672–677.

Additional Reading

Mandell GL, ed. Principles and practice of infectious diseases. 4th Ed. New York: Churchill Livingstone, 1995.

Samlaskie CP, James WD. Superficial thrombophlebitis I. Primary hypercoagulable states. J Am Acad Dermatol 1990;22:975–989.

Samlaskie CP, James WD. Superficial thrombophlebitis II. Secondary hypercoagulable states. J Am Acad Dermato. 1990;23:1–18.

Superficial Thrombophlebitis Treated By Enoxaparin Study Group. A pilot randomized double-blind comparison of a low-molecular-weight heparin, a nonsteroidal anti-inflammatory agent, and placebo in the treatment of superficial vein thrombosis. Arch Intern Med. 2003;163:1657–1663.