> Table of Contents > Deep Vein Thrombophlebitis
Deep Vein Thrombophlebitis
Denisse V. Tafur, MD
Alfonso Tafur, MD, MS, RPVI
image BASICS
DESCRIPTION
  • Development of blood clot within the deep veins, usually accompanied by inflammation of the vessel wall
  • Major clinical consequences are embolization (usually to the lung) and postphlebitic syndrome.
  • System(s) affected: cardiovascular
EPIDEMIOLOGY
  • Age and gender adjusted incidence of venous thromboembolism (VTE) is 100 times higher in the hospital than in the community. Almost half of all VTEs occur either during or soon after discharge from a hospital stay or surgery.
  • Of patients with VTE, 1/3 die within 30 days, 20% will have sudden death due to pulmonary embolism (PE). The 28-day DVT fatality rate is 9%.
Incidence
  • In the United States, VTE occurs for the first time in 100/100,000 persons/year.
  • ˜2/3 of the new VTE cases are DVT alone.
  • Higher incidence among Caucasians and African Americans relative to Hispanics and Asians
  • Complicates ˜1/1,000 pregnancies
Prevalence
Variable; depends on medical condition or procedure
  • 22-52% of the patients with PE have DVT.
  • 25% of patients with superficial venous thrombosis (1)[B]
  • Present in 11% of patients with acquired brain injury entering to neurorehabilitation
ETIOLOGY AND PATHOPHYSIOLOGY
Factors involved may include venous stasis, endothelial injury, and abnormalities of coagulation.
Genetics
  • Factor V Leiden is found in 5% of the population and in 20% of all VTE events. It is the most common thrombophilia. Homozygosity is found in 1/5,000 persons. It increases the risk of VTE 3- to 8-fold in heterozygous carriers and 50- to 80-fold in homozygous.
  • Prothrombin 20210A is found in 3% of Caucasians. Increases the risk of thrombosis ˜3-fold.
RISK FACTORS
  • Acquired: age, previous thrombosis, immobilization, major surgery, orthopedic surgery, malignancy, oral contraceptives, hormonal replacement therapy, antiphospholipid syndrome, polycythemia vera, paroxysmal nocturnal hemoglobinuria, pregnancy/puerperium, diabetes who developed VTE
  • Inherited: antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden R506Q, prothrombin G20210A, dysfibrinogenemia
  • Mixed/unknown: hyperhomocysteinemia, high levels of factor VIII, high levels of thrombin activatable fibrinolysis inhibitor (TAFI), high levels of factor XI
GENERAL PREVENTION
  • Mechanical thromboprophylaxis is recommended in patients with high bleeding risk and as adjunct to anticoagulant-based thromboprophylaxis.
  • Compression stockings have conflicting data on postthrombotic syndrome prevention (2)[B].
  • Risk stratification of hospitalized patients using standardized scores is recommended (i.e., Caprini score).
  • For acutely ill and for critically ill hospitalized patients at increased risk of thrombosis, low-molecular-weight heparin [LMWH], low-dose unfractionated heparin [LDUH], or fondaparinux are recommended (3)[C].
  • Rivaroxaban and apixaban are approved in United States for surgical DVT prevention.
  • For most patients, prolonged secondary prophylaxis is not recommended.
image DIAGNOSIS
Modified Wells criteria
  • Active cancer +1 point. Calf swelling >3 +1 point. Collateral superficial veins +1 point. Pitting edema +1 point. Previous documented DVT +1 point. Swelling of entire leg +1 point. Localized pain along distribution of deep venous system +1 point. Paralysis, paresis, or recent cast immobilization of lower extremities +1 point. Recently bedridden >3 days or major surgery requiring regional or general anesthetic in past 4 weeks +1 point. Alternative diagnosis at least as likely −2 points
  • Interpretation: Score 0 to 1 DVT unlikely. Score ≥2: moderate to high probability.
PHYSICAL EXAM
  • Physical exam is only 30% accurate for DVT.
  • Resistance to dorsiflexion of the foot (Homan sign) is unreliable.
  • Swelling of collateral veins. Massive edema with cyanosis is a medical emergency (phlegmasia cerulea dolens, rare).
  • Thoracic outlet maneuvers in upper extremity DVT
  • Attention to signs of possible malignancy
DIFFERENTIAL DIAGNOSIS
Cellulitis, fracture, ruptured synovial cyst (Baker cyst), lymphedema, muscle strain/tear, extrinsic compression of vein (e.g., by tumor/enlarged lymph nodes), compartment syndrome, localized allergic reaction
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • D-dimer (sensitive but not specific; has a high negative predictive value [NPV])
  • Patients with a prior DVT and those with malignancy have a high rate of VTE, which decreases the NPV of Wells prediction rule (4).
  • CBC, platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT)/INR
  • In young patients with idiopathic/recurrent VTE, consider thrombophilia testing.
