Deep vein thrombosis (Phlebothrombosis)

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.

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]

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]

• 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]

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
  • Indication: idiopathic thrombosis (esp. patients > 50 years)
  • Tests: CBC, renal function tests, liver function tests, urinalysis; , and chest x-ray.
  • Ensure up-to-date on all age-appropriate cancer screening (e.g. colonoscopy, mammogram, digital rectal exam, etc.)

References:^{[9][10][11][12][13][14][15]}

• Thrombophlebitis
  • Definition: inflammation of a superficial vein
  • Risk factors: hypercoagulable states (e.g., Factor V Leiden), pregnancy, cancer (e.g., pancreatic cancer)
  • Symptoms: subcutaneous, cord-shaped palpable structure, with erythema and tenderness
  • Diagnostics: Duplex ultrasound shows vascular wall thickening and subcutaneous edema.
  • Treatment
    • If symptoms are recent: stab incision with thrombectomy
    • If symptoms are > 7 days: compression stockings, mobilization, NSAID
    • Anticoagulation (e.g., LMWH): consider if large veins (e.g., great saphenous vein) are affected, or if thrombus approaches the deep venous system
• Compartment syndrome
• Torn muscle fiber and posttraumatic swelling/hematoma
• Lymphedema
• Erysipelas
• Varicose veins

References:^[16][12][17]

The differential diagnoses listed here are not exhaustive.

Anticoagulation

• Acute therapy
  • Heparin bolus plus constant heparin infusion for 4–5 days
    • Unfractionated heparin or low molecular weight heparin (see also parenteral anticoagulation)
    • Alternatively fondaparinux (factor Xa inhibitor)
  • Target: achieve and maintain an aPTT of 1.5–2.5 times the mean of the control value or upper normal limit
  • Simultaneous initiation of warfarin once aPTT is therapeutic
• 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

• Thrombolysis
  • Goal: faster resolution of thrombi
  • Indications
    • Slow response to anticoagulation
    • Pulmonary embolism with hemodynamic instability
    • Possibly for acute proximal DVT of the leg
  • Agents: streptokinase, urokinase, tissue plasminogen activator
  • Catheter-directed thrombolysis: administration of the thrombolytic agent directly at the site of obstruction via venous catheter
• Thrombectomy
  • Intravenous thrombus removal via catheter
  • Indications
    • Insufficient response to anticoagulation and thrombolysis
    • Extensive thrombus
    • Phlegmasia cerulea dolens
  • Low-dose heparin required prior to the procedure
• Inferior vena cava filter (Greenfield filter)
  • Indicated for patients at high risk of developing pulmonary embolism who have contraindications to anticoagulation, thrombolysis, and thrombectomy
  • Can prevent pulmonary embolism, but not DVT
• Compression therapy with bandages or stockings
• Early mobilization as tolerated, as little bedrest as possible!

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

• Pulmonary embolism
• Postthrombotic syndrome (valvular incompetence, residual venous obstruction)

References:^[1]

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