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Prevention and Treatment of Venous Thromboembolism in Patients with Cancer: Focus on Drug Therapy

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Abstract

Venous thromboembolism (VTE) is a frequent complication in patients with cancer and is associated with significant morbidity and mortality. The use of anticoagulants for the prevention and treatment of VTE in this population is challenging given the high risk of both recurrent VTE and bleeding complications. Thromboprophylaxis with subcutaneous low-molecular-weight heparin (LMWH) is recommended in cancer patients hospitalized for an acute medical illness and in those undergoing major surgery. In ambulatory cancer patients with or without central venous catheters, routine thromboprophylaxis is not recommended because of the relatively low benefit-to-risk ratio. To identify cancer outpatients at very high risk of VTE who may benefit from thromboprophylaxis, VTE risk stratification tools based on tumour type, clinical parameters, or coagulation biomarkers have been proposed, but their clinical utility needs validation. The mainstay of treatment for cancer-associated VTE is LMWH for at least 6 months or longer in case of active disease. The same initial and long-term treatment for incidental VTE as for symptomatic VTE can be suggested while awaiting additional studies in this area.

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References

  1. Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood. 2013;122:1712–23.

    Article  CAS  PubMed  Google Scholar 

  2. Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293:715–22.

    Article  CAS  PubMed  Google Scholar 

  3. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case–control study. Arch Intern Med. 2000;160:809–15.

    Article  CAS  PubMed  Google Scholar 

  4. Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer—a cohort study using linked United Kingdom databases. Eur J Cancer. 2013;49:1404–13.

    Article  PubMed  Google Scholar 

  5. van Es N, Bleker SM, Di Nisio M. Cancer-associated unsuspected pulmonary embolism. Thromb Res. 2014;133(Suppl):S172–8.

    PubMed  Google Scholar 

  6. Ageno W, Dentali F, Squizzato A. How I treat splanchnic vein thrombosis. Blood. 2014;124:3685–91.

    Article  CAS  PubMed  Google Scholar 

  7. Lamontagne F, McIntyre L, Dodek P, et al. Nonleg venous thrombosis in critically ill adults. JAMA Intern Med. 2014;174(5):689.

    Article  PubMed  Google Scholar 

  8. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5:632–4.

    Article  CAS  PubMed  Google Scholar 

  9. Gussoni G, Frasson S, La Regina M, Di Micco P, Monreal M. Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry. Thromb Res. 2013;131:24–30.

    Article  CAS  PubMed  Google Scholar 

  10. Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Büller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol. 2000;18:3078–83.

    CAS  PubMed  Google Scholar 

  11. Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100:3484–8.

    Article  CAS  PubMed  Google Scholar 

  12. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146–53.

    Article  CAS  PubMed  Google Scholar 

  13. Francis CW, Kessler CM, Goldhaber SZ, Kovacs MJ, Monreal M, Huisman MV, et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost. 2015;13:1028–35.

    Article  CAS  PubMed  Google Scholar 

  14. Deitcher SR, Kessler CM, Merli G, Rigas JR, Lyons RM, Fareed J. Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period. Clin Appl Thromb Hemost. 2006;12:389–96.

    Article  CAS  PubMed  Google Scholar 

  15. Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, et al. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer. JAMA. 2015;314:677.

    Article  CAS  PubMed  Google Scholar 

  16. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(Suppl):S49–55.

    Article  CAS  PubMed  Google Scholar 

  17. Donato J, Campigotto F, Uhlmann EJ, et al. Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study. Blood. 2015;126(4):494–9.

    Article  CAS  PubMed  Google Scholar 

  18. Van Cutsem E, Arends J. The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9:S51–63.

    Article  PubMed  Google Scholar 

  19. 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;124:1968–75.

    Article  PubMed  Google Scholar 

  20. Lee AYY, Carrier M. Treatment of cancer-associated thrombosis: perspectives on the use of novel oral anticoagulants. Thromb Res. 2014;133(Suppl):S167–71.

    Article  CAS  PubMed  Google Scholar 

  21. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003;90:446–55.

    CAS  PubMed  Google Scholar 

  22. Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005;92:1212–20.

