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Deep vein thrombosis

Last updated: September 21, 2023

Summarytoggle arrow icon

Deep vein thrombosis (DVT) is the formation of a blood clot within the deep veins, 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.

Definitiontoggle arrow icon

Etiologytoggle arrow icon

Any factor that causes hypercoagulability, endothelial damage, and/or venous stasis can cause DVT (see “Virchow triad”).

Risk factors for venous thromboembolism [6][7]
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)!

References:[10][11]

Pathophysiologytoggle arrow icon

The Virchow triad

The Virchow triad refers to the three main pathophysiological components of thrombus formation.

  1. Hypercoagulability: increased platelet adhesion, thrombophilia (e.g., factor V Leiden mutation), use of oral contraceptives, pregnancy
  2. Endothelial damage: Inflammatory or traumatic vessel injuries can lead to activation of clotting factors through contact with exposed subendothelial collagen.
  3. 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.

References:[10][12][13]

Clinical featurestoggle arrow icon

Deep vein thrombosis may be asymptomatic.

References:[10][15]

Subtypes and variantstoggle arrow icon

Phlegmasia cerulea dolens

Upper extremity deep vein thrombosis (UEDVT) [16]

Definitions

Epidemiology

Etiology

Clinical features

  • Symptoms tend to be more severe with proximal UEDVT than with distal UEDVT.
  • Acute thrombosis
    • Discoloration, swelling, and/or pain in the affected arm
    • Superficial venous engorgement
  • Chronic 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.

Management [17][18][19]

Differential diagnosis

Complications

Pretest probability of DVTtoggle arrow icon

Modified Wells criteria for deep vein thrombosis [21][22][23]
Criteria Score
Medical history Active cancer + 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

+ 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

+ 1
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) [17]

  • 0: low
  • 1–2: intermediate
  • ≥ 3: high

The Wells score can overestimate the probability of DVT in patients with concomitant signs of lower extremity cellulitis due to overlap in the clinical manifestations. [24]

Diagnosticstoggle arrow icon

Diagnostic approach for suspected lower-extremity DVT [4][17][25]

This approach is valid for evaluating a first-episode or recurrent lower extremity DVT. [17]

  • Calculate the pretest probability (PTP) using Wells criteria for DVT.
  • Check D-dimer first for low PTP (initial D-dimer is not diagnostically helpful for intermediate and high PTP). ; [26]
    • 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 [25]
    • Negative US
      • Intermediate and low PTP: DVT ruled out
      • High PTP: Repeat venous US within a week if no alternate diagnosis. [4]
    • Positive US: DVT confirmed; Screen for an underlying cause if no risk factors for DVT are identified on initial evaluation.
    • Inconclusive US: Consider venography, CT venography, or MR venography.

A negative D-dimer can help rule out DVT without venous ultrasound in patients with low pretest probability. It is not helpful for patients with intermediate or high pretest probability.

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. [24]

Initial evaluation of DVT

Based on the patient's pretest probability, the initial test to evaluate for DVT may be either D-dimer or compression ultrasound.

Severe swelling and edema with concomitant coldness, cyanosis, and pulselessness should raise concern for phlegmasia cerulea dolens, which requires emergency surgery.

D-dimer [17][25]

  • Indication: preferred initial test for nonpregnant patients with a low PTP of DVT (Wells score = 0)
  • Interpretation
    • Cutoff for normal range is typically 500 ng/mL
    • Some centers use age-adjusted D-dimer cutoffs (See also “Diagnostics” in “Pulmonary embolism”) [27][28][29]
  • Accuracy
    • High sensitivity (∼ 96%)
    • Low specificity (∼ 36%) [4]
    • Not reliable for ruling out DVT in patients with intermediate or high PTP

In patients with a low pretest probability of DVT, a negative D-dimer (< 500 ng/mL) rules out DVT. [17]

A positive D-dimer alone does not confirm DVT. [17]

Lower extremity venous ultrasound [4][17][25][30]

Compression ultrasound of the whole leg with color Doppler (i.e., duplex scanning) is the most accurate test for diagnosing DVT. [25]

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. [32][33]

Additional evaluation

Routine laboratory studies

These are recommended to assess organ function and bleeding risk prior to anticoagulation.

