Vol 7, No 3 (2016)
Review paper
Published online: 2017-02-23

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Venous thromboembolism — practical aspects of treatment

Krystyna Zawilska, Klaudia Zawilska
Hematologia 2016;7(3):231-242.


Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence due to population aging. The treatment of VTE is undergoing tremendous changes with the introduction of direct oral anticoagulants (DOAC), therefore clinicians need to understand the new treatment paradigms. The DOAC include dabigatran, which inhibits thrombin, and ri­varoxaban, apixaban and edoxaban, which inhibit factor Xa. When compared with conventional VTE treatment consisting of a parenteral anticoagulant followed by a vitamin K antagonist, the DOAC were equally effective for prevention of recurrence, but were associated with less bleeding. This paper identifies VTE patients, who are or are not candidates for DOAC, provides guidance on how to choose among DOAC, discusses the optimal treatment duration for VTE and finally, reviews the management of bleeding, including the role of specific reversal agents. Furthemore, this article provides clinical guidance, based on the newest existing guidelines and consensus expert opinion, on the management of patients presenting with cancer-associated VTE, patients with VTE and thrombocytopenia or renal insufficiency, as well as patients with venous thrombosis in unusual sites, such as splanchnic vein thrombosis, cerebral vein thrombosis and retinal vein occlusion.

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  1. Cohen AT, Agnelli G, Anderson FA, et al. VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007; 98(4): 756–764.
  2. ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to the global disease burden. J Thromb Haemost. 2014; 12(10): 1580–1590.
  3. Kearon C, Akl EA, Comerota AJ, et al. American College of Chest Physicians. 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): e419S–e494S.
  4. Polskie wytyczne profilaktyki i leczenia żylnej choroby zakrzepowo-zatorowej: aktualizacja 2012. Med. Prakt. 2012. Wyd. specj.: Żylna choroba zakrzepowo-zatorowa. 2012.
  5. Zawilska K, Bała MM, Błędowski P, et al. Working Group fom the Anticoagulation and Thrombolytic ACCP Conference. Polish guidelines for the prevention and treatment of venous thromboembolism. 2012 update. Pol Arch Med Wewn. 2012; 122 Suppl 2: 3–74.
  6. Zawilska K. Żylna choroba zakrzepowo-zatorowa. In: Robak T, Warzocha K. ed. Hematologia. Via Medica, Gdańsk 2016: 507–521.
  7. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016; 149(2): 315–352.
  8. van der Hulle T, Kooiman J, den Exter PL, et al. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2014; 12(3): 320–328.
  9. Weitz J, Jaffer I. Optimizing the safety of treatment for venous thromboembolism in the era of the direct oral anticoagulants. Pol. Arch. Med. Wewn. . 2016; 126: 1–8.
  10. Marlu R, Hodaj E, Paris A, et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012; 108(2): 217–224.
  11. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015; 373(6): 511–520.
  12. Glund S, Moschetti V, Norris S, et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015; 113(5): 943–951.
  13. Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015; 386(9994): 680–690.
  14. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015; 373(25): 2413–2424.
  15. Connors JM. Antidote for Factor Xa Anticoagulants. N Engl J Med. 2015; 373(25): 2471–2472.
  16. Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014; 371(22): 2141–2142.
  17. Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res. 2010; 125(6): 490–493.
  18. Khorana AA. Cancer-associated thrombosis: updates and controversies. Hematology Am Soc Hematol Educ Program. 2012; 2012: 626–630.
  19. Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013; 11(1): 56–70.
  20. Khorana AA, Carrier M, Garcia DA, et al. Guidance for the prevention and treatment of cancer-associated venous thromboembolism. J Thromb Thrombolysis. 2016; 41(1): 81–91.
  21. Zawilska K. Profilaktyka i leczenie żylnych powikłań zakrzepowo-zatorowych u pacjentów z chorobą nowotworową. Hematologia. 2014; 5: 228–238.
  22. Wojtukiewicz M, Sierko E, Tomkowski W, et al. Guidelines for the prevention and treatment of venous thromboembolism in patients with cancers treated conservatively. Onkologia Clin Pract. 2016; 12: 67–91.
  23. Vedovati MC, Germini F, Agnelli G, et al. Direct oral anticoagulants in patients with VTE and cancer: a systematic review and meta-analysis. Chest. 2015; 147(2): 475–483.
  24. Lee AYY, Levine MN, Baker RI, et al. Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003; 349(2): 146–153.
  25. Lee AYY, Kamphuisen PW, Meyer G, et al. CATCH Investigators. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA. 2015; 314(7): 677–686.
  26. Short NJ, Connors JM. New oral anticoagulants and the cancer patient. Oncologist. 2014; 19(1): 82–93.
  27. O'Connell C, Razavi P, Ghalichi M, et al. Unsuspected pulmonary emboli adversely impact survival in patients with cancer undergoing routine staging multi-row detector computed tomography scanning. J Thromb Haemost. 2011; 9(2): 305–311.
  28. Murchison JT, Wylie L, Stockton DL. Excess risk of cancer in patients with primary venous thromboembolism: a national, population-based cohort study. Br J Cancer. 2004; 91(1): 92–95.
  29. Watson HG, Keeling DM, Laffan M, et al. British Committee for Standards in Haematology. Guideline on aspects of cancer-related venous thrombosis. Br J Haematol. 2015; 170(5): 640–648.
  30. Enden T, Haig Y, Kløw NE, et al. CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012; 379(9810): 31–38.
  31. Meissner MH, Gloviczki P, Comerota AJ, et al. Society for Vascular Surgery, American Venous Forum. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2012; 55(5): 1449–1462.
  32. Kahn SR, Comerota AJ, Cushman M, et al. American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014; 130(18): 1636–1661.
  33. Ageno W, Beyer-Westendorf J, Garcia DA, et al. Guidance for the management of venous thrombosis in unusual sites. J Thromb Thrombolysis. 2016; 41(1): 129–143.
  34. Konstantinides SV, Torbicki A, Agnelli G, et al. Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014; 35(43): 3033–69, 3069a.
  35. Brighton TA, Eikelboom JW, Mann K, et al. ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012; 367(21): 1979–1987.
  36. Andreozzi GM, Bignamini AA, Davì G, et al. SURVET Study Investigators. Sulodexide for the Prevention of Recurrent Venous Thromboembolism: The Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Circulation. 2015; 132(20): 1891–1897.
  37. Kyrle PA. How I treat recurrent deep-vein thrombosis. Blood. 2016; 127(6): 696–702.

Hematology in Clinical Practice