    Article  CAS  PubMed  Google Scholar 

  23. Akl EA, Kahale LA, Sperati F, Neumann I, Labedi N, Terrenato I, et al. Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer. Cochrane Database Syst Rev. 2014;168:CD009447.

    Google Scholar 

  24. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e227S–77S.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2189–204.

    Article  CAS  PubMed  Google Scholar 

  26. Bergqvist D, Agnelli G, Cohen AT, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002;346(13):975–80.

  27. ENOXACAN Study Group. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg. 1997;84:1099–103.

    Article  Google Scholar 

  28. Sakon M, Kobayashi T, Shimazui T. Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: results from a multicenter, randomized, open-label study. Thromb Res. 2010;125:e65–70.

    Article  CAS  PubMed  Google Scholar 

  29. Akl EA, Terrenato I, Barba M, Sperati F, Muti P, Schünemann HJ. Extended perioperative thromboprophylaxis in patients with cancer: a systematic review. Thromb Haemost. 2008;100:1176–80.

    CAS  PubMed  Google Scholar 

  30. Kakkar VV, Balibrea JL, Martínez-González J, Prandoni P, CANBESURE Study Group. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. J Thromb Haemost. 2010;8:1223–9.

    Article  CAS  PubMed  Google Scholar 

  31. Francis CW. Prevention of venous thromboembolism in hospitalized patients with cancer. J Clin Oncol. 2009;27:4874–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8:2450–7.

    Article  CAS  PubMed  Google Scholar 

  33. Spyropoulos AC, Anderson FA, FitzGerald G, Decousus H, Pini M, Chong BH, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706–14.

    Article  PubMed  Google Scholar 

  34. Kucher N, Koo S, Quiroz R, et al. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med. 2005;352(10):969–77.

  35. Carrier M, Khorana AA, Moretto P, Le Gal G, Karp R, Zwicker JI. Lack of evidence to support thromboprophylaxis in hospitalized medical patients with cancer. Am J Med. 2014;127(82–6):e1.

    PubMed  Google Scholar 

  36. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, 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:e419S–94S.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Easaw JC, Shea-Budgell MA, Wu CMJ, Czaykowski PM, Kassis J, Kuehl B, et al. Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis. Curr Oncol. 2015;22:133–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Streiff MB, Holmstrom B, Ashrani A, Bockenstedt PL, Chesney C, Eby C, et al. Cancer-associated venous thromboembolic disease, Version 1.2015. J Natl Compr Canc Netw. 2015;13:1079–95.

    PubMed  Google Scholar 

  39. Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011;365:2167–77.

    Article  CAS  PubMed  Google Scholar 

  40. Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368:513–23.

    Article  CAS  PubMed  Google Scholar 

  41. DiNisio M, Porreca E, Otten H-M, Rutjes AW. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2014;8:CD008500.

    Google Scholar 

  42. Pelzer U, Opitz B, Deutschinoff G, et al. Efficacy of prophylactic low-molecular weight heparin for ambulatory patients with advanced pancreatic cancer: outcomes from the CONKO-004 Trial. J Clin Oncol. 2015;33(18):2028–34.

  43. Maraveyas A, Waters J, Roy R, Fyfe D, Propper D, Lofts F, et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer. 2012;48:1283–92.

    Article  CAS  PubMed  Google Scholar 

  44. Vadhan-Raj S, Zhou X, Varadhachary GR, Milind J, Fogelmann D, Shroff D, et al. Randomized controlled trial of dalteparin for primary thromboprophylaxis for venous thromboembolism (VTE) in patients with advanced pancreatic cancer: risk factors predictive of VTE. 55th Annu Meet Am Soc Hematol ASH 2013 New Orleans. 2013.

  45. Haas SK, Freund M, Heigener D, Heilmann L, Kemkes-Matthes B, von Tempelhoff G-F, et al. Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer. Clin Appl Thromb Hemost. 2012;18:159–65.

    Article  CAS  PubMed  Google Scholar 

  46. Perry JR, Julian JA, Laperriere NJ, Geerts W, Agnelli G, Rogers LR, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost. 2010;8:1959–65.

    Article  CAS  PubMed  Google Scholar 

  47. De Stefano V, Za T, Rossi E. Venous thromboembolism in multiple myeloma. Semin Thromb Hemost. 2014;40:338–47.

    Article  PubMed  Google Scholar 

  48. Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, et al. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012;119:933–9.

