Superficial Thrombophlebitis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

• Superficial thrombophlebitis is an inflammatory condition of the veins 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

Geriatric Considerations

Septic thrombophlebitis is more common; prognosis is poorer.

Pediatric Considerations

Subperiosteal abscesses of adjacent long bone may complicate the disorder.

Pregnancy Considerations

• Associated with increased risk of aseptic superficial thrombophlebitis
• Warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated.

Epidemiology

• Predominant age:
  • Septic: More common in childhood
  • Aseptic primary hypercoagulable state:
    • Antithrombin III and heparin cofactor II deficiency: Neonatal period, but 1st episode usually at age 20–30 years
    • Proteins C and S: <30 years of age
  • Aseptic secondary hypercoagulable state:
    • Mondor disease: Women, ages 21–55 years
    • Thromboangiitis obliterans onset: Ages 20–50 years
• Predominant sex:
  • Suppurative: Male = Female.
  • Aseptic:
    • Mondor: Female > Male (2:1)
    • Thromboangiitis obliterans: Female > Male (1–19% of clinical cases)

Incidence

• Septic:
  • Up to 10% of all nosocomial infections
  • Incidence of catheter-related thrombophlebitis is 88/100,000 persons.
  • Develops in 4–8% if cutdown is performed
• Aseptic primary hypercoagulable state: Antithrombin III and heparin cofactor II deficiency incidence is 50/100,000 persons.
• Aseptic secondary hypercoagulable state:
  • Trousseau syndrome (migratory venous thrombosis associated with occult malignancy)
  • Trousseau syndrome incidence in malignancy is 5–15%.
  • Trousseau syndrome incidence in pancreatic carcinoma is 50%.
  • In pregnancy, 49-fold increased incidence of phlebitis
  • Superficial migratory thrombophlebitis in 27% of patients with thromboangiitis obliterans

Prevalence

• Superficial thrombophlebitis is common.
• One-third of patients in a medical ICU develop thrombophlebitis that eventually progresses to the deep veins.

Risk Factors

• Nonspecific:
  • Immobilization
  • Obesity
  • Advanced age
  • Postoperative states
• Septic:
  • IV catheter (68% of cannulas have been left in place for 2 days)
  • Incidence is 40× higher with plastic cannulas (8%) than with steel or scalp cannulas (0.2%).
  • Lower extremity IV catheter
  • Cutdowns
  • Cancer, debilitating diseases
  • Steroid
  • Thrombosis
  • Dermal infection
  • Burned patients
  • IV antibiotics
  • AIDS
  • Varicose veins
• Antithrombin II and heparin cofactor II deficiency:
  • Pregnancy
  • Oral contraceptives
  • Surgery, trauma, infection
• In pregnancy:
  • Increased age
  • Hypertension
  • Eclampsia
  • Increased parity
• Thromboangiitis obliterans: Persistent smoking
• Mondor disease:
  • Breast abscess
  • Antecedent breast surgery
  • Breast augmentation
  • Reduction mammoplasty
• Superficial thrombophlebitis may occur spontaneously or as a complication of medical or surgical interventions.

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

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 h
• Antibacterial ointment in cutdown

Pathophysiology

• Microscopic thrombosis is a normal part of the dynamic balance of hemostasis.
• In the absence of a triggering event, neither venous stasis nor abnormal coagulability alone causes clinically important thrombosis.
• Vascular endothelial injury does reliably cause thrombus formation. The initiating injury triggers an inflammatory response that results in immediate platelet adhesion at the site of injury.
• Platelet aggregation owing to thromboxane A2 is inhibited reversibly by NSAIDs and irreversibly by aspirin, but thrombin-mediated platelet aggregation is unaffected by aspirin and NSAIDs.

Etiology

• Septic:
  • Staphylococcus aureus in 65–78%
  • Enterobacteriaceae, especially Klebsiella
  • Multiple organisms in 14%
  • Anaerobic isolate rare
  • Candida sp.
  • Cytomegalovirus (CMV) 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): Most commonly seen in metastatic mucin or adenocarcinomas of the GI tract (pancreas, stomach, colon, and gallbladder), lung, prostate, and ovary
  • Pregnancy
  • Oral contraceptives
  • Infusion of prothrombin complex concentrates
  • Behçet disease
  • Buerger disease
  • Mondor disease

