Deep vein thrombosis (DVT) is the most common form in the deep veins of the calf. The affected veins include the femoral, popliteal, and iliofemoral veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Ultrasound can visualize the thrombus and anticoagulation is the primary mode of treatment, the main objective is the prevention of development of a PE.

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Deep vein thrombosis of the right leg

Image: “A deep vein thrombosis of the right leg. Note the swelling and redness.” by James Heilman, MD. License: CC BY-SA 3.0


Epidemiology and Risk Factors

Epidemiology

  • More common in Caucasians
  • Proximal DVT is more likely to cause a pulmonary embolism
  • Incidence is slightly higher in males and increases with age
Epidemiology DVT

Image: “Epidemiology DVT” by Lecturio

Risk Factors

  • Resulting in endothelial damage
    • Smoking: Oxidant gases and other chemicals in the smoke produce free radicals which lead to platelet aggregation and increase in the production of procoagulant molecules.
    • Hypertension: increased shear stress leads to damage of the endothelium
    • Surgery
    • Vascular catheter placement (hemodialysis catheters, peripherally inserted central catheters (PICC) lines): most common cause of upper extremity DVT
    • Trauma, especially involving the vasculature
    • Nephrotic syndrome
      • Leads to loss of anticoagulant proteins (antithrombin III, protein C and S) via the urine due to damaged glomerular membranes
      • Leads to increase in the production of fibrinogen and other procoagulant proteins in the liver due to protein loss and hypoalbuminemia
    • Antiphospholipid syndrome
  • Resulting in venous stasis
    • Immobilization (long air travel, after orthopedic surgery: 20x increased risk of developing a DVT
    • Age > 60
    • Polycythemia
  • Resulting in hypercoagulability
    • Hereditary thrombophilia
      • Factor V Leiden
      • Protein C or S deficiency
      • Elevated levels of homocysteine
    • Pregnancy/OCP: estrogen increases the production of clotting factors in the liver
    • Obesity
    • Cancer: gastric, pancreatic, pulmonary, gynecologic, and urologic tumors particularly associated with increased risk of DVT → produce proteins and cytokines with thrombophilic effect
    • Chemotherapy: affects vascular endothelium, coagulation cascades, and tumor cell lysis
    • Heparin-induced thrombocytopenia
  • Other risk factors

Mnemonic

To remember DVT risk factors, think THROMBOSIS

  • Travel
  • Hypercoagulable/HRT
  • Recreational drugs
  • Old (age > 60)
  • Malignancy
  • Blood disorders
  • Obesity/Obstetrics
  • Surgery/Smoking
  • Immobilization
  • Sickness (CHF/MI, IBD, nephrotic syndrome, vasculitis)

Video Gallery

Deep Vein Thrombosis: Etiology by Joseph Alpert, MD
Deep Vein Thrombosis: Epidemiology by Joseph Alpert, MD
Deep Vein Thrombosis: Risk Factors by Joseph Alpert, MD

Pathophysiology

  • Site of origin
    • DVT commonly starts to form in the venous valves; the nature of the blood flow causes this area to be hypoxic.
    • Veins affected the most: femoral, popliteal, and iliofemoral veins
  • Composition of thrombus 
    • Red blood cells
    • Platelets
    • Fibrin
  • 3 pathophysiologic mechanisms (Virchow triad) 
    • Blood hypercoagulability: increased clotting factor synthesis (e.g., hypoxia-inducible factor-1) and increased platelet adhesion
    • Endothelial damage: Inflammation/trauma → exposure of tissue factor → conversion of prothrombin to thrombin → conversion of fibrinogen into fibrin and clot formation
    • Abnormal flow/stasis: Immobilization, venous valve incompetence → stasis of blood → clot formation
  • In contrast to DVT of lower extremity which is related to immobility, deep vein thrombosis of the upper extremity is usually triggered by repetitive/vigorous upper extremity engagement (e.g., weight lifting) and the presence of vascular catheters.
  • Complications of DVT
    • Pulmonary embolism
      • Potentially fatal condition that occurs as a result of mechanical obstruction of the pulmonary artery or its branches by a variety of materials (such as thrombus, air, or fat).
  • Chronic venous insufficiency
    • Due to wear and tear, congenital causes, or presence of thrombus 
    • Most superficial venous insufficiency is attributed to valvular conditions of the greater saphenous vein.
  • Post-thrombotic syndrome (most common complication of proximal DVT)
    • Symptoms include pain and swelling.
    • Ulcers develop in long-term on lower extremities.
    • Mobility can be reduced.
    • Some patients complain of paresthesias.
    • Occurs in 25–50% of all patients with DVT

