II. Epidemiology

  1. Deep Vein Thrombosis (DVT) represents 66% of Venous Thromboembolism (VTE)
    1. Pulmonary Embolism (PE) represents the remaining 33% of VTE
    2. Pulmonary Embolism accompanies proximal DVT in 40% of cases
    3. Deep Vein Thrombosis is identified in 70% of those with Pulmonary Embolism
  2. Venous Thromboembolism
    1. General population: 0.2% (200 per 100,000 person years)
      1. Incidence 900,000 patients per year in U.S. (per CDC in 2023)
    2. Elderly: 1% Incidence
    3. Hospitalized patients: 15% Incidence
    4. VTE annual mortality in U.S.: estimated at 60,000 to 100,000 per year

III. Pathophysiology

  1. VTE is caused by at least one of three dysfunctions (Virchow's Triad)
    1. Hypercoagulability
    2. Blood Flow alterations
    3. Endothelial injury or dysfunction

IV. Risk Factors

  1. See Deep Vein Thrombosis Risk Factors (includes Recurrent Thromboembolism Risks)
  2. See Thrombophilia
  3. May Turner Syndrome
    1. Compressed right iliac common artery (RICA) results in ileofemoral DVT
    2. Arterial variants of RICA predispose to compression
    3. Resulting RICA pressure against lumbar bony Vertebrae resulting in bony spur formation
    4. Spurs and RICA compress iliac veins, resulting in DVT (esp. Left ileofemoral DVT)
    5. More common in women (RR 2)
    6. Responsible for 2 to 5% of DVTs (esp. females in their teens and twenties)

V. History

  1. Deep Vein Thrombosis Related
    1. Recent Surgery (esp. in the last 3 months, and esp. orthopedic surgery)
    2. Recent prolonged travel (esp. in the last 2 weeks, and esp. >10,000 km or 6200 miles)
    3. Prolonged sitting >3 to 4.5 hours at a time
    4. Hypercoagulable State or Thrombophilia (personal or Family History)
    5. Congestive Heart Failure
    6. General Immobility
    7. Malignancy
    8. Current or recent pregnancy
    9. Tobacco Abuse
    10. Hormonal therapy (esp. Oral Contraceptives)
  2. Pulmonary Embolism Related
    1. Chest Pain
    2. Shortness of Breath
  3. Other cause related history
    1. Fever
    2. Recent Trauma
    3. Recent open wounds
    4. Spreading erythema

VI. Exam

  1. See Localized Edema
  2. See Brief Musculoskeletal Exam
  3. Careful exam to differentiate causes of Localized Edema (and associated erythema and pain)
  4. Complete extremity neurovascular exam with comparision to opposite side

VII. Signs

  1. Unilateral extremity edema
    1. Bilateral DVT occurs in up to 7% of cases
  2. Associated affected extremity findings (variable)
    1. Erythema
    2. Warmth
    3. Extremity Pain
  3. Clinical exam is unreliable for excluding DVT
    1. Homans' Sign (no predictive value)
      1. Homans' Sign: Relaxed foot abnormally plantar flexed
      2. Pseudo-Homans': Pain on passive dorsiflexion of foot
    2. Other unreliable signs
      1. Tenderness
      2. Distal extremity edema
      3. Palpable cord
  4. Significant DVT related extremity edema complications
    1. Phlegmasia Alba Dolens
      1. Pale white, severely edematous extremity (milk leg) with patent collateral veins
    2. Phlegmasia Cerulea Dolens
      1. Cyanotic or blue, severely edematous extremity (copper leg) with obstructed collateral veins

VIII. Differential Diagnosis

  1. See Localized Extremity Swelling
  2. Extremity Trauma
  3. Cellulitis
  4. Peripheral Arterial Disease
  5. Baker's Cyst (Pseudo-thrombosis)
  6. Superficial Thrombophlebitis
  7. Fat Embolism
    1. Complicates 0.5 to 2% of long bone Fractures
    2. Classic triad presentation is Orthopedic Trauma with Petechiae, Dyspnea and Altered Mental Status

