- Clinical science
Deep vein thrombosis (DVT) is the formation of a blood clot within the , most commonly those of the lower extremities. The main risk factors for DVT are vascular endothelial damage (e.g., surgery or trauma), venous stasis (e.g., immobility), and hypercoagulability (e.g., thrombophilia), collectively referred to as the Virchow triad. Symptoms include edema, warmth, and dull pain of the affected extremity. Patients may also present with features of pulmonary embolism (PE), a severe complication of DVT. The Wells criteria for DVT are used to determine the pretest probability (PTP) of DVT. The initial test of choice for DVT is D-dimer in patients with a low PTP and venous ultrasound (US) in patients with moderate or high PTP. A negative D-dimer assay (i.e., levels < 500 ng/mL) allows DVT to be ruled out, while a positive D-dimer (levels ≥ 500 ng/mL) is nonspecific and requires a venous ultrasound to confirm the diagnosis. Noncompressibility of the affected vein is the most important sonographic feature of DVT. Primary treatment with long-term anticoagulation for 3–6 months is recommended in all patients with DVT, with the exception of isolated asymptomatic distal DVT, for which expectant management with serial ultrasound may be considered, as the risk of postthrombotic sequelae is low. Secondary prevention (i.e., anticoagulation extended indefinitely after completion of primary treatment) is also recommended for select patients, depending on the extent and etiology of the DVT and on the patient's bleeding risk. Catheter-directed thrombolysis or thrombectomy may be considered for limb-threatening ischemia, acute iliofemoral DVT, and patients with contraindications to anticoagulation. Primary prevention of VTE is recommended in patients at risk of DVT or PE (e.g., seriously ill medical patients, most surgical patients, and long-distance travelers with additional risk factors for VTE) and includes mechanical and pharmacological measures.
Deep vein thrombosis (DVT): the formation of one or more blood clots in a deep vein, typically of the lower extremities 
- Proximal DVT: DVT of the lower extremity affecting the femoral vein, profunda femoris vein, and/or the popliteal vein (up to the calf vein trifurcation) 
- Distal DVT: DVT of the lower extremity that is confined to the veins beyond the calf vein trifurcation (i.e., below the knee joint)
- Provoked DVT: DVT in an individual with ≥ 1
- Unprovoked DVT (idiopathic DVT): DVT in an individual without
- Venous thromboembolism (VTE): an umbrella term that encompasses DVT and (PE)
|Risk factors for venous thromboembolism |
|Transient risk factors||Chronic risk factors|
Remember DVT risk factors using the mnemonic “THROMBOSIS”: Travel, Hypercoagulable/HRT, Recreational drugs, Old (> 60), Malignancy, Blood disorders, Obesity/Obstetrics, Surgery/Smoking, Immobilization, Sickness (CHF/MI, IBD, nephrotic syndrome, vasculitis)!
The Virchow triad
The Virchow triad refers to the three main pathophysiological components of thrombus formation.
- Hypercoagulability: increased platelet adhesion, (e.g., ), use of oral contraceptives, pregnancy
- Endothelial damage: Inflammatory or traumatic vessel injuries can lead to activation of clotting factors through contact with exposed subendothelial collagen.
- Venous stasis: varicosis, external pressure on the extremity, immobilization (e.g., hospitalization, bed rest, long flights or bus rides), local application of heat
To remember the three pathophysiological components of thrombus formation, think: “HE'S Virchow”: H-Hypercoaguability, E-Endothelial damage, S-Stasis.
- May be asymptomatic
Localized unilateral symptoms
- Typically affects deep veins of the legs, thighs, or pelvis
- Swelling, feeling of tightness or heaviness
- Warmth, erythema, and possibly livid discoloration
- Progressive tenderness, dull pain
- Distention of superficial veins
- Distal pulses are normal.
- General symptoms: fever 
- Possible signs of pulmonary embolism: dyspnea, chest pain, dizziness, weakness
- The Wells score for DVT, also known as the Wells criteria, is used to calculate the T of DVof the lower extremities. 
