Thromboembolism and Bleeding
While thromboembolism and bleeding appear, at first glance, to be hematological processes at opposite ends of the clinical spectrum, they share many commonalities of relevance to palliative care teams. Both are increased in the malignant state, particularly with metastatic disease, and consequently confer a significant symptom burden, resulting in high level of distress for patients and carers. Furthermore, they are often the cause, or contributory cause, of death and frequently complicate care at the end of life.
The evidence base for the management of cancer-associated thrombosis (CAT) has increased significantly over the past 15 years, yet few studies have included or considered patients with advanced cancer or those nearing the end of life. With respect to the management of bleeding at the end of life, particularly terminal hemorrhage, management is informed by little more than case reports and expert opinion.
This chapter will comprise of two sections. First, it will provide an overview of the management of bleeding in the palliative setting with particular focus on terminal hemorrhage. The second section will focus on the treatment and prevention of venous thromboembolism in the advanced cancer setting, including the management of patients with recurrent thrombosis, thrombocytopenia, and bleeding. It will also review the new oral anticoagulants and consider their place in CAT management.
- A Medical Research Council (MRC) randomised trial of palliative radiotherapy with two fractions or a single fraction in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Medical Research Council Lung Cancer Working Party. Br J Cancer. 1992;65(6):934–41.CrossRefGoogle Scholar
- Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AY, Subcommittee on Haemostasis, et al. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal. J Thromb Haemost: JTH. 2014;12(1):116–7.PubMedCrossRefGoogle Scholar
- Eleje GU, Eke AC, Igberase GO, Igwegbe AO, Eleje LI. Palliative interventions for controlling vaginal bleeding in advanced cervical cancer. Cochrane Database Syst Rev. 2015;(5):CD011000.Google Scholar
- Harrington DJ, Western H, Seton-Jones C, Rangarajan S, Beynon T, Shearer MJ. A study of the prevalence of vitamin K deficiency in patients with cancer referred to a hospital palliative care team and its association with abnormal haemostasis. J Clin Pathol. 2008;61(4): 537–40.PubMedCrossRefGoogle Scholar
- Martins BC, Wodak S, Gusmon CC, Safatle-Ribeiro AV, Kawaguti FS, Baba ER, et al. Argon plasma coagulation for the endoscopic treatment of gastrointestinal tumor bleeding: a retrospective comparison with a non-treated historical cohort. United European Gastroenterol J. 2016;4(1):49–54.PubMedCrossRefGoogle Scholar
- 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(15):1729–35.PubMedCrossRefGoogle Scholar
- National Institute for Health and Care Excellence (NICE). Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. NICE Guideline (NG89). NICE publishing, London; 2018.Google Scholar
- Preston NJ, Hurlow A, Brine J, Bennett MI. Blood transfusions for anaemia in patients with advanced cancer. Cochrane Database Syst Rev. 2012;(2):CD009007.Google Scholar
- Prins MLA, Brighton T, Lyons R, Rehm J, Trajanovic M, Davidson B, Beyer-Westendorf J, Pap A, Berkowitz S, Cohen A, Kovacs M, Wells P, Prandoni P. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014;1(1):e37–e46A.PubMedCrossRefGoogle Scholar
- Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378(7):615–24.PubMedCrossRefGoogle Scholar
- Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013;17(10):1–79.PubMedPubMedCentralCrossRefGoogle Scholar
- Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18): 2276–315.PubMedCrossRefGoogle Scholar
- Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018.Google Scholar