    Article  CAS  PubMed  Google Scholar 

  49. Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011;29:986–93.

    Article  CAS  PubMed  Google Scholar 

  50. Levine MN, Gu C, Liebman HA, Escalante CP, Solymoss S, Deitchman D, et al. A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer. J Thromb Haemost. 2012;10:807–14.

    Article  CAS  PubMed  Google Scholar 

  51. Thaler J, Ay C, Pabinger I. Venous thromboembolism in cancer patients - risk scores and recent randomised controlled trials. Thromb Haemost. 2012;108:1042–8.

    Article  PubMed  Google Scholar 

  52. Hisada Y, Geddings JE, Ay C, Mackman N. Venous thrombosis and cancer: from mouse models to clinical trials. J Thromb Haemost. 2015;13:1372–82.

    Article  CAS  PubMed  Google Scholar 

  53. Zwicker JI, Liebman HA, Bauer KA, Caughey T, Campigotto F, Rosovsky R, et al. Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study). Br J Haematol. 2013;160:530–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Ay C, Dunkler D, Marosi C, Chiriac A-L, Vormittag R, Simanek R, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377–82.

    Article  CAS  PubMed  Google Scholar 

  55. Grant JD, Stevens SM, Woller SC, Lee EW, Kee ST, Liu DM, et al. Diagnosis and management of upper extremity deep-vein thrombosis in adults. Thromb Haemost. 2012;108:1097–108.

    Article  PubMed  Google Scholar 

  56. Akl EA, Kamath G, Yosuico V, Kim SY, Barba M, Sperati F, et al. Thromboprophylaxis for patients with cancer and central venous catheters: a systematic review and a meta-analysis. Cancer. 2008;112:2483–92.

    Article  CAS  PubMed  Google Scholar 

  57. Mandalà M, Falanga A, Roila F. Management of venous thromboembolism (VTE) in cancer patients: ESMO clinical practice guidelines. Ann Oncol. 2011;22(Suppl 6):vi85–92.

  58. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e195S–226S.

  59. Akl EA, Kahale LA, Neumann I, Barba M, Sperati F, Terrenato I, et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev. 2014;136:CD006649.

    Google Scholar 

  60. van Doormaal FF, Raskob GE, Davidson BL, Decousus H, Gallus A, Lensing AW, et al. Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. Thromb Haemost. 2009;101:762–9.

    PubMed  Google Scholar 

  61. National Comprehensive Cancer Network. Cancer-associated venous thromboembolic disease [Internet]. [cited 2015 Jul 22]. Available from: https://www.nccn.org/professionals/physician_gls/pdv/vte.pdf.

  62. Konstantinides S V, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35:3033–69, 3069a–3069k.

  63. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106:2710–5.

    Article  CAS  PubMed  Google Scholar 

  64. Akl EA, Kahale L, Barba M, Neumann I, Labedi N, Terrenato I, et al. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane database Syst Rev. 2014;7:CD006650.

    PubMed  Google Scholar 

  65. Easaw JC, Shea-Budgell MA, Wu CMJ, Czaykowski PM, Kassis J, Kuehl B, et al. Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment. Curr Oncol. 2015;22:144–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, et al. Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost. 2015;114:1–8.

    Article  Google Scholar 

  67. Kleinjan A, Aggarwal A, Van de Geer A, Faselis C, Büller HR, Di Nisio M, et al. A worldwide survey to assess the current approach to the treatment of patients with cancer and venous thromboembolism. Thromb Haemost. 2013;110:1–7.

    Article  Google Scholar 

  68. Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost. 2013;11:1760–5.

    Article  CAS  PubMed  Google Scholar 

  69. den Exter PL, Hooijer J, Dekkers OM, Huisman MV. Risk of recurrent venous thromboembolism and mortality in patients with cancer incidentally diagnosed with pulmonary embolism: a comparison with symptomatic patients. J Clin Oncol. 2011;29:2405–9.

    Article  Google Scholar 

  70. Sahut D’Izarn M, Caumont Prim A, Planquette B, Revel MP, Avillach P, Chatellier G, et al. Risk factors and clinical outcome of unsuspected pulmonary embolism in cancer patients: a case–control study. J Thromb Haemost. 2012;10:2032–8.