IX. Diagnosis

  1. Images
    1. deepVeins.jpg
  2. Precautions
    1. See DVT in Pregnancy
    2. Exercise caution in pregnancy
      1. Pregnancy is higher risk of pelvic DVT (which is higher risk of PE and more difficult to detect)
  3. Step 1: Assess DVT Probability
    1. See Wells Clinical Prediction Rule for DVT
    2. If moderate to high probability, goto step 3
    3. Low probability Wells score does NOT exclude DVT (risk is still up to 5%)
  4. Step 2: Low Probability for DVT
    1. Obtain D-Dimer
    2. See D-Dimer for Discriminatory values (typically normal D-Dimer <=0.5 in age <50 years old)
    3. Negative D-Dimer: Excludes DVT in a low probability patient
      1. However, D-Dimer Test Sensitivity is 95%, and will miss 5% of DVTs
    4. Positive D-Dimer: Lower Extremity DopplerUltrasound
      1. Negative Ultrasound
        1. Excludes DVT
      2. Positive Ultrasound
        1. Treat as DVT
  5. Step 3: Moderate to high Probability for DVT
    1. Obtain Lower Extremity DopplerUltrasound (Test Sensitivity approaches 95%)
    2. Negative Compression Ultrasound: Obtain D-Dimer
      1. Negative D-Dimer
        1. Excludes DVT
      2. Positive D-Dimer
        1. Repeat Compression Ultrasound in one week or obtain CTV (venography) for pelvic DVT
    3. Positive Compression Ultrasound
      1. Treat as DVT
  6. References
    1. Bockenstedt (2003) N Engl J Med 349:1203-4 [PubMed]

X. Associated Conditions

  1. See Thrombophilia
  2. Idiopathic DVT associated with undiagnosed malignancy

XI. Evaluation: Unprovoked Venous Thromboembolism

  1. Thrombophilia
    1. See Thrombophilia for testing indications
    2. Consider directed screening in unprovoked VTE when diagnosis impacts management
  2. Malignancy
    1. Associated with a higher VTE recurrence rate (esp. brain, myeloproliferative, ovarian, lung and non-rectal GI cancer)
    2. Present in 20% of patients with VTE
      1. Relative Risk of malignancy diagnosis in 2 years: 3.0
        1. Oudega (2006) Brit J Gen Pract 56:693-6 [PubMed]
      2. Prevalence of occult malignancy in unprovoked VTE: 3.9%
        1. Carrier (2015) N Engl J Med 373(8): 697-704 [PubMed]
    3. Perform age and gender appropriate routine malignancy screening
      1. No other occult malignancy testing recommended (unless dictated by signs and symptoms)
      2. Atypical location (e.g. splenic or cerebral vein) may warrant additional testing
      3. Recurrence despite Anticoagulation, Family History and weight loss may also prompt evaluation

XII. Management: General

  1. See DVT in Pregnancy
  2. See Pulmonary Embolism Management
    1. Anticoagulation protocols are the same for DVT and PE
  3. Consider Thrombophilia work-up
    1. See Thrombophilia
    2. Reserve blood for tests prior to Anticoagulation
  4. Anticoagulation Protocol
    1. Anticoagulation in Thromboembolism
  5. Disposition
    1. Hospitalization and Heparin for high risk patients
    2. Consider home management with LMWH (see below)
  6. Local measures
    1. Early ambulation
      1. Replaces prior recommendations to minimize activity for first few days
    2. Elevate affected limb to reduce swelling
    3. Apply heat to affected limb
    4. Graded elastic Compression Stockings (20-30 mmHg)
      1. Reduce risk of Postphlebitic Syndrome (Postthrombotic Syndrome)
      2. Kolbach (2004) Cochrane Database Syst Rev (1): CD004174 [PubMed]
  7. Superficial Venous Thrombosis Anticoagulation indications
    1. See Superficial Venous Thrombosis
    2. Proximal superficial clot (upper thigh) especially within 5 cm of deep system
    3. Clot >7 cm long in leg
    4. Lack of improvement after 1 week
    5. Hypercoagulable state

XIII. Management: Distal DVT (Calf-vein DVT)

  1. Option 1: Anticoagulation (standard strategy since 2001)
    1. Anticoagulation recommended for 6 to 12 weeks
      1. Initiate with LMWH and then to oral Warfarin (or other Anticoagulant - see above)
    2. Justification (based on risk of untreated calf DVT complications)
      1. Risk of propogation to proximal DVT is 5-20% (NNT 16)
      2. Recurs in 30% of untreated patients
      3. Post-Thrombotic Syndrome occurs in 20% if untreated
      4. Pinede (2001) Circulation 103:2453-60 [PubMed]
      5. Utter (2016) JAMA Surg 151(9): e161770 +PMID:27437827 [PubMed]
  2. Option 2: 2015 Chest Guidelines recommend serial Ultrasound instead of Anticoagulation
    1. Assumes lower risk patient
      1. Asymptomatic
      2. No cancer history or other underlying Coagulopathy
      3. DVT not unprovoked and not recurrent
    2. Preferred strategy if Anticoagulation contraindicated or increased bleeding risk
    3. Safe even in symptomatic patients, with similar outcomes to Anticoagulation, but without the 4% bleeding risk
      1. Righini (2016) Lancet Hematol 3(12): e556-62 +PMID: 27836513 [PubMed]
    4. Repeat Doppler Ultrasound twice weekly for 2 weeks
    5. Monitor for extension of distal DVT to proximal DVT
    6. Kearon (2016) Chest 149(2): 315-52 +PMID:26867832 [PubMed]