Venography, CT venography, or MR venography [4][30]

Screening for an underlying cause

Patients with the following may require additional evaluation: unprovoked DVT, unexplained recurrent VTE, and/or a history suggestive of a hypercoagulable state or occult malignancy. [2]

Differential diagnosestoggle arrow icon

In patients with suspected cellulitis AND risk factors for DVT or no response to antibiotics, consider compression ultrasound to rule out DVT. [24]

The differential diagnoses listed here are not exhaustive.

Superficial thrombophlebitistoggle arrow icon

Definition

Risk factors

Risk factors for concomitant DVT [19][38]

Clinical features

Diagnostics

Superficial thrombophlebitis is typically a clinical diagnosis. The primary differential diagnoses are localized skin or soft tissue inflammation (e.g., cellulitis, vasculitis) [38][41]

Treatment [19][42]

All patients should be evaluated and treated for concomitant pulmonary embolism or DVT.

Complications

Treatmenttoggle arrow icon

Approach [7][26]

Consider empiric management of pulmonary embolism in unstable or pulseless patients with obvious signs of DVT. [19][45]

Therapeutic approach to DVT [7][25][26]
Options Indications
Expectant management
(i.e., serial venous ultrasound over 2 weeks)

Primary treatment only
(i.e., anticoagulation for 3–6 months)

Primary treatment PLUS secondary prevention
(i.e., anticoagulation for 3–6 months PLUS extended anticoagulation of indefinite duration)

Advanced therapy
(e.g., catheter-directed thrombolysis, thrombectomy, IVC filter)

Expectant management [7][25][26]

  • Indication: asymptomatic or only mildly symptomatic isolated distal DVT without risk factors for clot extension
  • Relative contraindications
  • Measures
    • Serial venous US for 2 weeks after symptom onset to identify clot extension
    • If evidence of clot extension is:
      • Absent: No further management is required.
      • Confined to distal veins: Consider anticoagulation.
      • Involves proximal veins: Initiate anticoagulation.

Primary treatment (anticoagulation) [7][26][46]

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)

Treatment with heparin (especially UFH) can cause heparin-induced thrombocytopenia. For early detection, perform regular CBCs.

Long-term anticoagulation (for 3–6 months)

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. [7][26]

Secondary prevention (extended anticoagulation of indefinite duration) [7][26][46]

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 bleeding risk on anticoagulation for VTE.

  • Indications: See “Therapeutic approach to DVT.”
  • Options [26]
    • 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). [26][46]

Advanced therapy

These interventions are not routinely indicated.

Supportive care [26]

Disposition [7][26][46]

  • Outpatient therapy is preferred for patients with uncomplicated DVT. [59]
    • 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 anticoagulationtoggle arrow icon

Risk factors for bleeding in patients with VTE [26]

Risk assessment

Risk of major bleeding on anticoagulant therapy in patients with VTE [26]
Risk category First 3 months of therapy After 3 months of therapy

Low

(No risk factors)

1.6% 0.8%/year

Moderate

(1 risk factor)

3.2% 1.6%/year

High

(≥ 2 risk factors)

12.8% ≥ 6.5%/year

Preventiontoggle arrow icon

VTE prophylaxis refers to the primary prevention 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 risk factors for VTE and estimated risk of bleeding on anticoagulation therapy. [60]

  • General preventive measures
    • Regular exercise
    • Early postoperative mobilization
    • Physiotherapy
    • Avoid certain medications (e.g., OCPs) in patients with thrombophilias (e.g., factor V Leiden).
  • Pharmacological VTE prophylaxis (antithrombotics): 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 [60]
Approach to VTE prophylaxis [60][61][62]
Indications Choice of prophylaxis [63][64]
Low-risk patients
At-risk outpatients
  • First-line: mechanical prophylaxis preferred; consider LMWH, e.g., enoxaparin as an alternative
  • Second-line: full-dose ASA [65]

Medical inpatients

  • Seriously ill or critically ill patients without high bleeding risk [66][67]
  • Seriously ill or critically ill medical patients with high bleeding risk

Surgical patients

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 risk factors for VTE.

In surgical patients, the first dose of the antithrombotic should be administered within 12 hours of completing the surgery. [61]

LMWH or low-dose UFH is recommended for postoperative anticoagulation in patients who have undergone major surgery.

Complicationstoggle arrow icon

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

Acute management checklist for acute DVTtoggle arrow icon

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Referencestoggle arrow icon

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