Image: “DVT” Image shows main pathophysiologic mechanisms leading to deep vein thrombosis, namely: endothelial damage, blood hypercoagulability, and blood stasis. By Lecturio.

Video Gallery

Deep Vein Thrombosis: Pathogenesis by Joseph Alpert, MD

Clinical manifestations

  • Symptoms/manifestations are usually unilateral.
    • Pain
    • Warmth
    • Edema
    • Intact distal pulses
    • Fever (due to cytokine release)
    • Homan sign: calf pain on dorsiflexion of the foot (neither sensitive nor specific)
    • First manifestation can be pulmonary embolism (e.g., chest pain, dyspnea)
    • Chronic DVT can be asymptomatic and cause chronic venous insufficiency.
  • Phlegmasia cerulea dolens: obstruction of all veins of one extremity → limited arterial flow → manifestations:
    • Edema
    • Pulselessness
    • Pain
    • Cyanosis
  • Phlegmasia alba dolens: total occlusion of deep iliofemoral venous system → significant fluid sequestration, edema, and white coloring
    • Presents with edema, pain, and blanching without cyanosis
    • Edema precipitates phlegmasia cerulea dolens and compartment syndrome → arterial occlusion and impending limb ischemia
    • First described in pregnant and postpartum women

Image: “Successful treatment of posttraumatic phlegmasia cerulea dolens by reconstructing the external iliac vein” The image shows erythema, swelling, and cyanosis in a patient with phlegmasia cerulea dolens.
a. Initial appearance of the left leg, showing significant swelling and cyanosis. b. Appearance of the left leg 35 days after the operation, at the time of the patient’s discharge. By Hu H, Cai Y, Wang C, Yang C, Duan Z, Zhang J, Xin S. License: CC BY 2.0

Video Gallery

Deep Vein Thrombosis: Symptoms by Joseph Alpert, MD

Diagnostics

  • If the suspicion of DVT is high (Wells score > 2), the test of choice is ultrasonography with doppler.
    • Diagnostic imaging findings:
      • Lumen is noncompressible.
      • Hyperechoic mass
      • Decreased/absent flow
  • If the suspicion of DVT is low (Wells score < 2), the first test should be D-dimer:
    • Highly sensitive test
    • Negative test rules out DVT
    • Positive test warrants ultrasonography for confirmation
Wells criteria for DVT (identifies the probability of DVT)

Wells score > 2: DVT is likely (first test: US)

Wells score < 2: DVT is unlikely (first test: D-dimer)

Tenderness along with deep venous system +1
Unilateral pitting edema +1
Swelling of the entire leg +1
Calf swelling ≥ 3 cm (compared to asymptomatic calf) +1
Collateral superficial non-varicose veins +1
Active cancer +1
Previous DVT +1
Paralysis or cast immobilization +1
Bedridden ≥ 3 days or major surgery within past 12 weeks +1
Alternative diagnosis as likely/more likely than DVT -2
  • Age-appropriate screening (e.g., DRE, mammography, colonoscopy)
  • Coagulation studies are indicated in:
    • Positive family history
    • Young age
    • Unusual localization of thrombus
    • Recurrence 
  • Hemodynamic stable with a DVT and signs of pulmonary embolism (e.g., chest pain, dyspnea): Contrast-enhanced CT scan of the chest 
  • Hemodynamically unstable with DVT and signs of pulmonary embolism: Echocardiogram to visualize right ventricular dilation
  • Venography
    • Most accurate test for DVT 
    • Invasive and only done in patients with equivocal findings on non-invasive tests, or in those with severe obesity/edema(limit the usefulness of ultrasound).

