Deep vein thrombosis

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.

• Deep vein thrombosis (DVT): the formation of one or more blood clots in a deep vein, typically of the lower extremities ^[1][2][3]
  • 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) ^[4]
  • 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 risk factor for VTE
  • Unprovoked DVT (idiopathic DVT): DVT in an individual without risk factors for VTE
• Venous thromboembolism (VTE): an umbrella term that encompasses DVT and pulmonary embolism (PE)
  • Recurrent VTE: DVT and/or PE that recurs in a patient after the completion of the first 2 weeks of antithrombotic therapy. ^[5]

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

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]

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]

• May be asymptomatic
• Localized unilateral symptoms
  • Typically affects deep veins of the legs, thighs, or pelvis
    • More common in the left lower extremity
    • May-Thurner syndrome: compression of the left iliac vein between the right iliac artery and a lumbar vertebral spur (occurs in > 20% of adults) ^[14][15]
  • Swelling, feeling of tightness or heaviness
  • Warmth, erythema, and possibly livid discoloration
  • Progressive tenderness, dull pain
    • Homans sign: calf pain on dorsal flexion of the foot
    • Meyer sign: Compression of the calf causes pain.
    • Payr sign: pain when pressure is applied over the medial part of the sole of the foot
  • Distention of superficial veins
  • Distal pulses are normal.
• General symptoms: fever ^[16]
• Possible signs of pulmonary embolism: dyspnea, chest pain, dizziness, weakness

References:^[10][17]

• The Wells score for DVT, also known as the Wells criteria, is used to calculate the pretest probability of DVT of the lower extremities. ^[18][19]
• A different version of the score is used to determine the probability of PE (see “Wells criteria for PE”).

Approach to lower extremity DVT ^[4][21][22]

This approach is valid for evaluating a first-episode or recurrent lower extremity DVT, based on the pretest probability (PTP): See “Wells criteria for DVT.” ^[21]

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.

D-dimer ^[21][22]

• 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”) ^[24][25][26]
• 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. ^[21]

A positive D-dimer alone does not confirm DVT. ^[21]

Lower extremity venous ultrasound ^{[4][21][22][27]}

• Indications
  • Preferred initial test for patients with moderate or high PTP of lower extremity DVT (Wells score ≥ 1)
  • Preferred initial test for pregnant or postsurgical patients even if the PTP of DVT is low
  • Next diagnostic step in patients with a low PTP of lower extremity DVT but a positive D-dimer
• Procedures ^[22]
  • Compression ultrasound: The vein is identified and external pressure is directly applied over it with the probe.
    • Proximal leg: allows for evaluation of the femoral and popliteal veins up to the trifurcation
    • Whole leg: allows for evaluation of the proximal leg PLUS distal calf veins (beyond the trifurcation)
  • Venous duplex ultrasound: can be added to compression ultrasound
    • Involves the addition of color Doppler
    • Allows for better evaluation of noncompressible deep veins ^[28]
• Supportive findings ^[28]
  • Noncompressibility of the obstructed vein
  • Intraluminal hyperechoic mass
  • Distention of the affected vein
  • On Doppler imaging
    • Absent venous flow (complete obstruction) or abnormal venous flow (partial obstruction)
    • Inadequate augmentation of venous flow on distal calf compression or Valsalva maneuver
  • 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 ^[27]

Compression ultrasound of the whole leg with color Doppler (i.e., duplex scanning) is the most accurate test for diagnosing DVT. ^[22]

Additional evaluation

Routine laboratory studies

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

• CBC
• BMP
• Liver chemistries
• Coagulation studies
  • Assess the patient's baseline coagulation status
  • Screen for subtherapeutic INR in patients on VKA therapy with suspected recurrent DVT

Venography, CT venography, or MR venography ^[4][27]

• Indications
  • Inconclusive findings on compression US
  • Inability to perform compression US due to, e.g., obesity, significant lower limb edema, immobilization cast
• Finding: intraluminal filling defect

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]

