Abstract

Cancer patients have increased risk of venous thromboembolism (VTE) as well as bleeding. For many years Low Molecule Heparin (LMHW) remained standard of care for treatment of cancer associated thrombosis (CAT). Recently Direct Oral Anticoagulants (DOACs) have shown similar efficacy and safety in large randomised control trials. Data from four recent trials done in cancer patients have highlighted importance of DOACs in these patients. DOACs are found simpler to administer with better compliance among these patients. However, there are several issues surrounding prescribing DOACs in cancer patients. Some of them are related to drug-to-drug interactions and others to increased risk of bleeding in mucosal cancers of gastrointestinal (GI) and urothelial tracts. In this review, author summarised and updated clinical information and compiled easy to use practical guide for treatment of VTE in cancer patients in flow-sheet manner. It is also suggested to establish a multidisciplinary cancer associated thrombosis clinic for these patients for long term follow-up.

Keywords: Venous Thromboembolism (VTE); Low Molecule Heparin (LMHW); Cancer Associated Thrombosis (CAT); Direct Oral Anticoagulants (DOACs); Gastrointestinal (GI); Deep Vein Thrombosis (DVT); Pulmonary Embolism (PE)

References

1. Chew HK., et al. “Incidence of venous thromboembolism and its effect on survival among patients with common cancers”. Archives of Internal Medicine 4 (2006): 458-464.
2. Khorana AA., et al. “Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy”. Journal of Thrombosis and Haemostasis 3 (2007): 632-634.
3. Horsted F., et al. “Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis”. PLOS Medicine 7 (2012): e1001275.
4. Nigel S Key., et al. “Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update”. Journal of Clinical Oncology 5 (2020): 496-520.
5. CAy J Beyer-Westendorf., et al. “Treatment of Cancer-Associated Venous Thromboembolism in the Age of Direct Oral Anticoagulants”. Annals of Oncology 6 (2019): 897-907.
6. Farge D., et al. “International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer”. The Lancet Oncology 10 (2016): e452-e466.
7. Mandala M and Labianca R. “European Society for Medical Oncology. Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management”. Thrombosis Research 2 (2010): S117-S119.
8. Kearon C., et al. “Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report”. Chest2 (2016): 315-352.
9. Watson HG., et al. “Guideline on aspects of cancer-related venous thrombosis”. British Journal of Haematology 5 (2015): 640-648.
10. Van der Hulle T., 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”. Journal of Thrombosis and Haemostasis 3 (2014): 320-328.
11. Wittkowsky AK. “Barriers to the long-term use of low-molecular weight heparins for treatment of cancer-associated thrombosis”. Journal of Thrombosis and Haemostasis 9 (2006): 2090-2091.
12. ASCO Clinical guidelines for Prevention and Treatment of VTE in Cancer Patients.
13. McBane R., et al. “Apixaban and Dalteparin in Active Malignancy Associated Venous Thromboembolism: The ADAM VTE Trial”. Journal of Thrombosis and Haemostasis (2019): 411-421.
14. Corinine Frere., et al. “Recent Advances in the Management of Cancer-Associated Thrombosis: New Hopes but New Challenges”. Cancers1 (2019): 71.
15. Ramya C Mosarla. “Anticoagulation Strategies in Patients with Cancer”. Journal of the American College of Cardiology 73 (2019): 1336-1349.
16. Giancarlo Agnelli., et al. “Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer”. The New England Journal of Medicine 382 (2020): 1599-1607.
17. Qamar A., et al. “Oral Anticoagulation in Patients With Liver Disease”. Journal of the American College of Cardiology 19 (2018): 2162-2175.
18. Jens Lutz., et al. “Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations”. International Journal of Nephrology and Renovascular Disease 10 (2017): 135-143.
19. David Erskine, DOAC dosing in renal impairment (2020).
20. Streiff MB., et al. “Venous thromboembolic disease”. Journal of the National Comprehensive Cancer Network 11 (2013): 1402-1429.
21. Lyman GH., et al. “Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update”. Journal of Clinical Oncology 31 (2013): 2189-2204.
22. Khorana AA., et al. “Evaluation of US prescription patterns: are treatment guidelines for cancer-associated venous thromboembolism being followed?” Thrombosis Research 145 (2016): 51-53.
23. Raskob GE., et al. “Edoxaban for the treatment of cancer-associated venous thromboembolism”. The New England Journal of Medicine (2017).
24. VanEs N., et al. “Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study”. Thrombosis and Haemostasis 114 (2015): 1268-1276.
25. Ay C., et al. “Antithrombotic therapy for prophylaxis and treatment of venous thromboembolism in patients with cancer: review of the literature on current practice and emerging options”. ESMO Open 2 (2017): e000188.
26. Komatsubara KM and Diuguid DL. “Clotting and bleeding in oncology patients: clinical scenarios and challenges”. Oncology 30 (2016): 936-940.
27. Gualandro DM., et al. “II Guidelines for perioperative evaluation of the Brazilian Society of Cardiology”. Arquivos Brasileiros de Cardiologia 3-1 (2011): 1-68.
28. ESMO Learning Module (2019).
29. Connolly SJ., et al. “ANNEXA‐4 Investigators. Full study report of Andexanet Alfa for bleeding associated with factor Xa inhibitors”. The New England Journal of Medicine 380 (2019): 1326‐1335.
30. Adam Cuker., et al. “Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum”. AJH6 (2019): 697-709.

Citation

Citation: Shahid Gilani. “Direct Oral Anticoagulants (DOACs) in Cancer Related Thromboembolism".Acta Scientific Cancer Biology 4.10 (2020): 07-15.

Copyright

Copyright: © 2020 Shahid Gilani. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.