Diagnosis

History

Pain along the course of a vein

Physical Exam

• Swelling, tenderness, redness along the course of a vein or veins
• May look like cellulitis or erythema nodosa
• Fever in 70% of patients
• Warmth, erythema, tenderness, or lymphangitis in 32%
• Sign of systemic sepsis in 84% of suppurative

Diagnostic Tests & Interpretation

Lab

• If septic concern:
  • Blood cultures (bacteremia in 80–90%)
  • Culture of IV fluid bag
  • Complete blood count (CBC) demonstrates leukocytosis.
• Aseptic: Evaluation for coagulopathy if recurrent (e.g., protein C, protein S, lupus anticoagulant, anticardiolipin antibody, factor analysis)

Imaging

Septic and aseptic:

• None needed if below the knee and no risk factors for deep vein thrombosis (DVT)
• Evaluation of complications (DVT and others):
  • CXR: 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

Diagnostic Procedures/Surgery

Skin biopsy if not responding to therapy as expected

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
• Kaposi sarcoma
• Hyperalgesic pseudothrombophlebitis

Treatment

Medication

First Line

• Septic:
  • Initially: Semisynthetic penicillin (e.g., nafcillin 2 g IV q6h) plus an aminoglycoside (e.g., gentamicin, 1.0–1.7 mg/kg IV)
  • Duration of therapy is empirical.
  • If due to Candida albicans, consider a short course of amphotericin B, ∼200-mg cumulative dose
  • If osteomyelitis is documented, antibiotic therapy × 6 weeks at least
• Aseptic, general:
  • For those with coagulopathy:
    • NSAIDs
    • Removal of catheter, if placed
    • Oral anticoagulant warfarin
    • Systemic anticoagulant heparin
    • Low-molecular-weight heparin
  • Antithrombin III and heparin cofactor II deficiency: IV heparin
  • Antithrombin III concentrate: Prophylaxis: Warfarin, oxymetholone
• Proteins C and S: Long-term warfarin, lower dose, no loading
• Disorder of tissue plasminogen activator:
  • Phenformin and ethylestrenol
  • Stanozolol and phenformin
  • Stanozolol alone
  • Ethylestrenol alone
• 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 the manufacturer’s literature for each drug.
• Precautions: Refer to the manufacturer’s literature for each drug.
• Significant possible interactions: Refer to the manufacturer’s literature for each drug.

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

Surgery/Other Procedures

• Septic:
  • Excision of the involved vein segment and all involved tributaries if failed conservative treatment
  • 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: Management of underlying conditions

In-Patient Considerations

Initial Stabilization

• Septic: Inpatient
• Aseptic: Outpatient

Ongoing Care

Follow-Up Recommendations

Bed rest

Patient Monitoring

• Septic:
  • Routine white blood cell (WBC) count and differential and culture
  • Repeat culture from the phlebitic vein
• Aseptic:
  • Clinical follow-up to rule out secondary complications
  • 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 60%
  • Proteins C and S: Recurrence rate 70%
  • Prognosis depends on development of DVT and early detection of complications.
  • Aseptic thrombophlebitis can be isolated, recurrent, or migratory.

Complications

• Septic: Systemic sepsis, bacteremia (84%), septic pulmonary emboli (44%), metastatic abscess formation, pneumonia (44%), subperiosteal abscess of adjacent long bones in children
• Aseptic: DVT, thromboembolic phenomena

Additional Reading

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

2. Gillet JL, French P, Hanss M, et al. Predictive value of D-dimer assay in superficial thrombophlebitis of the lower limbs. J Mal Vasc. 2007.

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

4. Samlaska CP, James WD. Superficial thrombophlebitis. I. Primary hypercoagulable states. J Am Acad Dermatol. 1990;22:975–89.

See Also (Topic, Algorithm, Electronic Media Element)

Thrombosis, Deep Vein

Codes

ICD9

• 451.0 Phlebitis and thrombophlebitis of superficial vessels of lower extremities
• 451.9 Phlebitis and thrombophlebitis of unspecified site
• 451.82 Phlebitis and thrombophlebitis of superficial veins of upper extremities
• 289.81 Primary hypercoagulable state
• 289.82 Secondary hypercoagulable state

Snomed

• 2477008 superficial thrombophlebitis (disorder)
• 40283005 thrombophlebitis of superficial veins of lower extremity (disorder)
• 95451004 thrombophlebitis of superficial veins of upper extremities (disorder)
• 76612001 hypercoagulability state (finding)

Clinical Pearls

• The disease can develop while on a plane.
• The best modality to prevent the disease during air travel is to exercise and drink a lot of water.