Epidemiology and Risk Factors
- More common in Caucasians
- Incidence is slightly higher in males and increases with age.
- Proximal deep vein thrombosis (DVTs) are more likely to cause pulmonary embolism (PE).
- 10% of proximal leg vein DVTs will lead to PE.
- 50% of untreated proximal DVTs will lead to PE within 3 months.
- > 90% of PEs are due to lower leg DVTs.
Resulting in endothelial damage:
- Smoking: Oxidant gases and other chemicals in cigarette smoke produce free radicals that lead to platelet aggregation and an increase in the production of procoagulant molecules.
- Hypertension: Increased shear stress leads to damage of the endothelium.
- 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 an 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): 20 times increased risk of developing a DVT
- Age > 60
Resulting in hypercoagulability:
- Hereditary thrombophilia
- Factor V Leiden
- Protein C or S deficiency
- Elevated levels of homocysteine
- Pregnancy/oral contraceptive pill (OCP) use: Estrogen increases the production of clotting factors in the liver.
- 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:
- Prior DVT/pulmonary embolism: 30 times increased risk of recurrent DVT/PE
- Family history
To remember DVT risk factors, think THROMBOSIS.
- Hypercoagulable/Hormone replacement therapy (HRT)
- Recreational drugs
- Old (age > 60)
- Blood disorders
- Sickness (congestive heart failure [CHF]/myocardial infarction [MI], inflammatory bowel disease [IBD], nephrotic syndrome, vasculitis)
Site of origin
- Deep vein thrombosis commonly beings 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
- During pregnancy: pelvis veins
Composition of thrombus
- Red blood cells
Three pathophysiologic mechanisms (Virchow’s 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
Complications of DVT
- Pulmonary embolism:
- Potentially fatal
- Occurs as a result of mechanical obstruction of the pulmonary artery or its branches by a variety of materials (e.g., thrombus, air, or fat)
- Has both cardiovascular and respiratory effects (hypotension and hypoxia)
- 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 the long term on lower extremities.
- Mobility can be reduced.
- Some patients experience paresthesias.
- Occurs in 25%–50% of all patients with DVT
- Symptoms/manifestations are usually unilateral.
- Intact distal pulses
- Fever (due to cytokine release)
- Homan sign: calf pain on dorsiflexion of the foot (neither sensitive nor specific)
- The 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 1 extremity → limited arterial flow → manifestations:
- 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
First test, depending on degree of suspicion
- If the suspicion of DVT is high (Wells score > 2), the test of choice is ultrasonography with Doppler. Diagnostic imaging findings include:
- 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
|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|
|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., digital rectal exam [DRE], mammography, colonoscopy)
- Coagulation studies are indicated in patients with:
- Positive family history
- Young age
- Unusual localization of thrombus
- Hemodynamic stable with a DVT and signs of pulmonary embolism (e.g., chest pain, dyspnea): contrast-enhanced computed tomography (CT) scan of the chest
- Hemodynamically unstable with DVT and signs of pulmonary embolism: echocardiogram to visualize right ventricular dilation
- A 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 (limits the usefulness of ultrasound)
- 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 low-molecular-weight heparin (LMWH)
- Secondary prevention of DVT
- Initiate warfarin once activated partial thromboplastin time (aPTT) is 1.5–2.5x 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 international normalized ratio (INR), but is more expensive
- Other preventive measures
- Early mobilization after surgery
- Postoperative anticoagulation
- 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 (systolic blood pressure < 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 inferior vena cava (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
- Fasciotomy if compartment syndrome present
- Fibrinolysis if thrombectomy fails
- Amputation: if both thrombectomy and fibrinolysis fail, leading to critical limb ischemia and limb loss
- Treatment of upper extremity DVT
- Anticoagulation (LMWH/unfractionated heparin [UFH]/fondaparinux)
- Fibrinolysis if refractory/large thrombus
The following condtions are differential diagnoses of DVT:
- Peripheral vascular disease: a chronic disease involving arteries in the extremities, and the main cause of intermittent claudication. 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: localized fluid retention and tissue swelling caused by a compromised lymphatic system. Lymphedema can be caused by surgery, parasitic infections, or hereditary conditions. The condition is often bilateral, unlike a DVT, which is unilateral.
- Cellulitis: a condition that presents with localized swelling, warmth, redness, and pain in an area. Cellulitis is an infection of the dermis and subcutaneous fat and may form abscesses.