Acta Scientific Medical Sciences (ISSN: 2582-0931)

Review Artilce Volume 4 Issue 3

Evidence-Based Novel Management Options of Acute Deep Vein Thrombosis (DVT) and Prevention of DVT Recurrence in Primary Care Medicine Anno 2018 - 2020

Jan Jacques Michiels1,2,3*, Wim Moossdorff1, Rob Strijkers1, Mildred U Lao1, Hans Smeets1, Ming Han1, Wilfried Schroyens2 and Alain Gadisseur2

1Primary Care Medicine Star-Medical Diagnostic Center, Rotterdam, the Netherlands
2Hemostasis Research Unit, Department of Hematology, University Hospital Antwerp, Antwerp Belgium
3Goodheart Institute in Nature Medicine, Blood Coagulation and Vascular Medicine Science Center, Rotterdam, the Netherlands

*Corresponding Author: Jan Jacques Michiels, Primary Care Medicine Star-Medical Diagnostic Center, Rotterdam, the Netherlands.

Received: February 05, 2020; Published: February 14, 2020



  Complete compression ultrasonography (CCUS) rules in and out acute deep vein thrombosis (DVT) and picks up alternative diagnoses (AD) including Baker’s cyst, muscle hematomas, old DVT, and superficial vein thrombosis. CCUS from the ileofemoral region to the popliteal and calf veins has become the objective test in routine daily practice to diagnose acute DVT and to classify distal, proximal and inguinal Leg Extremity Thrombosis (LET class I, II and III DVT) extension.

  Acute DVT patients are recommended to wear medical elastic stockings (MECS) for symptomatic relief of swollen legs for a few weeks. Objective testing with colour duplex ultrasonography (DUS) at time points 1, 3 and 6 months post-DVT for residual vein thrombosis is of critically importance to assess the risk for DVT recurrence and post-thrombotic syndrome (PTS) evolution. Prospective studies clearly indicate that MECS only relieves subjective symptoms of PTS but do not reduce DVT recurrence and do not improve the objective signs of PTS after long-term and lifelong follow-up.

  Rapid and complete recanalization on DUS within 1 to 3 months post-DVT is associated with no reflux and low risk on DVT and PTS on the basis of which MECS and anticoagulation with vitamin K antagonist or Direct Oral anti-Xa or IIa Coagulant (DOAC) inhibitor can be withhold at 3 months post-DVT. Delayed recanalisation with residual vein thrombosis (RVT) on DUS at 3 months post-DVT is assocated with reflux due to valve destruction and a high risk of DVT recurrence and PTS indicating the need to extend anticoagulation for 6 momths to 1 year in the absence of PTS and for 2 years in the presence of PTS.

  Direct Anticoagulants: DOACs preferentially apixaban twice daily have become the first line treatment option of acute DVT and PE for effective reduction of venous thromboembolism (VTE). Apixaban BID is superior to rivaroxaban OD for 3 to 6 months acute DVT/PE treatment in terms of significantly less major bleeds (MB) clinical relevant non-major (CRNM) bleeds. Low dose apixaban BID daily is the treatment of choice for extended anticoagulation in post-DVT patients at high risk of DVT recurrence. Patients with acute DVT in the ileofemoral veins are at highest risk of DVT recurrence. Catheter Directed Thrombolysis (CDT) on top of anticoagulation for the invasive treatment of acute iliofemoral deep-vein thrombosis compared with standard anticoagulant therapy (vitamine K antagnist or DOAC) alone is noninferior and absolutely not superior in terms of post-thrombotic syndrome sequelae after 1 year.

  A prospective safety-efficacy DVT-PTS Bridging the Gap management study is proposed in patients with a first distal, proximal and iliofemoral thrombosis to reduce the overall DVT recurrence rate from about 30% to less than 5% patient/years to prevent PTS significantly during long-term follow-up.

Keywords: Deep Vein Thrombosis; DVT Recurrence; Posthrombotic Syndrome; D-Dimer; Compression Ultrosonography; Colour Ultrasonography; Anticoagulation; Catheter Directed Thrombolysis; Vitamin K Antagonist; Direct Oral Anticoagulants; DOAC