• Thrombophilia screening ^[2]
  • Thrombosis in patients < 45 years
  • Unusual thrombus localization
  • Positive family history
  • Recurrent or multiple thromboses
  • Recurrent pregnancy loss
  • See “Diagnostics” in “Hypercoagulable states.”
• Screening for occult malignancy ^[2][29][30]
  • Indications: unprovoked VTE (esp. patients > 50 years), recurrent VTE, unusual thrombus location
  • Investigations: routine age-appropriate cancer screening recommended ^[29][30]
    • In addition to routine laboratory studies: consider e.g., urinalysis, FOBT, serum calcium levels
    • Consider CXR, colonoscopy, mammogram, digital rectal exam, Pap smear

• Superficial thrombophlebitis
• Muscle or soft tissue injury (i.e., posttraumatic swelling or hematoma)
• Lymphedema
• Venous insufficiency
• Ruptured popliteal cyst
• Cellulitis
• Compartment syndrome

The differential diagnoses listed here are not exhaustive.

Definition

• Inflammation and thrombosis of a superficial vein
• Variants
  • Thrombophlebitis migrans (Trousseau syndrome)
  • Superficial thrombophlebitis of the breast (Mondor disease)

Risk factors

• Risk factors for VTE
• Varicose veins ^[31]
• Venous cannulation, IV drug administration
• Behçet disease
• Thromboangiitis obliterans ^[32]

Risk factors for concomitant DVT ^[33][34]

• Age ≥ 75 years
• Past history of VTE
• Superficial thrombophlebitis affecting nonvaricose veins or veins above the knee ^[34][35]
• Recent immobilization, surgery, or trauma
• Pregnancy, recent childbirth, use of estrogen therapy
• Obesity, autoimmune disease, thrombophilia, CHF, or active cancer

Clinical features

• 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 “Clinical features of DVT” and “Clinical features of PE”) ^[33][35][36]

Diagnostics

Superficial thrombophlebitis is typically a clinical diagnosis. The primary differential diagnoses are localized skin or soft tissue inflammation (e.g., cellulitis, vasculitis) ^[33][37]

• 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)

Treatment ^[34][38]

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

• Symptomatic care: indicated for all patients ^[34]
  • Oral and/or topical analgesics: See “Pain management.”
  • 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)
    • Indications
      • Thrombus length ≥ 5 cm located > 3 cm away from the SFJ
      • Thrombus length < 5 cm with any risk factors for concomitant DVT
    • Options
      • Rivaroxaban ^[39]
      • Fondaparinux ^[40]
      • LMWH, such as enoxaparin : preferred in pregnant patients
  • Therapeutic regimen (for at least 3 months)
    • Indication: any length thrombus located < 3 cm from the SFJ
    • Options: See “Long-term anticoagulation” in “Treatment.”

Complications

• DVT
• Pulmonary embolism
• Infection (septic thrombophlebitis)

Approach ^[7][23]

• Evaluate and treat concomitant pulmonary embolism.
• Assess bleeding risk on anticoagulation for VTE.
• Initiate anticoagulation therapy based on the extent and etiology of DVT: See “Therapeutic approach to DVT.”
  • 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.

Primary treatment (anticoagulation) ^[7][23][41]

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)

• Indications
  • Bridging therapy for VKAs: parenteral anticoagulation overlaps with oral anticoagulation until therapeutic INR is maintained.
  • Parenteral lead-in therapy for dabigatran and edoxaban: These DOACs are started after completion of lead-in parenteral therapy without overlapping.
• Options:
  • Low molecular weight heparin (LMWH); (e.g., enoxaparin; ) : preferred in pregnant women and patients with normal renal function, liver disease, or active cancer ^[34][42]
  • Fondaparinux (factor Xa inhibitor) : preferred in patients with a history of heparin-induced thrombocytopenia
  • 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 ^[41][43]

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

Long-term anticoagulation (for 3–6 months)

• Indication: all patients with DVT who cannot be managed expectantly and have no contraindications to anticoagulation. (See “Therapeutic approach to DVT”)
• Direct oral anticoagulants (DOACs): first-line therapy in nonpregnant patients (preferred over VKAs) ^[44][45]
  • Regular monitoring of coagulation parameters is not required.
  • Associated with a lower risk of major bleeding
  • Options (any of the following)
    • Direct factor Xa inhibitors: rivaroxaban , apixaban , or edoxaban
    • Direct thrombin inhibitors: dabigatran
  • Dabigatran and edoxaban require parenteral lead-in therapy while rivaroxaban and apixaban can be started immediately ^[44]
• Vitamin K antagonists (VKAs): warfarin
  • Requires bridging therapy
    • Initiate simultaneously with initial parenteral anticoagulation
    • Continue parenteral anticoagulation with warfarin for at least 5 days and until therapeutic INR has been maintained for 48 hours ^[45][46]
  • 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 ^[44]

