• Clinical science
  • Clinician

Deep vein thrombosis (Phlebothrombosis)

Summary

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.

Definition

Etiology

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
  • Surgical factors
  • Immobilization
    • Acute illness requiring complete bed rest
    • Lower extremity injury with restricted mobility for ≥ 3 days
    • Long-distance travel
  • Estrogen-related factors
  • Intravascular devices, such as:
  • Patient 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]

Pathophysiology

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-Hypercoaguability, E-Endothelial damage, S-Stasis.

References:[10][12][13]

Clinical features

References:[10][17]

Pretest probability of DVT

Modified Wells criteria for deep vein thrombosis [18][19][20]
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) [21]

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

Diagnostics

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

Diagnostic approach for suspected lower-extremity DVT [21][4][22]
Test result Pretest probability
Low Intermediate High
Initial D-dimer Negative (< 500 ng/mL) DVT ruled out Initial D-dimer is not diagnostically helpful in this risk group. [23]
Positive (≥ 500 ng/mL) Possible DVT; proceed to venous US
Venous ultrasound (US) [22] Negative DVT ruled out Repeat venous US within a week if no alternate diagnosis [4]
Positive DVT confirmed; screen for an underlying cause if no risk factors for DVT are identified on initial evaluation.
Inconclusive Consider venography, CT venography, or MR venography.

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 [21][27][4][22]

  • 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]
  • 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.

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

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 diagnoses

The differential diagnoses listed here are not exhaustive.

Superficial thrombophlebitis

Definition

Risk factors

Risk factors for concomitant DVT [33][34]

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) [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]
  • 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)
      • Indications
        • Thrombus length ≥ 5 cm located > 3 cm away from the SFJ
        • Thrombus length < 5 cm with any risk factors for concomitant DVT
      • Options
    • 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

Treatment

Approach [23][7]

Therapeutic approach to DVT [23][22][7]
Options Indications
Expectant management
(i.e., serial venous ultrasound over 2 weeks)
  • Isolated distal DVT without severe symptoms or risk factors for clot extension (see “Expectant management” for details) [23]

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

  • Isolated distal DVT with severe symptoms and/or risk factors for clot extension
  • Any of the following in a patient with high bleeding risk:
  • DVT provoked by a transient risk factor

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

  • Any of the following in a patient with low or moderate bleeding risk:
  • DVT provoked by chronic risk factors (e.g., active cancer, thrombophilia)
Advanced therapy
(e.g., catheter-directed thrombolysis, thrombectomy, IVC filter)
  • Consider in the following situations:
    • Acute iliofemoral DVT
    • Limb-threatening ischemia
    • DVT in a patient with contraindications to anticoagulation

Expectant management [23][22][7]

  • Indication: asymptomatic or only mildly symptomatic isolated distal DVT without risk factors for clot extension
  • Relative contraindications
    • Severe symptoms
    • Risk factors for clot extension
      • Markedly elevated D-dimer levels
      • Thrombosis > 5 cm in length and/or > 0.7 cm in diameter
      • Thrombosis of multiple distal veins
      • Thrombosis in close proximity to the proximal leg veins
      • Past history of VTE
  • 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) [23][41][7]

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)

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][23]

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

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
    • 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.

Supportive care [23]

  • Encourage early ambulation; minimize bedrest. [50][51][52]
  • Graduated compression stockings
  • 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]

Disposition [23][41][7]

  • Outpatient therapy is preferred for patients with uncomplicated DVT.
  • Hospital admission during the acute phase is recommended for patients with:

Estimation of bleeding risk with anticoagulation

Risk factors for bleeding in patients with VTE [23]

Risk assessment

Risk of major bleeding on anticoagulant therapy in patients with VTE [23]
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

Prevention

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]
Approach to VTE prophylaxis [54][55][56]
Indications Choice of prophylaxis [57][58]
Low-risk patients
At-risk outpatients
  • First-line: mechanical prophylaxis preferred; consider LMWH, e.g., enoxaparin as an alternative
  • Second-line: full-dose ASA [59]
  • Patients with active cancer PLUS additional VTE risk factors without high bleeding risk

Medical inpatients

  • Seriously ill or critically ill patients without high bleeding risk [60]
  • Seriously ill or critically ill medical patients with high bleeding risk

Surgical patients

  • Major surgeries (non-neurosurgical)
  • The following procedures in patients with risk factors for DVT:
    • Laparoscopic cholecystectomy
    • Urological surgery
  • Major trauma in a patient with low to moderate bleeding risk
  • The following procedures in patients without risk factors for DVT:
    • Major neurosurgical procedure
    • Laparoscopic cholecystectomy
    • Urological surgery
  • Major trauma in patients with high bleeding risk

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.