- A different version of the score is used to determine the probability of PE (see “ ”).
|Modified Wells criteria for deep vein thrombosis |
|Medical history||+ 1|
|Previously documented DVT||+ 1|
|Immobilization||Paralysis, paresis, or recent (cast) immobilization of lower extremity||+ 1|
Recently bedridden for ≥ 3 days OR underwent major surgery within the past 12 weeks under general/local anesthesia
|Clinical features||Tenderness localized along the deep venous system||+ 1|
|Swelling of the entire leg||+ 1|
Calf swelling ≥ 3 cm compared to the contralateral leg
|Pitting edema confined to the symptomatic leg||+ 1|
|Distended collateral superficial veins (nonvaricose)||+ 1|
|Differential diagnosis||Alternative diagnosis as likely as or more likely than DVT||- 2|
Interpretation (pretest probability for DVT) 
Approach to lower extremity DVT 
This approach is valid for evaluating a first-episode or recurrent lower extremity DVT, based on the pretest probability ( ): See “ .” 
|Diagnostic approach for suspected lower-extremity DVT |
|Test result||Pretest probability|
|Initial D-dimer||Negative (< 500 ng/mL)||DVT ruled out||Initial D-dimer is not diagnostically helpful in this risk group. |
|Positive (≥ 500 ng/mL)||Possible DVT; proceed to venous US|
|Venous ultrasound (US) ||Negative||DVT ruled out||Repeat venous US within a week if no alternate diagnosis |
|Positive||DVT confirmed; screen for an underlying cause if noare identified on initial evaluation.|
|Inconclusive||Consider venography, CT venography, or MR venography.|
Initial evaluation of DVT
- Indication: preferred initial test for nonpregnant patients with a low PTP of DVT (Wells score = 0)
A positive D-dimer alone does not confirm DVT. 
Lower extremity venous ultrasound 
- Compression ultrasound: The vein is identified and external pressure is directly applied over it with the probe.
- Venous compression ultrasound
: can be added to
- Involves the addition of color Doppler
- Allows for better evaluation of noncompressible deep veins 
Supportive findings 
- Noncompressibility of the obstructed vein
- Intraluminal hyperechoic mass
- Distention of the affected vein
- On Doppler imaging
- Of recurrent DVT: thrombosis in a new venous segment or a > 4 mm increase in noncompressibility of the obstructed vein
- Accuracy: : operator-dependent; high sensitivity and specificity (∼ 95%) for proximal DVT; lower sensitivity and specificity (∼ 65%) for distal DVT 
Routine laboratory studies
These are recommended to assess organ function and bleeding risk prior to anticoagulation.
- Liver chemistries
- Coagulation studies
Venography, CT venography, or MR venography 
- Finding: intraluminal filling defect
Screening for an underlying cause
- Thrombophilia screening 
Screening for occult malignancy 
- Indications: unprovoked VTE (esp. patients > 50 years), recurrent VTE, unusual thrombus location
- Investigations: routine age-appropriate cancer screening recommended 
- Inflammation and thrombosis of a superficial vein
- Varicose veins 
- Venous cannulation, IV drug administration
Risk factors for concomitant DVT 
- Age ≥ 75 years
- Past history of VTE
- Superficial thrombophlebitis affecting nonvaricose veins or veins above the knee 
- Recent immobilization, surgery, or trauma
- Pregnancy, recent childbirth, use of estrogen therapy
- Obesity, autoimmune disease, thrombophilia, CHF, or active cancer
- Pain, tenderness, induration, and erythema overlying a superficial vein, often with a palpable cord (the thrombosed vein)
- Most commonly affects the superficial veins of the leg
- Concomitant DVT and/or PE present in ∼ 25% of patients (see “” and “”) 
Compression ultrasound with/without Doppler
- Indication: presence of any risk factor for concomitant DVT or if the clinical diagnosis is unclear
- Findings: thickened, edematous, noncompressible superficial vein with/without an intraluminal thrombus, with/without extension into a deep vein
- Evaluation for the underlying cause: same as that for DVT (see “Diagnostics" above)
All patients should be evaluated and treated for concomitant pulmonary embolism or DVT.