  • Compression ultrasound (CUS): noninvasive; sensitive and specific for popliteal, femoral thrombi but has poor ability to detect calf vein thrombi
  • Contrast venography: gold standard, is technically difficult, risk of morbidity
  • Impedance plethysmography: as accurate as duplex US, less operator dependent but poor at detecting calf vein thrombi; not widely available
  • MR venography: as accurate as contrast venography; may be useful for patients with contraindications to IV contrast
  • 125I-fibrinogen scan: detects only active clot formation; very good at detecting ongoing calf thrombi; takes 4 hours for results
  • In patients with suspected DVT, the choice of diagnostic test process should be guided by the assessment of the pretest probability.
    • Low pretest probability: D-dimer, proximal CUS
    • Moderate pretest probability: D-dimer, proximal CUS, whole leg US
    • High pretest probability: proximal CUS, whole leg US
    • If negative, no further testing is recommended.
    • If positive
      • Low pretest probability, then CUS
      • Moderate pretest probability, then proximal CUS/whole leg US
      • CUS: if positive, treat DVT; if negative
    • Low pretest probability, no further testing
    • Moderate pretest probability, repeat proximal CUS in 1 week
Follow-Up Tests & Special Considerations
Risk of an underlying malignancy is more likely if recurrent VTE, risk 3.2 (95% CI 2.0-4.8). Unprovoked VTE, 4.6 times higher (vs. secondary); upper extremity DVT, not catheter associated; odds ratio (OR) 1.8, abdominal DVT; OR 2.2, (5) bilateral lower extremity DVT, OR 2.1 (5)
image TREATMENT
MEDICATION
All proximal DVTs should receive treatment. Consider starting therapy even before confirmation in patients with high pretest probability.
First Line
  • Unfractionated heparin (UFH)
    • IV drip: initial dose of 80 U/kg or 5,000 U followed by continuous infusion of 18 U/kg/hr. Target an aPTT ratio >1.5. The aPTT prolongation should correspond to a 0.3 to 0.7 anti-Xa level.
    • SC UFH: monitored: 17,500 U or 250 U/kg BID with aPTT adjustment to an equivalent to 0.3 to 0.7 anti-Xa. Alternatively, fixed dose: 333 U/kg followed by BID dose 250 U/kg.
  • Enoxaparin (Lovenox): 1 mg/kg/dose SC q12h or 1.5 mg/kg/dose OD
  • Dalteparin (Fragmin): 200 U/kg SC q24h
  • Fondaparinux (Arixtra): 5 mg (body weight <50 kg), 7.5 mg (body weight = 50 to 100 kg), or 10 mg (body weight >100 kg) SC once daily
  • Rivaroxaban (Xarelto): 15 mg PO twice daily with food for the first 3 weeks.
  • Apixaban (Eliquis): 10 mg PO twice daily for 1 week followed by 2.5 to 5 mg PO twice daily
  • 2016 CHEST guidelines recommend using dabigatran, rivaroxaban, apixaban, or edoxaban instead of vitamin K antagonists for the first 3 months' treatment. Evidence to support these recommendations remains mixed. Because of cost and insurance coverage, implementation of these recommendations will be variable (http://journal.publications.chestnet.org/article.aspx?articleid=2479255).
  • P.257

  • Maintenance therapy
    • Warfarin (Coumadin): 5 mg/day for 3 days, then adjust to a target INR of 2 to 3; overlap with injectable anticoagulant for minimum of 5 days and two consecutive therapeutic INRs
    • Rivaroxaban (Xarelto): 20 mg PO once daily with food after the first 3 weeks
    • Apixaban (Eliquis): 2.5 to 5 mg PO twice daily after the first 1 week
    • Dabigatran (Pradaxa): 150 mg PO twice daily (CrCl >30 mL/min) after 5 to 10 days of parenteral anticoagulant
    • Edoxaban (Savaysa): 60 mg PO once daily following 5 to 10 days of initial therapy with a parenteral anticoagulant (30 mg If CrCl 15 to 50 mL/min or ≤60 kg)
  • Adverse effects
    • Heparin or LMWH: bleeding, edema, injection site irritation, skin eruptions, hematoma, thrombocytopenia
    • Fondaparinux: bleeding, injection site irritation, rash, fever, anemia
    • Warfarin: bleeding, skin necrosis, teratogenicity
    • Rivaroxaban: bleeding, anemia, rash, increase in transaminases
    • Dabigatran: bleeding, rash, edema
    • Edoxaban: bleeding, rash, anemia
  • Contraindications
    • Heparin or LMWH: bleeding, heparin hypersensitivity, heparin-induced thrombocytopenia (HIT), idiopathic thrombocytopenic purpura (ITP)
    • Fondaparinux: bleeding, thrombocytopenia
    • Warfarin: current bleeding, alcoholism, preeclampsia, pregnancy, surgery
Second Line
Heparin can be given by intermittent SC self-injection.