Subtypes and variants

Phlegmasia cerulea dolens

Paget-Schroetter disease (upper extremity DVT)

References:[63][62]

Complications

References:[10]

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

Acute management checklist for acute DVT

  • 1. 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.
  • 2. Parakh RS, Sabath DE. Venous Thromboembolism: Role of the Clinical Laboratory in Diagnosis and Management. The journal of applied laboratory medicine. 2019; 3(5): pp. 870–882. doi: 10.1373/jalm.2017.025734.
  • 3. Galioto NJ, Danley DL, Van Maanen RJ. Recurrent venous thromboembolism. Am Fam Physician. 2011; 83(3): pp. 293–300. pmid: 21302870.
  • 4. Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT. Chest. 2012; 141(2): pp. e351S–e418S. doi: 10.1378/chest.11-2299.
  • 5. 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): pp. 1597–1602. doi: 10.1111/jth.12301.
  • 6. Piazza G, Goldhaber SZ. Acute pulmonary embolism: part I: epidemiology and diagnosis. Circulation. 2006; 114(2): pp. e28–32. doi: 10.1161/CIRCULATIONAHA.106.620872.
  • 7. 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): pp. 4693–4738. doi: 10.1182/bloodadvances.2020001830.
  • 8. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996; 125(1): pp. 1–7. doi: 10.7326/0003-4819-125-1-199607010-00001.
  • 9. Al-Azzawi HF, Obi OC, Safi J, Song M. Nephrotic syndrome-induced thromboembolism in adults. International journal of critical illness and injury science. ; 6(2): pp. 85–8. doi: 10.4103/2229-5151.183019.
  • 10. Patel K. Deep Venous Thrombosis. In: Deep Venous Thrombosis. New York, NY: WebMD. http://emedicine.medscape.com/article/1911303. Updated March 30, 2016. Accessed February 13, 2017.
  • 11. 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): pp. 2105–2112. doi: 10.1111/j.1538-7836.2010.03986.x.
  • 12. 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.
  • 13. Foley TR, Waldo SW, Armstrong EJ. 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.
  • 14. Birn J, Vedantham S. May–Thurner syndrome and other obstructive iliac vein lesions: Meaning, myth, and mystery. Vascular Medicine. 2014; 20(1): pp. 74–83. doi: 10.1177/1358863x14560429.
  • 15. 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): pp. 231–233. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377287/.
  • 16. Branchford BR, Carpenter SL. The Role of Inflammation in Venous Thromboembolism. Frontiers in Pediatrics. 2018; 6. doi: 10.3389/fped.2018.00142.
  • 17. 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.
  • 18. Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet (London, England). 1995; 345(8961): pp. 1326–30. doi: 10.1016/s0140-6736(95)92535-x.
  • 19. 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): pp. 1227–1235. doi: 10.1056/nejmoa023153.
  • 20. 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): pp. 535–539. doi: 10.1016/j.thromres.2011.02.008.
  • 21. Lim W et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv. 2018; 2(22): pp. 3226–3256. doi: 10.1182/bloodadvances.2018024828.
  • 22. Needleman L, Cronan JJ, Lilly MP, et al. Ultrasound for Lower Extremity Deep Venous Thrombosis. Circulation. 2018; 137(14): pp. 1505–1515. doi: 10.1161/circulationaha.117.030687.
  • 23. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease. Chest. 2016; 149(2): pp. 315–352. doi: 10.1016/j.chest.2015.11.026.
  • 24. 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.
  • 25. 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): pp. e2985–e2985. doi: 10.1136/bmj.e2985.
  • 26. 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: pp. f2492–f2492. doi: 10.1136/bmj.f2492.
  • 27. Ho VB et al. ACR Appropriateness Criteria® on Suspected Lower Extremity Deep Vein Thrombosis. J Am Coll Radiol. 2011; 8(6): pp. 383–387. doi: 10.1016/j.jacr.2011.02.016.