Image: “Swedish algorithm of deep vein thrombosis” Diagnostic algorithm for DVT, If Wells score <2: the first test is D-dimer if Wells score >2: the first test is ultrasound. By Lecturio.

Treatment

  • Initial treatment
    • Heparin bolus (80 units/kg) + heparin infusion (18 units/kg/hr) for 4–5 days
    • Alternative to heparin: fondaparinux (indirect factor Xa inhibitor)
    • In patients with renal failure, unfractionated heparin is preferred over fondaparinux and LMWH
  • Secondary prevention of DVT
    • Initiate warfarin once aPTT is 1.5–2.5 x normal (continue only heparin if the patient has increased risk of bleeding/peptic ulcer disease)
    • Alternative to warfarin for secondary prophylaxis
      • Direct oral factor Xa inhibitor (e.g., rivaroxaban, apixaban)
      • Does not require regular monitoring of INR, but is more expensive
  • Other preventive measures
    • Early mobilization after surgery 
    • Postoperative anticoagulation
    • Exercise
    • Weight loss
    • Stopping smoking
    • Control of hypertension
    • Avoidance of OCPs
    • Compression stockings
  • Indications for thrombolysis (tPA, urokinase, streptokinase)
    • Large proximal DVT
    • Pulmonary embolism with hemodynamic instability (SBP < 90)
    • Refractory to anticoagulation
  • Indications for thrombectomy (removal of thrombus by a catheter)
    • Phlegmasia cerulea dolens
    • Large thrombus refractory to fibrinolysis
    • Large thrombus + contraindications to anticoagulation/thrombolytics
  • Indications for an IVC filter
    • Contraindications to anticoagulation/thrombolytics/thrombectomy (e.g, major bleeding)
    • Patients who have DVT or PE while on appropriate anticoagulation.
  • Treatment of phlegmasia alba dolens
    • Initiation of adequate anticoagulation
    • IV fluid resuscitation
  • Treatment of phlegmasia cerulea dolens
    • Initiation of adequate anticoagulation
    • Thrombectomy
    • Fasciotomy if compartment syndrome present
    • Fibrinolysis if thrombectomy fails
    • Amputation: if both thrombectomy and fibrinolysis fail to lead to critical limb ischemia and limb loss
  • Treatment of upper extremity DVT
    • Anticoagulation (LMWH/UFH/Fondaparinux)
    • Fibrinolysis if refractory/large thrombus

Video Gallery

Deep Vein Thrombosis: Therapy by Joseph Alpert, MD

Differential Diagnoses

  • Peripheral vascular disease: Peripheral vascular disease (the main cause of intermittent claudication) is a chronic disease involving arteries in the extremities. The chronic atherosclerotic process leads to arterial stenosis and, at a later stage, to the complete occlusion of the arteries (either from embolism or thrombosis).
  • Baker cyst: Baker cyst is a swelling in the popliteal space (space behind the knee).The pain worsens if the patient fully flexes or extends the knee. Baker cysts are commonly associated with rheumatoid arthritis. A ruptured Baker cyst can mimic an acute DVT.
  • Lymphedema: Refers to localized fluid retention and tissue swelling caused by a compromised lymphatic system, it can be caused by surgery, parasitic infections, or hereditary conditions. This is often bilateral unlike a DVT which is unilateral
  • Cellulitis: Presents with localized swelling, warmth, redness, and pain in an area. It is an infection of the dermis and subcutaneous fat and may form abscesses.
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