Pregnancy Considerations
  • Warfarin (Coumadin) is a teratogen; treat with full-dose heparin initially, followed by SC heparin starting at 15,000 U q12h.
  • Warfarin is safe with breastfeeding.
  • LMWH, dalteparin, fondaparinux, apixaban are pregnancy Category B.
  • Dabigatran, Edoxaban are pregnancy Category C.
ADDITIONAL THERAPIES
Edoxaban (recently FDA approved) after initial treatment with heparin is as effective as warfarin in preventing recurrences in patients with acute VTE and has less bleeding complications (6)[B].
SURGERY/OTHER PROCEDURES
  • In selected patients with proximal DVT (iliofemoral DVT, <2 weeks of symptoms, good functional status, >1 year of life expectancy), consider catheter-directed thrombolysis/open thrombectomy.
  • When anticoagulants have failed or are contraindicated, filtering devices are recommended in the acute setting.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Admission for respiratory distress, proximal VTE, candidate for thrombolysis, active bleeding, renal failure, phlegmasia cerulea dolens, history of HIT
Nursing
Limb elevation and multilayered compression.
Discharge Criteria
Medically stable and properly anticoagulated; overlap of anticoagulation and warfarin monitoring may be done as an outpatient.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Gradual resumption of normal activity, with avoidance of prolonged immobility
  • Duration of warfarin treatment after DVT
    • 3 months for treatment of a DVT secondary to a reversible risk factor
    • Patients with unprovoked DVT can be considered for prolonged secondary prophylaxis
      • In patients who have completed 3 months of anticoagulation after an unprovoked VTE, a positive D-dimer 1 month after discontinuation of therapy correlates with the risk of VTE recurrence (7)[A].
Patient Monitoring
  • Monitor platelet count while on heparin, LMWH, fondaparinux.
  • An anti-Xa activity level may help guide LMWH titration of therapy, but it is not usually needed.
  • Investigate significant bleeding (e.g., hematuria or GI hemorrhage) because anticoagulant therapy may unmask a preexisting lesion (e.g., cancer, peptic ulcer disease, or arteriovenous malformation).
PATIENT EDUCATION
  • Patients should wear compression stockings post-DVT.
  • Dietary habits should be discussed when warfarin is initiated to ensure that intake of vitamin K-rich foods is monitored.
PROGNOSIS
  • 20% of untreated proximal (e.g., above the calf) DVTs progress to pulmonary emboli, and 10-20% of those are fatal; with anticoagulant therapy, mortality is decreased 5- to 10-fold.
  • DVT confined to the infrapopliteal veins has a small risk of embolization but can propagate into the proximal system.
REFERENCES
1. Decousus H, Quéré I, Presles E, et al. Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study. Ann Intern Med. 2010;152(4):218-224.
2. Kahn S, Shapiro S, Wells P, et al. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet. 2014;383(9920):880-888.
3. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e152S-e184S.
4. Geersing GJ, Zuithoff NP, Kearon C, et al. Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. BMJ. 2014;348:g1340.
5. Tafur AJ, Kalsi H, Wysokinski WE, et al. The association of active cancer with venous thromboembolism location: a population-based study. Mayo Clin Proc. 2011;86(1):25-30.
6. Büller HR, Décousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013:369(15):1406-1415.
7. Palareti G, Cosmi B, Legnani C, et al. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med. 2006;355(17):1780-1789.
Additional Reading
&NA;
  • Agnelli G, Büller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Eng J Med. 2013;369(9):799-808.
  • Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Eng J Med. 2010;363(26):2499-2510.
  • Kyrle PA, Rosendaal FR, Eichinger S. Risk assessment for recurrent venous thrombosis. Lancet. 2010;376(9757):2032-2039.
  • Lyman GH, Khorana A, Kuderer N, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(17):2189-2204.
  • Prins MH, Lensing AW, Bauersachs R, et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11(1):21.
  • Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352.
See Also
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Antithrombin Deficiency; Factor V Leiden; Protein C Deficiency; Protein S Deficiency; Prothrombin 20210 (Mutation); Pulmonary Embolism
Codes
&NA;
ICD10
  • I80.209 Phlbts and thombophlb of unsp deep vessels of unsp low extrm
  • I80.299 Phlebitis and thombophlb of deep vessels of unsp low extrm
  • I80.10 Phlebitis and thrombophlebitis of unspecified femoral vein
Clinical Pearls
&NA;
  • Many cases are asymptomatic and are diagnosed after embolization.
  • Of the patients with superficial thrombophlebitis, 25% will have DVT at presentation.
  • Heparin and warfarin should overlap for a minimum of 5 days to achieve target INR.
  • The current American Society of Clinical Oncology guidelines acknowledge the value of primary prophylaxis in selected patients with active cancer receiving outpatient chemotherapy.