  • 28. 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): pp. S315–S322. doi: 10.1016/j.jacr.2020.01.020.
  • 29. 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.
  • 30. Carrier M, Lazo-Langner A, Shivakumar S, et al. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. 2015; 373(8): pp. 697–704. doi: 10.1056/nejmoa1506623.
  • 31. Di Nisio et al. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev. 2004. doi: 10.1002/14651858.cd004982.
  • 32. Perttu ET Arkkila. Thromboangiitis obliterans (Buerger's disease). Orphanet J Rare Dis. 2006; 1(1). doi: 10.1186/1750-1172-1-14.
  • 33. Quéré I et al. Superficial venous thrombosis and compression ultrasound imaging. J Vasc Surg. 2012; 56(4): pp. 1032–1038.e1. doi: 10.1016/j.jvs.2012.03.014.
  • 34. 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): pp. e419S–e496S. doi: 10.1378/chest.11-2301.
  • 35. Konkle BA. Superficial venous thrombosis: cause for concern. Blood. 2013; 122(10): pp. 1691–1692. doi: 10.1182/blood-2013-07-514067.
  • 36. 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): pp. 400–8. pmid: 19935595.
  • 37. Ellis MH, Fajer S. A current approach to superficial vein thrombosis. Eur J Haematol. 2013; 90(2): pp. 85–8. doi: 10.1111/ejh.12044.
  • 38. Scott G, Mahdi AJ, Alikhan R. Superficial vein thrombosis: a current approach to management. Br J Haematol. 2014; 168(5): pp. 639–645. doi: 10.1111/bjh.13255.
  • 39. 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): pp. e105–e113. doi: 10.1016/s2352-3026(17)30014-5.
  • 40. Decousus H et al. Fondaparinux for the Treatment of Superficial-Vein Thrombosis in the Legs. N Engl J Med. 2010; 363(13): pp. 1222–1232. doi: 10.1056/nejmoa0912072.
  • 41. Wilbur J, Shian B. Deep Venous Thrombosis and Pulmonary Embolism: Current Therapy. Am Fam Physician. 2017; 95(5): pp. 295–302. pmid: 28290648.
  • 42. Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of Pulmonary Embolism. J Am Coll Cardiol. 2016; 67(8): pp. 976–990. doi: 10.1016/j.jacc.2015.11.061.
  • 43. 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): pp. 165–86. doi: 10.1007/s11239-015-1315-2.
  • 44. 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): pp. 1968–75. doi: 10.1182/blood-2014-04-571232.
  • 45. 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): pp. 774–782. doi: 10.1016/j.thromres.2014.06.020.
  • 46. Wigle P, Hein B, Bloomfield HE, Tubb M, Doherty M. Updated guidelines on outpatient anticoagulation. Am Fam Physician. 2013; 87(8): pp. 556–66. pmid: 23668445.
  • 47. Casey ET et al. Treatment of acute iliofemoral deep vein thrombosis. J Vasc Surg. 2012; 55(5): pp. 1463–1473. doi: 10.1016/j.jvs.2011.12.082.
  • 48. Bikdeli B et al. Inferior Vena Cava Filters to Prevent Pulmonary Embolism. J Am Coll Cardiol. 2017; 70(13): pp. 1587–1597. doi: 10.1016/j.jacc.2017.07.775.
  • 49. 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): pp. 2018–29. doi: 10.1161/CIRCULATIONAHA.115.020338.
  • 50. 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.
  • 51. 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. url: https://www.ahajournals.org/doi/10.1161/circ.116.suppl_16.II_698-d.
  • 52. 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): pp. 37–41. doi: 10.1016/j.ijcard.2008.06.020.
  • 53. Risser A, Donovan D, Heintzman J, Page T. NSAID prescribing precautions. Am Fam Physician. 2009; 80(12): pp. 1371–8. pmid: 20000300.
  • 54. 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): pp. 3198–3225. doi: 10.1182/bloodadvances.2018022954.
  • 55. 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): pp. 3898–3944. doi: 10.1182/bloodadvances.2019000975.
  • 56. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in Nonsurgical Patients. Chest. 2012; 141(2): pp. e195S–e226S. doi: 10.1378/chest.11-2296.
