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 
- 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
- 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-Hypercoagulability, E-Endothelial damage, S-Stasis.
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
Subtypes and variants
Phlegmasia cerulea dolens
- 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)
Upper extremity deep vein thrombosis (UEDVT) 
- Proximal UEDVT: thrombosis of the axillary or subclavian vein
- Distal UEDVT: thrombosis of the brachial, radial, ulnar, or interosseus veins
- Primary UEDVT (Paget-Schroetter syndrome): UEDVT due to an underlying anatomical abnormality, repetitive injury to the vein, or an unknown cause
- Secondary UEDVT: UEDVT due to an indwelling device in the vein or a hypercoagulable state
- UEDVT is less common than lower extremity DVT.
- Primary UEDVT typically occurs in young individuals, while secondary UEDVT typically occurs in older adults.
- Secondary UEDVT is more common than primary UEDVT.
- Proximal UEDVT is more common than distal UEDVT with the subclavian vein being the most commonly affected.
- Multiple vein involvement occurs in approx. 60% of patients with UEDVT.
- Venous thoracic outlet syndrome due to increased muscle bulk, fibrotic connective tissue, abnormal ligamentous insertion, or osseous abnormalities (e.g., cervical rib)
- Effort-induced thrombosis: repetitive strenuous activity involving the upper extremities (e.g., weight-lifting, gymnastics, operation of a jackhammer)
- Secondary UEDVT
- Symptoms tend to be more severe with proximal UEDVT than with distal UEDVT.
- Acute thrombosis
- Often asymptomatic until complete occlusion occurs
- Even with complete occlusion, symptoms are often nonspecific or minimal as drainage through collateral veins can partially compensate for occlusion.
- Calculate the pretest probability of UEDVT using the dichotomized Constans score. 
- UEDVT likely (dichotomized Constans score ≥ 2): perform duplex ultrasonography or measure D-dimers
- UEDVT unlikely (dichotomized Constans score < 2): measure D-dimers
- If D-dimers are negative: UEDVT can be ruled out.
- If D-dimers are positive: perform duplex ultrasonography
- If initial duplex ultrasonography is negative but clinical suspicion remains high:
- If primary UEDVT is suspected: Consider a chest x-ray to screen for bone abnormalities (see “Diagnostics” in “ ”).
- If secondary UEDVT due to a hypercoagulable state is suspected: Consider screening for occult malignancy or inherited thrombophilia (see “Diagnostics” in “ ”).
- Proximal UEDVT
- Distal UEDVT
- Anticoagulation therapy in UEDVT
Further treatment based on the underlying cause
- Primary UEDVT: Consider thoracic outlet decompression surgery if symptoms persist despite anticoagulation and thrombolysis.
Secondary UEDVT due to a venous device
- Leave the device in situ if the patient has proximal UEDVT and does not have an indication for device removal.
- Indications for device removal
- Neurologic or arterial thoracic outlet syndrome
- Superior vena cava syndrome
- Complex regional pain syndrome
- Secondary lymphedema
- Brachial neuritis
- Quadrilateral pain syndrome
- Cervical nerve root compression
- Peripheral nerve compression
Pretest probability of DVT
- 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|
|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) 
Diagnostic approach for suspected lower-extremity DVT 
This approach is valid for evaluating a first-episode or recurrent lower extremity DVT. 
- Calculate the pretest probability ( ) using .
- Check D-dimer first for low PTP (initial D-dimer is not diagnostically helpful for intermediate and high PTP). ; 
- Negative (< 500 ng/mL): DVT ruled out
- Positive (≥ 500 ng/mL): Possible DVT; Proceed to venous US.
- Obtain venous ultrasound (US) for intermediate or high PTP, or low PTP with positive D-Dimer 
The positive yield of investigations for concomitant DVT (i.e., using the Wells score, D-Dimer, and/or venous ultrasound) is low for patients with a high likelihood of lower extremity cellulitis. A selective rather than routine approach to evaluating for DVT is preferred in these patients to avoid unnecessary testing. 
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 ultrasound findings of DVT 
- 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- and technique-dependent
- Whole leg study by radiology: high sensitivity and specificity (∼ 95%) for proximal DVT; lower sensitivity and specificity (∼ 65%) for distal DVT 
- Point of care ultrasound study (POCUS) by trained nonradiologists: equivalent accuracy for detection of proximal DVT, but distal DVT may be missed 
If appropriately trained, consider performing a POCUS study to quickly rule in a proximal DVT. If the study is negative, further investigations (e.g., a whole leg ultrasound study by radiology) may be necessary. 
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 
- Muscle or soft tissue injury (i.e., posttraumatic swelling or hematoma)
- Ruptured popliteal cyst
The differential diagnoses listed here are not exhaustive.
- 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
- 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 
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)
- Prophylactic regimen (for 45 days)
- Therapeutic regimen (for at least 3 months)
- Evaluate and treat concomitant pulmonary embolism and stabilize the patient as needed.
- 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.
Consider empiric in unstable or pulseless patients with obvious signs of DVT. 
|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 and involves an initial transient period of parenteral anticoagulation (bridging anticoagulation) followed by long-term (typically 3–6 months) oral 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
- Bridging anticoagulation required
- 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) 
- 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).
These interventions are not routinely indicated.
- Catheter-directed thrombolysis (CDT) 
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. 
- Educate the patient regarding prescribed anticoagulation and the recognition of warning signs.
- Ensure outpatient follow-up within 1–2 weeks.
- Hospital admission during the acute phase is recommended for patients with:
Prior to discharge, educate patients regarding prescribed anticoagulation and advise them to immediately seek medical attention if they develop worsening pain or swelling, shortness of breath, chest pain, or signs of bleeding.
Estimation of bleeding risk with anticoagulation
Risk factors for bleeding in patients with VTE 
- Age > 65 years
- Decreased functional capacity and comorbidity
- Frequent falls
- Past medical history
- Chronic conditions
- Medication history
- Laboratory abnormalities
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 device
- Preferred in seriously ill medical patients and in surgical patients
- Alternating inflation and deflation of the compression device improve venous return by simulating the calf pump mechanism.
- 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. 
- : Pulmonary emboli most commonly originate in the proximal deep veins of the lower extremities (e.g., iliac, femoral, or popliteal veins).
- Septic thrombophlebitis: may occur in patients with a history of IV drug use using nonsterile needles
Venous gangrene (rare complication) 
- The development of ischemic necrosis of a distal extremity despite palpable or doppler pulses, occurring as a complication of deep vein thrombosis
- Often associated with the use of warfarin in patients with acquired hypercoagulability (e.g., in malignancy, heparin-induced thrombocytopenia, antiphospholipid syndrome).
We list the most important complications. The selection is not exhaustive.
Acute management checklist for acute DVT
- 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.
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