  1. Michiels JJ., et al. “Safe exclusion of deep vein thrombosis (DVT) by a rapid sensitive ELISA D-dimer and compression ultrasonography in 1330 outpatients with suspected DVT”. Angiology Ahead of Publication (2016).
  2. Michiels JJ., et al. “Duplex ultrasound, clinical score, thrombotic risk, and D-dimer testing for evidence based diagnosis and management of deep vein thrombosis and alternative diagnosis in the orimary care setting and outpatient ward”. International Angiology 33.1 (2014): 1-19.
  3. Lensing AW., et al. “Detection of deep vein thrombosis by real-time B-mode ultrasonography”. The New England Journal of Medicine 320 (1989): 342-345.
  4. Cogo A., et al. “Compression ultra¬sonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study”. British Medical Journal 316 (1998): 17-20.
  5. Birdwell BG., et al. “Theclinical validity of normal compression ultrasonography in outpatients suspected of havinh deep vein thrombosis”. Annals of Internal Medicine 128 (1998): 1-7.
  6. Michiels JJ., et al. “Different accuracies of rapid enzyme-limked immunosorbeny, turbidimetric D-dimer asays for thrombosis exclusion: impact on diagnostic work-up of outpatients with suspected deep vein thrombosis and pulmonary embolism”. Sem Thromb Hemotas 32 (2006): 687-693. 
  7. Schellong SM., et al. “Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis”. Thromb Haemost 89.2 (2003): 228-234.
  8. Palareti G and Schellong S. “Isolated distal deep vein thrombosis: what we know and what we are doing”. Journal of Thrombosis and Haemostasis 10 (2012): 11-19.
  9. Eklöf B., et al. “American Venous Forum International Ad Hoc Committee for Revision of the CEAP Classification. Revision of the CEAP classification for chronic venous disorders: consensus statement”. Journal of Vascular Surgery 40.6 (2004): 1248-1252.
  10. Labropoulos N., et al. “The effect of venous thrombus location and the extent on the development of post-thrombotic signs and symptoms”. Journal of Vascular Surgery 48.2 (2008): 407-412.
  11. Prandoni P., et al. “The clinical course of deep vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients”. Haematologica 82 (1997): 423-428.
  12. Pesavento R., et al. “Postthrombotic syndrome”. Seminars in Thrombosis and Hemostasis 32.7 (2006): 744-751.
  13. Michiels JJ., et al. “Prospective Studies on Diagnosis, Prevention, and Management of Deep Vein Thrombosis (DVT), DVT Recurrence and the Post-Thrombotic Syndrome (PTS): From Concept to Study Design in the Primary Care Setting”. Family Medicine and Medical Science Research 3 (2014): 138. 
  14. Michiels JJ., et al. “Complete Compression Ultrsonography, Clinical Score, Underlying Risk Factors and D-Dimer Testing for Objective Evidence Based Diagnosis and Exclusion of Deep Vein Thrombosis and Alternative Diagnoses in the Primary Care and Hospital Setting”. Journal of Hematology and Thromboembolic Diseases (2015): 3-2.
  15. Aschwanden M., et al. “Effect of prolonged treatment with compression stockings to prevent post0thrombotic sequelae: a randomized controlledtrial”. Journal of Vascular Surgery 47 (2008): 1015-1021.
  16. Brandjes DP., et al. “Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis”. Lancet 349.9054 (1997): 759-762.
  17. Prandoni P., et al. “Below-knee elastic compres¬sion stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial”. Annals of Internal Medicine 141.4 (2004): 249-256.
  18. Kahn SR., et al. “SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a ran¬domised placebo-controlled trial”. Lancet 383.9920 (2014): 880-888.
  19. Arnoldussen CWKP and Wittens CHA. “An imaging approach to deep vein thrombosis and the lower extremity thrombosis classification”. Phlebology 27.1 (2012):143-148.
  20. De Maeseneer MGR., et al. “Analysis of 1338 patients with acute lower limb deep vein thrombosis (DVT) supports the inadequacy of the term ‘proximal DVT”. European Journal of Vascular and Endovascular Surgery (2015).
  21. Strijkers R., et al. “Validation of the LET classification. Thesis: Safety and feasibility of ultrasound accelerated cathether directed thrombolysis and the postthrombotic syndrome”. Thesis 2016 Chapter 4 51-61.
  22. Strijkers RHW., et al. “Proximal extension of deep vein thrombosis: does it predict postthrombotic syndrome and quality of life at long term. Thesis 2016: Safety and feasibility of ultrasound accelerated cathether directed thrombolysis and the postthrombotic syndrome”. Chapter 5 63-79.