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][23]

Secondary prevention (extended anticoagulation of indefinite duration) ^[7][23][41]

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 ^[23]
  • First episode of DVT: Continue the same anticoagulant used for long-term anticoagulation (e.g., warfarin, or DOACs).
  • Recurrent DVT while appropriately anticoagulated
    • On an oral anticoagulant: Switch to LMWH; either temporarily or for the remaining duration of therapy (e.g., enoxaparin ).
    • On LMWH: Increase LMWH dose by 25–33%
  • 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). ^[23][41]

Advanced therapy

These are not routinely indicated.

• Catheter-directed thrombolysis (CDT) ^[7][23]
  • Indications
    • Limb-threatening ischemia (phlegmasia cerulea dolens)
    • Consider in acute (< 14 days) iliofemoral DVT in patients with low risk of bleeding and life expectancy ≥ 1 year ^[23][47]
  • Agents: streptokinase, urokinase, rtPA ^[47]
• Thrombectomy
  • Indications: same as for CDT; consider as an alternative to CDT in patients with absolute contraindications to thrombolysis ^[47]
• Inferior vena cava filter (Greenfield filter)
  • Indications ^[23][48]
    • DVT with a high risk of PE (e.g., proximal DVT) in patients with contraindications for anticoagulation, absolute contraindications to thrombolysis, and contraindications to thrombectomy (e.g., patients with active bleeding, recent major surgery, recent intracranial hemorrhage) ^[49]
    • Consider in anticoagulated patients with severe PE to prevent subsequent PE. ^[23][48]

Supportive care ^[23]

• Encourage early ambulation; minimize bedrest. ^[50][51][52]
• Graduated compression stockings
  • Consider only for symptomatic relief (i.e., reduction of edema and pain)
  • No longer routinely recommended to prevent postthrombotic syndrome. ^[23][41]
• Analgesics for pain relief: See “Pain management”; avoid NSAIDs if the patient is receiving anticoagulation or thrombolytics. ^[53]
• Delay any elective surgery for at least 3 months after initiation of anticoagulation therapy. ^[41]

Risk factors for bleeding in patients with VTE ^[23]

• Patient characteristics
  • 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
  • Cancer
  • Renal failure
  • Liver failure
  • Diabetes
  • Alcohol use disorder
• Medication history
  • Poor anticoagulant control
  • Antiplatelet therapy
  • NSAID use
• Laboratory abnormalities
  • Low platelets
  • Anemia

Risk assessment

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. ^[54]

• 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 stockings: preferred in seriously ill medical patients and in surgical patients
• Duration of prophylaxis in hospitalized patients ^[54]
  • Mechanical VTE prophylaxis: until the patient is mobile
  • Pharmacological VTE prophylaxis
    • Seriously ill medical patients: at least 7 days; extend to span the duration of hospitalization
    • Surgical patients: consider extended therapy for > 3 weeks ^[55]

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. ^[55]

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

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
• Symptoms
  • Severe swelling, edema, and pain
  • Coldness, cyanosis, and pulselessness
• Treatment
  • Emergency surgery: venous thrombectomy, fasciotomy
  • Fibrinolysis if surgery fails
  • Amputation as last resort
• 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
• Etiology
  • Effort-induced thrombosis: triggered by repetitive strenuous activity of the upper extremities (e.g., weight-lifting, operation of a jackhammer)
  • Thoracic outlet syndrome
  • Presence of a foreign object in veins (e.g., central venous catheter, pacemaker lead)
• Treatment: anticoagulation, fibrinolysis, surgery (e.g., first rib resection) for thoracic outlet syndrome ^[62]

References:^[62][63]

• Pulmonary embolism: Pulmonary emboli most commonly originate in the proximal deep veins of the lower extremities.
• Postthrombotic syndrome (chronic venous insufficiency)

References:^[10]

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

• Determine the pretest probability (PTP) of DVT (see “Wells score”).
• Choose diagnostic algorithm according to PTP:
  • Low PTP: D-dimer followed by lower extremity venous ultrasound.
  • Intermediate/high PTP: Start with lower extremity venous ultrasound.
  • Consider CT/MR venography if inconclusive.
• 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.

1. Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis.. Lancet (London, England). 1995; 345 (8961): p.1326-30. doi: 10.1016/s0140-6736(95)92535-x . | Open in Read by QxMD
2. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003; 349 (13): p.1227-1235. doi: 10.1056/nejmoa023153 . | Open in Read by QxMD
3. Engelberger RP et al.. Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis. Thromb Res. 2011; 127 (6): p.535-539. doi: 10.1016/j.thromres.2011.02.008 . | Open in Read by QxMD
4. Lim W et al.. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv. 2018; 2 (22): p.3226-3256. doi: 10.1182/bloodadvances.2018024828 . | Open in Read by QxMD
5. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease. Chest. 2016; 149 (2): p.315-352. doi: 10.1016/j.chest.2015.11.026 . | Open in Read by QxMD
6. Di Nisio et al.. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev. 2004 . doi: 10.1002/14651858.cd004982 . | Open in Read by QxMD
7. Perttu ET Arkkila. Thromboangiitis obliterans (Buerger's disease). Orphanet J Rare Dis. 2006; 1 (1). doi: 10.1186/1750-1172-1-14 . | Open in Read by QxMD
8. Quéré I et al.. Superficial venous thrombosis and compression ultrasound imaging. J Vasc Surg. 2012; 56 (4): p.1032-1038.e1. doi: 10.1016/j.jvs.2012.03.014 . | Open in Read by QxMD
9. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.. Chest. 2012; 141 (2 Suppl): p.e419S-e496S. doi: 10.1378/chest.11-2301 . | Open in Read by QxMD
10. Konkle BA. Superficial venous thrombosis: cause for concern. Blood. 2013; 122 (10): p.1691-1692. doi: 10.1182/blood-2013-07-514067 . | Open in Read by QxMD
11. Sobreira ML, Maffei FH, Yoshida WB, et al. Prevalence of deep vein thrombosis and pulmonary embolism in superficial thrombophlebitis of the lower limbs: prospective study of 60 cases.. Int Angiol. 2009; 28 (5): p.400-8.
12. Ellis MH, Fajer S. A current approach to superficial vein thrombosis.. Eur J Haematol. 2013; 90 (2): p.85-8. doi: 10.1111/ejh.12044 . | Open in Read by QxMD
13. Scott G, Mahdi AJ, Alikhan R. Superficial vein thrombosis: a current approach to management. Br J Haematol. 2014; 168 (5): p.639-645. doi: 10.1111/bjh.13255 . | Open in Read by QxMD
14. Beyer-Westendorf J, Schellong SM, Gerlach H, et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. The Lancet Haematology. 2017; 4 (3): p.e105-e113. doi: 10.1016/s2352-3026(17)30014-5 . | Open in Read by QxMD
15. Decousus H et al.. Fondaparinux for the Treatment of Superficial-Vein Thrombosis in the Legs. N Engl J Med. 2010; 363 (13): p.1222-1232. doi: 10.1056/nejmoa0912072 . | Open in Read by QxMD
16. Piazza G, Goldhaber SZ. Acute pulmonary embolism: part I: epidemiology and diagnosis.. Circulation. 2006; 114 (2): p.e28-32. doi: 10.1161/CIRCULATIONAHA.106.620872 . | Open in Read by QxMD
17. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Advances. 2020; 4 (19): p.4693-4738. doi: 10.1182/bloodadvances.2020001830 . | Open in Read by QxMD
18. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis.. Ann Intern Med. 1996; 125 (1): p.1-7. doi: 10.7326/0003-4819-125-1-199607010-00001 . | Open in Read by QxMD
19. Al-Azzawi HF, Obi OC, Safi J, Song M. Nephrotic syndrome-induced thromboembolism in adults.. International journal of critical illness and injury science. undefined; 6 (2): p.85-8. doi: 10.4103/2229-5151.183019 . | Open in Read by QxMD
20. Patel K. Deep Venous Thrombosis. Deep Venous Thrombosis. New York, NY: WebMD. http://emedicine.medscape.com/article/1911303. Updated: March 30, 2016. Accessed: February 13, 2017.
