• Clinical science

Deep vein thrombosis (Phlebothrombosis)

Abstract

Deep vein thrombosis (DVT) is caused by the formation of a blood clot in a deep vein, typically of the calves. Thrombosis is often seen in people with a history of immobilization, obesity, (undetected) malignancy, or hereditary thrombophilia. Vascular endothelial damage, venous stasis, and hypercoagulability, known as Virchow's triad, are the main causative factors. Symptoms usually occur unilaterally and include swelling, tenderness, and redness or discoloration. In patients with dizziness, dyspnea, and fever, pulmonary embolism, which is a severe complication of DVT, should be suspected. The diagnostic test of choice is compression ultrasound to demonstrate the location and severity of the clot. An additional D-dimer test can mostly rule out thrombosis (or pulmonary embolism) if negative, whereas a positive test is nonspecific and may have various causes. Initial acute treatment of DVT consists of anticoagulation with heparin, and may also include thrombolysis or thrombectomy if thrombi are large or unresponsive to anticoagulation. Secondary prophylaxis is achieved with oral warfarin and supportive measures, such as regular exercise and use of compression stockings.

Etiology

Risk factors for deep vein thrombosis

  • History of DVT or PE (30-fold increased risk)
  • Immobilization (e.g., surgery, long-distance flights, trauma) (20-fold increased risk)
  • Age > 60 years
  • Malignancy
  • Hereditary thrombophilia (especially factor V Leiden)
  • Pregnancy, estrogen use (oral contraceptives)
  • Obesity
  • Smoking
  • Insufficient thrombosis prophylaxis, non-compliance with prophylaxis

References:[1][2]

Pathophysiology

Virchow's triad

Virchow's triad describes the main pathophysiological components of thrombus formation.

  1. Endothelial damage: inflammatory, traumatic
  2. Venous stasis: varicosis, external pressure on the extremity, immobilization, local application of heat
  3. Hypercoagulability: increased platelet adhesion, increased clotting tendency (thrombophilia)

Localization

  • Affects deep veins of the legs, thighs, or pelvis
  • More common in the left leg: compression of the left iliac vein through the right iliac artery
    • May-Thurner syndrome: left iliac vein is compressed between the right iliac artery and a lumbar vertebra (occurs in > 20% of adults)

References:[1][3][4][5]

Clinical features

  • Localized unilateral symptoms
    • Swelling, feeling of tightness or heaviness
    • Warmth, erythema, and possibly livid discoloration
    • Progressive tenderness, dull pain
      • Homan sign: calf pain on dorsal flexion of the foot
      • Meyer sign: compression of the calf causes pain
      • Payr sign: Plantar pain triggered by pressure on the medial foot sole
    • Distention of surface veins
    • Possibly palpable cord
  • General symptoms: fever
  • Possible signs of pulmonary embolism: dyspnea, chest pain, dizziness, weakness

References:[1][6]

Subtypes and variants

Phlegmasia cerulea dolens

  • Definition: : A severe form of phlebothrombosis, characterized by obstruction of all veins of one extremity with subsequent compression of arterial flow and high mortality.
  • Symptoms
    • Severe swelling, edema, and pain
    • Coldness, cyanosis, pulselessness
  • Treatment
    • Emergency surgery: venous thrombectomy, fasciotomy (amputation as last resort)
    • Fibrinolysis if surgery fails
  • Complications: shock, gangrene, acute renal failure (due to rhabdomyolysis)

Paget-Schroetter disease (upper extremity deep vein thrombosis)

References:[7][8]

Diagnostics

The management approach of suspected DVT is determined by the Well's score, and consists mainly of compression ultrasonography and elevated D-dimer levels.

Wells criteria for deep vein thrombosis

The score determines the probability of deep vein thrombosis, which has an effect on management. A different version may be used for determining the probability of pulmonary embolism (see Wells criteria for PE).

Criteria Score
Medical history Active cancer +1
Previously documented DVT +1
Immobilization Paralysis or recent (cast) immobilization of lower extremity +1
  • Recently bedridden (≥ 3 days) or
  • Major surgery (< 12 weeks)
+1
Clinical symptoms Localized tenderness along the deep venous system +1
Swelling of entire leg +1
Calf swelling ≥ 3 cm compared to asymptomatic calf +1
Unilateral pitting edema in symptomatic leg +1
Collateral (non-varicose) superficial veins present +1
Differential diagnosis Alternative diagnosis at least as likely as DVT -2
Interpretation
  • ≥ 2: DVT likely
  • ≤ 1: DVT unlikely

Compression ultrasonography with Doppler (test of choice)

  • Definition: Combination of ultrasonography to visualize the vein and doppler to assess blood flow abnormalities while the examiner applies pressure using the ultrasound probe
  • High sensitivity and specificity, but very operator dependent
  • Indications: suspected DVT in veins that can be compressed by the ultrasound probe (i.e., of the upper and lower limbs)
    • Especially sensitive assessment of popliteal and femoral vein
    • Duplex ultrasonography without compression is used to assess DVT in the iliac veins
  • Findings: non-compressibility of the obstructed vein, visible hyperechoic mass, absent/abnormal flow in Doppler imaging

D-dimer testing

  • High sensitivity (∼ 95%), low specificity (∼ 50%)
  • Normal test results rules out DVT
  • Elevated D-dimers alone are not proof of DVT

Further diagnostic tests

  • Venography: (angiography)
    • Most accurate assessment of calf veins and valvular competency
    • Indications: obese patients, severe edema, equivocal results in previous tests
  • CT scan: : suspected pulmonary embolism or underlying malignancy
  • Thrombophilia screening (coagulation studies)
    • Indication: young patients, unusual thrombus localization, positive family history
    • Tests should be performed at the earliest 2 weeks after discontinuing anticoagulation
  • General tumor screening

References:[9][10][11][12][13][14][15]

Differential diagnoses

References:[16][12][17]

The differential diagnoses listed here are not exhaustive.

Treatment

Anticoagulation

  • Acute therapy
  • Secondary prophylaxis
    • Warfarin with target therapeutic INR of 2.0–3.0
    • Duration of treatment
      • First thrombosis: usually 3–6 months
        • For life (or until cured) in malignant disease
        • For 6 months, possibly for life, for confirmed thrombophilia
        • For at least 3 months, possibly for life (if there is no increased risk of bleeding), in idiopathic distal thrombosis
        • For 3 months in case of temporary risk factor (e.g., surgery, immobility)
      • If confirmed thrombophilia and recurrent thrombosis: indefinite

Additional therapy

References:[9][18][19][1][3][20][21][22]

Complications

References:[1]

We list the most important complications. The selection is not exhaustive.

Prevention

  • Preventive measures
  • Indications (based on assessment of risk factors, see “Etiology” above)
    • Low thrombosis risk: exercise, compression stockings
    • Medium and high thrombosis risk: anticoagulation

References:[23][1]