  23. Palareti G., et al. “PROLONG Investigators. Simplify D-dimer testing to determine the duration of anticoagulation therapy”. The New England Journal of Medicine 355 (2006): 1780-1789. 
  24. Palareti G., et al. “D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a manage¬ment study”. Blood 124.2 (2014):196-203.
  25. Siragusa S., et al. “Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Com-pression UltraSonography (DACUS) study”. Blood 112.3 (2008): 511-515. 
  26. Siragusa S., et al. “Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein throm¬bosis of the lower limbs: the extended DACUS study”. American Journal of Hematology 86.11 (2011): 914-917. 
  27. Lagerstet CI., et al. “Need for long-term anticoagulant treatment of symptomatic cakf vein thrombosis”. Lancet 2 (1985): 515-518.
  28. Palareti G. “How I teat isolated distal deep vein thrombosis (IDDVT)”. Blood 123.12 (2014): 1802-1809.
  29. Notten P., et al. “Ultrasound-accelerated cathether-directed thrombolysis versus anticoagulation (CAVA) for the prevention of postthrombotic syndrome (PTS): a single-blind multicenter, randomized trial”. The Lancet Haematology 7 (2020): e40-e49. 
  30. Agnelli G., et al. “Oral apixaban for fort he treatment of acute venous thromboembolism”. The New England Journal of Medicine 369 (2013): 799-808.
  31. Agnelli G., et al. “Apixaban for extended treatment of venous embolism”. The New England Journal of Medicine 368 (2013):  699-708. 
  32. EINSTEIN Investigators., et al. “Oral rivaroxaban for symptomatic venous thromboembolism”. The New England Journal of Medicine 363 (2010): 2499-2510.
  33. EINSTEIN-PE Investigators., et al. “Oral rivaroxaban fort he treatment of symptomatic pulmonary emboilsm”. The New England Journal of Medicine 366 (2012): 1287-1297.
  34. Schulman S., et al. “Dabigatran versus warfarin in the treatment of acute venous thromboemboilsm”. The New England Journal of Medicine 361 (2009): 2342-2352.
  35. Schulman S., et al. “Extended use of dabigatran, warfarin or placebo in venous thromboembolism”. The New England Journal of Medicine 368 (2013): 709-717.
  36. Hokusai-VTE Investigators., et al. “Endoxaban versus warfarin fort he treatment of symptomatic venous thromboembolism”. The New England Journal of Medicine 369 (2013): 1406-1415.
  37. Schulman S., et al. “Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis”. Circulation 129 (2014): 764-772.
  38. Van Es N., et al. “Direct oral anticoagulants for acute venous thromboembolism: evidence from phase 3 trials”. Blood 124 (2014): 1968-1975.
  39. Cohen A., et al. “Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results”. Advances in Therapy 31 (2014): 473-493.
  40. Cohen AT., et al. “Comparison of the Direct Oral Anti Coagulants (DOACs) apixaban, dabigatran and rivaroxaban in the extended treatment and prevention of VTE: systemic review and Network meta-analysis”. Plos One 11.8 160-064.
  41. Mantha S and Ansell J. “Indiret comparison of dabigatran, rivaroxaban, apixaban and endoxaban for the treatment of acute venous thromboembolism”. Journal of Thrombosis and Thrombolysis 39 (2015): 155-165.
  42. Baker WL and Phung QJ. “Systemic review and adjusted indirect comparison of oral anticoagulants in atrial fibrillation”. Circulation: Cardiovascular Quality and Outcomes 5.5 (2012): 711-719.
  43. Halvorson S., et al. “A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulation”. European Heart Journal - Cardiovascular Pharmacotherapy (2017):10.109.
  44. Lamberts M., et al. “Major Bleeding Complications and Persistence With Oral Anticoagulation in Non-Valvular Atrial Fibrillation: Contemporary Findings in Real-Life Danish Patients”. Journal of the American Heart Association 6 (2017): e004517. 
  45. Michiels JJ., et al. “Diagnosis of deep vein thrombosis (DVT) and prevention of DVT recurrence and the post-thrombotic syndrome in the parimary care medicine setting anno 2014”. World Journal of Critical Care Medicine 4.1 (2015): 29-39.
  46. Michiels JJ., et al. “Novel evidence-based diagnosis and management og lower extremity deep vein thrombosis (DVT), prevention of DVT recurrence and the postthrombotic syndrome: personal experiences and critical appraisal of the literature 1998-2018”. Family Medicine and Medical Science Research 7 (2018): 2.


Citation: Jan Jacques Michiels., et al. “Evidence-Based Novel Management Options of Acute Deep Vein Thrombosis (DVT) and Prevention of DVT Recurrence in Primary Care Medicine Anno 2018 - 2020". Acta Scientific Medical Sciences 4.3 (2020): 89-101.


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