    Article  PubMed  Google Scholar 

  71. Shinagare AB, Okajima Y, Oxnard GR, Dipiro PJ, Johnson BE, Hatabu H, et al. Unsuspected pulmonary embolism in lung cancer patients: comparison of clinical characteristics and outcome with suspected pulmonary embolism. Lung Cancer. 2012;78:161–6.

    Article  PubMed Central  PubMed  Google Scholar 

  72. O’Connell C, Razavi P, Ghalichi M, Boyle S, Vasan S, Mark L, 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;9:305–11.

    Article  PubMed  Google Scholar 

  73. Browne AM, Cronin CG, English C, NiMhuircheartaigh J, Murphy JM, Bruzzi JF. Unsuspected pulmonary emboli in oncology patients undergoing routine computed tomography imaging. J Thorac Oncol. 2010;5:798–803.

    Article  PubMed  Google Scholar 

  74. Storto ML, Di Credico A, Guido F, Larici AR, Bonomo L. Incidental detection of pulmonary emboli on routine MDCT of the chest. AJR Am J Roentgenol. 2005;184:264–7.

    Article  PubMed  Google Scholar 

  75. Gladish GW, Choe DH, Marom EM, Sabloff BS, Broemeling LD, Munden RF. Incidental pulmonary emboli in oncology patients: prevalence, CT evaluation, and natural history. Radiology. 2006;240:246–55.

    Article  PubMed  Google Scholar 

  76. Sun J-M, Kim TS, Lee J, Park YH, Ahn JS, Kim H, et al. Unsuspected pulmonary emboli in lung cancer patients: the impact on survival and the significance of anticoagulation therapy. Lung Cancer. 2010;69:330–6.

    Article  PubMed  Google Scholar 

  77. Menapace LA, Peterson DR, Berry A, Sousou T, Khorana AA. Symptomatic and incidental thromboembolism are both associated with mortality in pancreatic cancer. Thromb Haemost. 2011;106:371–8.

    Article  CAS  PubMed  Google Scholar 

  78. Soler S, Delgado C, Ballaz A, Cisneros E, Malý R, Babalis D, et al. Unsuspected pulmonary embolism in patients with cancer. Thromb Res. 2012;129(Suppl):S16–9.

    Article  CAS  PubMed  Google Scholar 

  79. van der Hulle T, den Exter PL, Planquette B, Meyer G, Soler S, Monreal M, et al. Risk of recurrent venous thromboembolism and major haemorrhage in cancer-associated incidental pulmonary embolism amongst treated and untreated patients: a pooled analysis of 926 patients. J Thromb Haemost. 2015;124:590.

    Google Scholar 

  80. den Exter PL, van Es J, Klok FA, Kroft LJ, Kruip MJHA, Kamphuisen PW, et al. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood. 2013;122:1144–9.

    Article  Google Scholar 

  81. Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res. 2010;126:e266–70.

  82. Thatipelli MR, McBane RD, Hodge DO, Wysokinski WE. Survival and recurrence in patients with splanchnic vein thromboses. Clin Gastroenterol Hepatol. 2010;8:200–5.

    Article  PubMed  Google Scholar 

  83. Condat B, Pessione F, Hillaire S, Denninger MH, Guillin MC, Poliquin M, et al. Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology. 2001;120:490–7.

    Article  CAS  PubMed  Google Scholar 

  84. Spaander MCW, Hoekstra J, Hansen BE, Van Buuren HR, Leebeek FWG, Janssen HLA. Anticoagulant therapy in patients with non-cirrhotic portal vein thrombosis: effect on new thrombotic events and gastrointestinal bleeding. J Thromb Haemost. 2013;11:452–9.

    Article  CAS  PubMed  Google Scholar 

  85. Plessier A, Darwish-Murad S, Hernandez-Guerra M, Consigny Y, Fabris F, Trebicka J, et al. Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study. Hepatology. 2010;51:210–8.

    Article  PubMed  Google Scholar 

  86. Amitrano L, Guardascione MA, Scaglione M, Pezzullo L, Sangiuliano N, Armellino MF, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol. 2007;102:2464–70.