XIV. Management: Anticoagulation

XV. Management: Home Deep Vein Thrombosis Protocol

  1. Criteria for home management
    1. No massive Deep Vein Thrombosis
      1. No entire Leg Swelling, acrocyanosis or ischemia
      2. No DVT extension into iliofemoral vein or IVC
    2. No symptomatic Pulmonary Embolism
      1. Oxygen Saturation >95% on room air
    3. No significant bleeding risks on Anticoagulants
      1. Active bleeding or bleeding in last 4 weeks
      2. Recent surgery or Trauma
      3. Platelet Count <70, INR >1.4 or PTT >40 sec
      4. Metastatic disease involving liver or brain
    4. No significant comorbidities
      1. No severe liver or Kidney disease
      2. Impaired cognition or mobility
      3. Pain requiring ParenteralNarcotics
    5. References
      1. Douketis (2005) Can Fam Physician 51:217-23 [PubMed]
  2. Efficacy
    1. Safe and effective management of proximal DVT
    2. Spyropoulos (2002) Chest 122:108-14 [PubMed]
  3. Review Contraindications
    1. Use only in otherwise low risk patients
    2. See Low Molecular Weight Heparin for contraindication
  4. Patient Education
    1. Demonstrate self-administered Subcutaneous Injections
    2. Review sterile technique
    3. Review risks of bleeding and infection
    4. Emphasize precautions against Trauma
  5. Consider home health referral
  6. Anticoagulation
    1. See Anticoagulation in Thromboembolism

XVI. Management: Intervention Radiology directed Thrombolysis (with benefit)

  1. Ileofemoral DVT (typically within last 14 days)
    1. High risk of comorbidity
      1. Post-Thrombotic Syndrome: >50%
      2. Venous Claudication at 5 years in nearly half of patients
    2. Efficacy data (some studies question longterm benefit)
      1. Normal vein after Catheter Thrombolysis: 45% (contrast with 0% after Heparin alone)
      2. Decreases risk of long term Venous Insufficiency, Post-Phlebitic Syndrome, stasis ulcers
      3. Best outcome if performed early (within 2 weeks)
      4. Poor efficacy if prior Deep Vein Thrombosis
    3. References
      1. (2009) J Thromb Haemost 7:1268-75 [PubMed]
  2. Other indications
    1. Massive proximal extremity DVT with severe symptoms or Limb Threatening Ischemia

XVII. Complications

  1. Pulmonary Embolism (PE)
    1. PE is an increased risk in the first 2 weeks after DVT diagnosis and Anticoagulation start
  2. Post-Thrombotic Syndrome (Postphlebitic Syndrome)
    1. Affects up to 50% of DVT patients, with chronic symptomatic Venous Insufficiency
    2. Reduced with below knee graded Compression Stockings
      1. Prandoni (2004) Ann Intern Med 141:249-56 [PubMed]
    3. Encourage 30 minute walk per day
      1. Kahn (2011) CMAJ 183(1):37-44 +PMID:21098066 [PubMed]
  3. Breakthrough Venous Thromboembolism
    1. See Prognosis below
    2. Occurs in 2 to 3% of VTE patients on Anticoagulation for 6 months
    3. Considered Breakthrough VTE if occurs at least 2 weeks after consistent Anticoagulation initiated
  4. Phlegmasia (Milk Leg)
    1. Rare, high risk complications (mortality approaches 20 to 50%)
    2. Phlegmasia Alba Dolens
      1. Painful, white leg following ileo-femoral deep vein obstruction with patent superficial collateral
    3. Phegmasia Cerulea Dolens
      1. Painful, cyanotic, edematous leg following combined ileo-femoral deep AND superficial vein obstruction
      2. Venous Gangrene (capillary obstruction) results if not promptly managed

XVIII. Prognosis

  1. Overall mortality is increased in DVT patients
    1. Month 1: Mortality 3 to 6%
    2. Year 1 Mortality 13%
    3. Year 10 Mortality 42%
    4. Year 30: Mortality 68%
    5. Sogaard (2014) Circulation 130(10): 829-36 [PubMed]
    6. Naess (2007) J Thromb Haemost 5(4): 692-9 [PubMed]
  2. Recurrence when not on Anticoagulation
    1. See Thromboembolism Risk Factors
    2. Provoked VTE with transient risk factors: 3.3% recurrence rate in first year
    3. Unprovoked VTE: 10.3% recurrence rate in first year (30% in first 10 years)
    4. Proximal DVT has a 4 fold higher risk of recurrence than distal DVT
    5. Central Pulmonary Embolism has higher risk of recurrence than peripheral PE
    6. Elevated D-Dimer 3 weeks after stopping Anticoagulation is associated with higher risk of VTE recurrence
      1. Eichinger (2003) JAMA 290(8): 1071-4 [PubMed]

XX. Resources

  1. CDC: Venous Thromboembolism
    1. https://www.cdc.gov/ncbddd/dvt/data.html

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