21. ENGBERS MJ, VAN HYLCKAMA VLIEG A, ROSENDAAL FR. Venous thrombosis in the elderly: incidence, risk factors and risk groups. J Thromb Haemost. 2010; 8 (10): p.2105-2112. doi: 10.1111/j.1538-7836.2010.03986.x . | Open in Read by QxMD
22. Lip GYH, Hull RD. Overview of the treatment of lower extremity deep vein thrombosis (DVT). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-the-treatment-of-lower-extremity-deep-vein-thrombosis-dvt?source=see_link§ionName=SUMMARY%20AND%20RECOMMENDATIONS&anchor=H42#H42.Last updated: February 6, 2017. Accessed: February 13, 2017.
23. Iliofemoral Deep Vein Thrombosis. http://www.acc.org/latest-in-cardiology/articles/2015/11/23/13/39/iliofemoral-deep-vein-thrombosis. Updated: October 24, 2015. Accessed: February 27, 2017.
24. Birn J, Vedantham S. May–Thurner syndrome and other obstructive iliac vein lesions: Meaning, myth, and mystery. Vascular Medicine. 2014; 20 (1): p.74-83. doi: 10.1177/1358863x14560429 . | Open in Read by QxMD
25. Peters M, Syed RK, Katz M, et al. May-Thurner syndrome: a not so uncommon cause of a common condition. Proc (Bayl Univ Med Cent). 2012; 25 (3): p.231-233.
26. Branchford BR, Carpenter SL. The Role of Inflammation in Venous Thromboembolism. Frontiers in Pediatrics. 2018; 6 . doi: 10.3389/fped.2018.00142 . | Open in Read by QxMD
27. Thompson BT. Clinical presentation, evaluation, and diagnosis of the adult with suspected acute pulmonary embolism. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-presentation-evaluation-and-diagnosis-of-the-adult-with-suspected-acute-pulmonary-embolism.Last updated: December 9, 2016. Accessed: February 14, 2017.
28. Mall NA, Van Thiel GS, Heard WM, Paletta GA, Bush-Joseph C, Bach BR. Paget-Schroetter Syndrome. Sports Health. 2013; 5 (4): p.353-356. doi: 10.1177/1941738112470911 . | Open in Read by QxMD
29. Mumoli N, Invernizzi C, Luschi R, Carmignani G, Camaiti A, Cei M. Phlegmasia cerulea dolens. Circulation. 2012; 125 (8): p.1056-1057. doi: 10.1161/circulationaha.111.051912 . | Open in Read by QxMD
30. Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT. Chest. 2012; 141 (2): p.e351S-e418S. doi: 10.1378/chest.11-2299 . | Open in Read by QxMD
31. Needleman L, Cronan JJ, Lilly MP, et al. Ultrasound for Lower Extremity Deep Venous Thrombosis. Circulation. 2018; 137 (14): p.1505-1515. doi: 10.1161/circulationaha.117.030687 . | Open in Read by QxMD
32. Patel H, Sun H, Hussain AN, Vakde T. Advances in the Diagnosis of Venous Thromboembolism: A Literature Review. Diagnostics. 2020; 10 (6): p.365. doi: 10.3390/diagnostics10060365 . | Open in Read by QxMD
33. Schouten HJ, Koek HL, Oudega R, et al. Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis. BMJ. 2012; 344 (jun06 1): p.e2985-e2985. doi: 10.1136/bmj.e2985 . | Open in Read by QxMD
34. Schouten HJ, Geersing GJ, Koek HL, et al. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ. 2013; 346 : p.f2492-f2492. doi: 10.1136/bmj.f2492 . | Open in Read by QxMD
35. Ho VB et al.. ACR Appropriateness Criteria® on Suspected Lower Extremity Deep Vein Thrombosis. J Am Coll Radiol. 2011; 8 (6): p.383-387. doi: 10.1016/j.jacr.2011.02.016 . | Open in Read by QxMD
36. Desjardins B, Hanley M, Steigner ML, et al. ACR Appropriateness Criteria® Suspected Upper Extremity Deep Vein Thrombosis. Journal of the American College of Radiology. 2020; 17 (5): p.S315-S322. doi: 10.1016/j.jacr.2020.01.020 . | Open in Read by QxMD
