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
- For those with coagulopathy:
- 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.