Symptomatic care: indicated for all patients 
- Oral and/or topical analgesics: See “ .”
- Compression therapy with graduated compression stockings
Anticoagulation: to consider based on thrombus length (e.g., ≥ 5 cm), location (i.e., proximity to the deep venous system), and risk factors for DVT
- Not required in the following circumstances: (i.e., provide symptomatic care only)
- Superficial thrombophlebitis caused by venous cannulation
- Thrombus length < 5 cm without risk factors for concomitant DVT
- Prophylactic regimen (for 45 days)
- Therapeutic regimen (for at least 3 months)
- Indication: any length thrombus located < 3 cm from the SFJ
- Options: See “Long-term anticoagulation” in “Treatment.”
- Not required in the following circumstances: (i.e., provide symptomatic care only)
- Evaluate and treat concomitant pulmonary embolism.
- Assess .
- Initiate anticoagulation therapy based on the extent and etiology of DVT: See “.”
- Expectant management: serial venous ultrasound without anticoagulation
- Primary treatment: anticoagulation for 3–6 months in patients not being managed expectantly
- Secondary prevention; (of recurrent DVT): extended anticoagulation ; after completion of primary treatment; should be individualized (e.g., patients with chronic risk factors)
- Treat the underlying cause, if feasible.
|Therapeutic approach to DVT |
Expectant management |
(i.e., serial venous ultrasound over 2 weeks)
Primary treatment only
Primary treatment PLUS secondary prevention
Advanced therapy |
(e.g., catheter-directed thrombolysis, thrombectomy, IVC filter)
Expectant management 
- Indication: asymptomatic or only mildly symptomatic isolated distal DVT without risk factors for clot extension
- Relative contraindications
Primary treatment (anticoagulation) 
Primary treatment is the duration of anticoagulation required to treat an acute DVT (typically 3–6 months). Most patients receive long-term treatment with oral anticoagulants, which often require bridging therapy with initial parenteral anticoagulation.
Initial parenteral anticoagulation (for the first 5–10 days)
- Low molecular weight heparin (LMWH); (e.g., enoxaparin; ) : preferred in pregnant women and patients with normal renal function, liver disease, or active cancer 
- Fondaparinux (factor Xa inhibitor) : preferred in patients with a history of
- Unfractionated heparin (UFH) bolus plus infusion; : preferred in patients with renal failure, inadequate subcutaneous absorption (i.e., morbid obesity), and those at a high risk of bleeding 
Long-term anticoagulation (for 3–6 months)
- Indication: all patients with DVT who cannot be managed expectantly and have no contraindications to anticoagulation. (See “”)
Direct oral anticoagulants (DOACs): first-line therapy in nonpregnant patients (preferred over VKAs) 
- Regular monitoring of coagulation parameters is not required.
- Associated with a lower risk of major bleeding
- Options (any of the following)
- Dabigatran and edoxaban require parenteral lead-in therapy while rivaroxaban and apixaban can be started immediately 
Vitamin K antagonists (VKAs): warfarin
- Requires bridging therapy
- Second-line therapy in nonpregnant patients
- Requires dose adjustment to maintain a target INR of 2–3
- LMWH: preferred in pregnant women; and in patients with active cancer; , e.g., enoxaparin 
Initial parenteral anticoagulation (with LMWH, fondaparinux, or UFH) should be initiated at the same time as warfarin and before dabigatran and edoxaban. Initial parenteral anticoagulation is not required for patients receiving rivaroxaban or apixaban. 
Secondary prevention (extended anticoagulation of indefinite duration) 
The decision to extend anticoagulation indefinitely after primary treatment is typically made after balancing the risk of recurrent DVT (e.g., for patients with chronic risk factors) with the .