37. Parakh RS, Sabath DE. Venous Thromboembolism: Role of the Clinical Laboratory in Diagnosis and Management.. The journal of applied laboratory medicine. 2019; 3 (5): p.870-882. doi: 10.1373/jalm.2017.025734 . | Open in Read by QxMD
38. Van Es N, Le Gal G, Otten H-M, et al. Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism. Ann Intern Med. 2017; 167 (6): p.410. doi: 10.7326/m17-0868 . | Open in Read by QxMD
39. Carrier M, Lazo-Langner A, Shivakumar S, et al. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. 2015; 373 (8): p.697-704. doi: 10.1056/nejmoa1506623 . | Open in Read by QxMD
40. Wilbur J, Shian B. Deep Venous Thrombosis and Pulmonary Embolism: Current Therapy.. Am Fam Physician. 2017; 95 (5): p.295-302.
41. Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of Pulmonary Embolism. J Am Coll Cardiol. 2016; 67 (8): p.976-990. doi: 10.1016/j.jacc.2015.11.061 . | Open in Read by QxMD
42. Smythe MA, Priziola J, Dobesh PP, Wirth D, Cuker A, Wittkowsky AK. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.. J Thromb Thrombolysis. 2016; 41 (1): p.165-86. doi: 10.1007/s11239-015-1315-2 . | Open in Read by QxMD
43. van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials.. Blood. 2014; 124 (12): p.1968-75. doi: 10.1182/blood-2014-04-571232 . | Open in Read by QxMD
44. Gómez-Outes A, Terleira-Fernández AI, Lecumberri R, Suárez-Gea ML, Vargas-Castrillón E. Direct oral anticoagulants in the treatment of acute venous thromboembolism: A systematic review and meta-analysis. Thromb Res. 2014; 134 (4): p.774-782. doi: 10.1016/j.thromres.2014.06.020 . | Open in Read by QxMD
45. Wigle P, Hein B, Bloomfield HE, Tubb M, Doherty M. Updated guidelines on outpatient anticoagulation.. Am Fam Physician. 2013; 87 (8): p.556-66.
46. Casey ET et al.. Treatment of acute iliofemoral deep vein thrombosis. J Vasc Surg. 2012; 55 (5): p.1463-1473. doi: 10.1016/j.jvs.2011.12.082 . | Open in Read by QxMD
47. Bikdeli B et al.. Inferior Vena Cava Filters to Prevent Pulmonary Embolism. J Am Coll Cardiol. 2017; 70 (13): p.1587-1597. doi: 10.1016/j.jacc.2017.07.775 . | Open in Read by QxMD
48. White RH, Brunson A, Romano PS, Li Z, Wun T. Outcomes After Vena Cava Filter Use in Noncancer Patients With Acute Venous Thromboembolism: A Population-Based Study.. Circulation. 2016; 133 (21): p.2018-29. doi: 10.1161/CIRCULATIONAHA.115.020338 . | Open in Read by QxMD
49. Liu Z et al.. Bed Rest versus Early Ambulation with Standard Anticoagulation in The Management of Deep Vein Thrombosis: A Meta-Analysis. PLoS ONE. 2015; 10 (4): p.e0121388. doi: 10.1371/journal.pone.0121388 . | Open in Read by QxMD
50. Meune C, Aissaoui N, et al. Is bed rest recommendation in the management of patients with pulmonary embolism and/or deep vein thrombosis evidence-based medicine: A meta-analysis. Circulation. 2018 .
51. Aissaoui N, Martins E, Mouly S, Weber S, Meune C. A meta-analysis of bed rest versus early ambulation in the management of pulmonary embolism, deep vein thrombosis, or both.. Int J Cardiol. 2009; 137 (1): p.37-41. doi: 10.1016/j.ijcard.2008.06.020 . | Open in Read by QxMD
52. Risser A, Donovan D, Heintzman J, Page T. NSAID prescribing precautions.. Am Fam Physician. 2009; 80 (12): p.1371-8.
53. Schünemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Advances. 2018; 2 (22): p.3198-3225. doi: 10.1182/bloodadvances.2018022954 . | Open in Read by QxMD
54. Anderson DR et al.. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019; 3 (23): p.3898-3944. doi: 10.1182/bloodadvances.2019000975 . | Open in Read by QxMD
55. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in Nonsurgical Patients. Chest. 2012; 141 (2): p.e195S-e226S. doi: 10.1378/chest.11-2296 . | Open in Read by QxMD
56. Laryea J, Champagne B. Venous thromboembolism prophylaxis.. Clinics in colon and rectal surgery. 2013; 26 (3): p.153-9. doi: 10.1055/s-0033-1351130 . | Open in Read by QxMD
57. Chen A, Stecker E, A. Warden B. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. Journal of the American Heart Association. 2020; 9 (13). doi: 10.1161/jaha.120.017559 . | Open in Read by QxMD
58. Cesarone MR, Belcaro G, Nicolaides AN, et al. Venous thrombosis from air travel: the LONFLIT3 study--prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial.. Angiology. undefined; 53 (1): p.1-6. doi: 10.1177/000331970205300101 . | Open in Read by QxMD
59. William H. Geerts, Graham F. Pineo, John A. Heit, David Bergqvist, Michael R. Lassen, Clifford W. Colwell, Joel G. Ray. Prevention of Venous Thromboembolism. Chest. 2004; 126 (3): p.338S-400S. doi: 10.1378/chest.126.3_suppl.338s . | Open in Read by QxMD
60. Mandernach MW, Beyth RJ, Rajasekhar A. Apixaban for the prophylaxis and treatment of deep vein thrombosis and pulmonary embolism: an evidence-based review.. Therapeutics and clinical risk management. 2015; 11 : p.1273-82. doi: 10.2147/TCRM.S68010 . | Open in Read by QxMD
61. Kirkilesis G, Kakkos SK, Bicknell C, Salim S, Kakavia K. Treatment of distal deep vein thrombosis. Cochrane Database of Systematic Reviews. 2020 . doi: 10.1002/14651858.cd013422.pub2 . | Open in Read by QxMD
62. Galioto NJ, Danley DL, Van Maanen RJ. Recurrent venous thromboembolism.. Am Fam Physician. 2011; 83 (3): p.293-300.
63. Ageno W, Squizzato A, Wells PS, Büller HR, Johnson G. The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: guidance from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2013; 11 (8): p.1597-1602. doi: 10.1111/jth.12301 . | Open in Read by QxMD
64. Agabegi SS, Agabegi ED. Step-Up To Medicine. Lippincott Williams & Wilkins ; 2013
65. Kearon C, Bauer KA, Leung LLK, Mandel J, Finlay G. Clinical Presentation and Diagnosis of the Nonpregnant Adult With Suspected Deep Vein Thrombosis of the Lower Extremity. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-the-nonpregnant-adult-with-suspected-deep-vein-thrombosis-of-the-lower-extremity.Last updated: March 24, 2017. Accessed: October 6, 2017.
66. Deep Vein Thrombosis. https://radiopaedia.org/articles/deep-vein-thrombosis. . Accessed: October 6, 2017.
67. Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997; 350 (9094): p.1795-1798. doi: 10.1016/s0140-6736(97)08140-3 . | Open in Read by QxMD
68. Liepman CI, Koerber JM, Mattson JC, Westley SJ, Smythe MA. Comparing methods of establishing the aPTT therapeutic range of heparin. Ann Pharmacother. 2003; 37 (6): p.794-798. doi: 10.1345/aph.1c162 . | Open in Read by QxMD
69. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ. Antithrombotic therapy and prevention of thrombosis - 9th. Chest. 2012; 141 (2): p.7S-47S. doi: 10.1378/chest.1412s3 . | Open in Read by QxMD
70. Superficial Vein Thrombosis (SVT). http://www.dynamed.com/topics/dmp~AN~T116756/Superficial-vein-thrombosis-SVT#Management-1. Updated: August 10, 2018. Accessed: May 14, 2019.
71. Parry BA et al.. International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs. Thromb Res. 2018; 166 : p.63-70. doi: 10.1016/j.thromres.2018.04.003 . | Open in Read by QxMD
72. Matharu GS et al.. Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement. JAMA. 2020; 180 (3): p.376. doi: 10.1001/jamainternmed.2019.6108 . | Open in Read by QxMD