    Article  PubMed  Google Scholar 

  87. Amitrano L, Guardascione MA, Menchise A, Martino R, Scaglione M, Giovine S, et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol. 2010;44:448–51.

    CAS  PubMed  Google Scholar 

  88. Ageno W, Riva N, Schulman S, et al. Long-term clinical outcomes of splanchnic vein thrombosis. JAMA Intern Med. 2015;175(9):1474.

  89. Lee AYY, Levine MN, Butler G, Webb C, Costantini L, Gu C, et al. Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. J Clin Oncol. 2006;24:1404–8.

    Article  PubMed  Google Scholar 

  90. Kovacs MJ, Kahn SR, Rodger M, Anderson DR, Andreou R, Mangel JE, et al. A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without catheter removal for the treatment of upper extremity deep vein thrombosis (The Catheter Study). J Thromb Haemost. 2007;5:1650–3.

    Article  CAS  PubMed  Google Scholar 

  91. Delluc A, Le Gal G, Scarvelis D, Carrier M. Outcome of central venous catheter associated upper extremity deep vein thrombosis in cancer patients. Thromb Res. 2015;135:298–302.

    Article  CAS  PubMed  Google Scholar 

  92. Lopaciuk S, Bielska-Falda H, Noszczyk W, Bielawiec M, Witkiewicz W, Filipecki S, et al. Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis. Thromb Haemost. 1999;81:26–31.

    CAS  PubMed  Google Scholar 

  93. López-Beret P, Orgaz A, Fontcuberta J, Doblas M, Martinez A, Lozano G, et al. Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis. J Vasc Surg. 2001;33:77–90.

    Article  PubMed  Google Scholar 

  94. Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002;162:1729–35.

    Article  CAS  PubMed  Google Scholar 

  95. Cesarone M, Ledda A, Nicolaides A, Belcaro G, Geroulakos G. Three-month, outpatient, oral anticoagulant treatment in comparison with low-molecular-weight heparin in cancer patients. Circulation. 2003;108:2875.

    Google Scholar 

  96. Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, et al. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006;119:1062–72.

    Article  CAS  PubMed  Google Scholar 

  97. Romera A, Cairols MA, Vila-Coll R, Martí X, Colomé E, Bonell A, et al. A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis. Eur J Vasc Endovasc Surg. 2009;37:349–56.

    Article  CAS  PubMed  Google Scholar 

  98. van Doormaal FF, Cohen AT, Davidson BL, Decousus H, Gallus AS, Gent M, et al. Idraparinux versus standard therapy in the treatment of deep venous thrombosis in cancer patients: a subgroup analysis of the Van Gogh DVT trial. Thromb Haemost. 2010;104:86–91.

    Article  PubMed  Google Scholar 

  99. Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366(7):601–9.

    Article  CAS  PubMed  Google Scholar 

  100. Agnelli G, Gussoni G, Bianchini C, et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009;10(10):943-9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

    Nick van Es & Suzanne M. Bleker

  2. Department of Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands

    Ineke T. Wilts

  3. Dipartimento di Medicina e Scienze dell’Invecchiamento, Gabriele D’Annunzio University, Chieti, Italy

    Ettore Porreca

  4. Department of Medical, Oral and Biotechnological Sciences, Gabriele D’Annunzio University, Chieti, Italy

    Marcello Di Nisio

Authors
  1. Nick van Es
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  2. Suzanne M. Bleker
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  3. Ineke T. Wilts
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  4. Ettore Porreca
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  5. Marcello Di Nisio
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Corresponding author

Correspondence to Marcello Di Nisio.

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Funding

No external funds were used in the preparation of this manuscript.

Conflict of interest

Marcello Di Nisio has received consulting fees from Bayer Healthcare and fees for participation in the Advisory Board meetings for Grifols SPA, neither of which are related to this work. Nick van Es, Suzanne Bleker, Ineke Wilts, and Ettore Porreca have no conflicts of interest that might be relevant to the content of this review.

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van Es, N., Bleker, S.M., Wilts, I.T. et al. Prevention and Treatment of Venous Thromboembolism in Patients with Cancer: Focus on Drug Therapy. Drugs 76, 331–341 (2016). https://doi.org/10.1007/s40265-015-0526-3

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