- Indications: See “ .”
- First episode of DVT: Continue the same anticoagulant used for long-term anticoagulation (e.g., warfarin, or DOACs).
- Recurrent DVT while appropriately anticoagulated
- Patients wishing to discontinue anticoagulation : Consider aspirin (unless there are contraindications)
- Monitoring: Reassess bleeding risk periodically (e.g., annually).
Extended anticoagulation is usually not required in patients with a provoked DVT due to a transient or reversible risk factor (e.g., surgery, intravascular catheter). 
These are not routinely indicated.
- Catheter-directed thrombolysis (CDT) 
- Indications: same as for CDT; consider as an alternative to CDT in patients with 
Inferior vena cava filter (Greenfield filter)
- Indications 
Supportive care 
- Encourage early ambulation; minimize bedrest. 
- Graduated compression stockings
- Analgesics for pain relief: See “ ”; avoid NSAIDs if the patient is receiving anticoagulation or thrombolytics. 
- Delay any elective surgery for at least 3 months after initiation of anticoagulation therapy. 
- Outpatient therapy is preferred for patients with uncomplicated DVT.
- Hospital admission during the acute phase is recommended for patients with:
- Age > 65 years
- Decreased functional capacity and comorbidity
- Frequent falls
Past medical history
- Prior history of bleeding
- Prior history of stroke
- Recent surgery
- Chronic conditions
- Medication history
- Laboratory abnormalities
|Risk of major bleeding on anticoagulant therapy in patients with VTE |
|Risk category||First 3 months of therapy||After 3 months of therapy|
(No risk factors)
(1 risk factor)
(≥ 2 risk factors)
VTE prophylaxis refers to the of DVT or PE in at-risk individuals and includes general preventive measures, mechanical VTE prophylaxis, and pharmacological VTE prophylaxis. VTE prophylaxis should be chosen based on the presence of and . 
- General preventive measures
- Pharmacological VTE prophylaxis ( ): LMWH, low-dose UFH, and DOACs are recommended.
Mechanical VTE prophylaxis
- Graduated compression stockings: preferred in long-distance travelers
- Intermittent pneumatic compression stockings: preferred in seriously ill medical patients and in surgical patients
- Duration of prophylaxis in hospitalized patients 
|Approach to VTE prophylaxis |
|Indications||Choice of prophylaxis |
|Low-risk patients|| |
|At-risk outpatients|| |
| || |
| || |
Prophylaxis is usually indicated in seriously ill patients who are hospitalized, patients undergoing major surgery, patients with major trauma, and long-distance travelers with additional .
In surgical patients, the first dose of the antithrombotic should be administered within 12 hours of completing the surgery. 
- Definition: : a severe form of phlebothrombosis characterized by obstruction of all veins of one extremity, with subsequent restriction of arterial flow; ; associated with high mortality
- Complications: shock, gangrene, acute renal failure (due to rhabdomyolysis)
Paget-Schroetter disease (upper extremity DVT)
- Definition: acute thrombosis of a brachial, axial, or subclavian vein
- Treatment: anticoagulation, fibrinolysis, surgery (e.g., first rib resection) for thoracic outlet syndrome 
- Determine the pretest probability (PTP) of DVT (see “Wells score”).
- Choose diagnostic algorithm according to PTP:
- Obtain baseline laboratory studies: e.g., CBC, BMP, liver chemistries, coagulation studies
- If no obvious trigger: Screen for underlying cause (e.g., thrombophilia, malignancy).
- Assess for features of pulmonary embolism and initiate treatment for PE if needed: See “Acute management checklist for PE.”
- Assess bleeding risk: See "Estimated risk of major bleeding on anticoagulation therapy in patients with VTE."
- Initiate anticoagulation therapy based on extent of DVT (see “Therapeutic approach to DVT”).
- Treat the underlying cause, if feasible.