  • 57. Laryea J, Champagne B. Venous thromboembolism prophylaxis. Clinics in colon and rectal surgery. 2013; 26(3): pp. 153–9. doi: 10.1055/s-0033-1351130.
  • 58. 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.
  • 59. 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. ; 53(1): pp. 1–6. doi: 10.1177/000331970205300101.
  • 60. 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): pp. 338S–400S. doi: 10.1378/chest.126.3_suppl.338s.
  • 61. 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: pp. 1273–82. doi: 10.2147/TCRM.S68010.
  • 62. Mall NA, Van Thiel GS, Heard WM, Paletta GA, Bush-Joseph C, Bach BR. Paget-Schroetter Syndrome. Sports Health. 2013; 5(4): pp. 353–356. doi: 10.1177/1941738112470911.
  • 63. Mumoli N, Invernizzi C, Luschi R, Carmignani G, Camaiti A, Cei M. Phlegmasia cerulea dolens. Circulation. 2012; 125(8): pp. 1056–1057. doi: 10.1161/circulationaha.111.051912.
  • Weerakkody Y, Gaillard F et al. Deep Vein Thrombosis. https://radiopaedia.org/articles/deep-vein-thrombosis. Accessed October 6, 2017.
  • 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: pp. 63–70. doi: 10.1016/j.thromres.2018.04.003.
  • Gross P.L. 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.
  • Scovell C. Phlebitis and Thrombosis of the Superficial Lower Extremity Veins. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/phlebitis-and-thrombosis-of-the-superficial-lower-extremity-veins. Last updated September 18, 2018. Accessed October 26, 2018.
  • Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ. Antithrombotic therapy and prevention of thrombosis - 9th. Chest. 2012; 141(2): pp. 7S–47S. doi: 10.1378/chest.1412s3.
  • 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): pp. 794–798. doi: 10.1345/aph.1c162.
  • 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): pp. 1795–1798. doi: 10.1016/s0140-6736(97)08140-3.
  • Bauer KA. Approach to the diagnosis and therapy of lower extremity deep vein thrombosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/approach-to-the-diagnosis-and-therapy-of-lower-extremity-deep-vein-thrombosis?source=search_result&search=dvt&selectedTitle=1~150#H19. Last updated July 15, 2014. Accessed February 13, 2017.
  • 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.
  • Rosh AJ. Superficial Thrombophlebitis. In: Superficial Thrombophlebitis. New York, NY: WebMD. http://emedicine.medscape.com/article/463256-overview. Updated July 12, 2016. Accessed March 8, 2017.
  • Hull RD, Garcia DA. Heparin and LMW heparin: Dosing and adverse effects. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/heparin-and-lmw-heparin-dosing-and-adverse-effects. Last updated January 4, 2017. Accessed February 21, 2017.
  • Tapson VF. Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/fibrinolytic-thrombolytic-therapy-in-acute-pulmonary-embolism-and-lower-extremity-deep-vein-thrombosis?source=related_link. Last updated December 9, 2016. Accessed March 22, 2018.
  • Hoffer EK. Imaging in Deep Venous Thrombosis of the Lower Extremity. In: Imaging in Deep Venous Thrombosis of the Lower Extremity. New York, NY: WebMD. http://emedicine.medscape.com/article/420457. Updated December 20, 2015. Accessed February 13, 2017.
  • Le T, Bhushan V, Bagga HS. First Aid for the USMLE Step 2 CK. McGraw-Hill Medical; 2009.
  • Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education; 2015.
  • Agabegi SS, Agabegi ED. Step-Up To Medicine. Baltimore, MD, USA: Lippincott Williams & Wilkins; 2013.
  • 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.
last updated 11/02/2020
{{uncollapseSections(['DWa1nj', 'M41MPS0', 'xWaEnj', 'yWadLj', 'AWaRLj', 'aJ1Qs30', '-WaDLj', '0daeoj', 'gq1FB30', 'adaQoj', 'iJ1JF30', 'Xda9oj', '_Wa5Lj', 'Ydanoj', '841OOS0'])}}