Skip to main content
SpringerLink
Log in

Thromboembolism and Bleeding

  • Living reference work entry
  • First Online:
Textbook of Palliative Care

  • 283 Accesses

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • 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.

    Article  Google Scholar 

  • Abt D, Bywater M, Engeler DS, Schmid HP. Therapeutic options for intractable hematuria in advanced bladder cancer. Int J Urol. 2013;20(7):651–60.

    Article  Google Scholar 

  • Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.

    Article  CAS  Google Scholar 

  • Ambrus JL, Ambrus CM, Mink IB, Pickren JW. Causes of death in cancer patients. J Med. 1975;6(1):61–4.

    CAS  PubMed  Google Scholar 

  • Bennett P, Patterson K, Noble S. Predicting post-traumatic stress and health anxiety following a venous thrombotic embolism. J Health Psychol. 2016;21(5):863–71.

    Article  Google Scholar 

  • Broadley KE, Kurowska A, Dick R, Platts A, Tookman A. The role of embolization in palliative care. Palliat Med. 1995;9(4):331–5.

    Article  CAS  Google Scholar 

  • Cameron MG, Kersten C, Vistad I, Fossa S, Guren MG. Palliative pelvic radiotherapy of symptomatic incurable rectal cancer – a systematic review. Acta Oncol. 2014;53(2):164–73.

    Article  Google 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.

    Article  CAS  Google Scholar 

  • Carrier M, Lazo-Langner A, Shivakumar S, Tagalakis V, Zarychanski R, Solymoss S, et al. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med. 2015;373(8):697–704.

    Article  CAS  Google Scholar 

  • Chee CE, Ashrani AA, Marks RS, Petterson TM, Bailey KR, Melton LJ 3rd, et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood. 2014;123(25):3972–8.

    Article  CAS  Google Scholar 

  • Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98(4):756–64.

    CAS  PubMed  Google Scholar 

  • Dequanter D, Shahla M, Paulus P, Aubert C, Lothaire P.Transarterial endovascular treatment in the management of life-threatening carotid blowout syndrome in head and neck cancer patients: review of the literature. J Mal Vasc. 2013;38(6):341–4.

    Article  CAS  Google Scholar 

  • EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–510.

    Article  Google 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 

  • Eriksson LG, Ljungdahl M, Sundbom M, Nyman R. Transcatheter arterial embolization versus surgery in the treatment of upper gastrointestinal bleeding after therapeutic endoscopy failure. J Vasc Interv Radiol. 2008;19(10):1413–8.

    Article  Google Scholar 

  • Gando S. The utility of a diagnostic scoring system for disseminated intravascular coagulation. Crit Care Clin. 2012;28(3):373–88, vi

    Article  Google Scholar 

  • Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med. 2012;366(9):864–6.

    Article  CAS  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.

    Article  CAS  Google Scholar 

  • Harris DG, Finlay IG, Flowers S, Noble SI. The use of crisis medication in the management of terminal haemorrhage due to incurable cancer: a qualitative study. Palliat Med. 2011;25(7):691–700.

    Article  CAS  Google Scholar 

  • Havig O. Deep vein thrombosis and pulmonary embolism. An autopsy study with multiple regression analysis of possible risk factors. Acta Chir Scand Suppl. 1977;478:1–120.

    CAS  PubMed  Google Scholar 

  • Hokusai VTEI, Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406–15.

    Article  Google Scholar 

  • 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(12):1062–72.

    Article  CAS  Google Scholar 

  • Hunt BJ. The current place of tranexamic acid in the management of bleeding. Anaesthesia. 2015;70(Suppl 1):50–3, e18

    Article  CAS  Google Scholar 

  • Johnson MJ, Sherry K. How do palliative physicians manage venous thromboembolism? Palliat Med. 1997;11(6):462–8.

    Article  CAS  Google Scholar 

  • Johnson MJ, Sproule MW, Paul J. The prevalence and associated variables of deep venous thrombosis in patients with advanced cancer. Clin Oncol (R Coll Radiol). 1999;11(2):105–10.

    Article  CAS  Google Scholar 

  • Johnson MJ, Sheard L, Maraveyas A, Noble S, Prout H, Watt I, et al. Diagnosis and management of people with venous thromboembolism and advanced cancer: how do doctors decide? A qualitative study. BMC Med Inform Decis Mak. 2012;12:75.

    Article  Google Scholar 

  • Johnson MJ, McMillan B, Fairhurst C, Gabe R, Ward J, Wiseman J, et al. Primary thromboprophylaxis in hospices: the association between risk of venous thromboembolism and development of symptoms. J Pain Symptom Manag. 2014;48(1):56–64.

    Article  Google Scholar 

  • Kakkar VV, Howe CT, Flanc C, Clarke MB. Natural history of postoperative deep-vein thrombosis. Lancet. 1969;2(7614):230–2.

    Article  CAS  Google Scholar 

  • Kawaguchi T, Tanaka M, Itano S, Ono N, Shimauchi Y, Nagamatsu H, et al. Successful treatment for bronchial bleeding from invasive pulmonary metastasis of hepatocellular carcinoma: a case report. Hepato-Gastroenterology. 2001;48(39):851–3.

    CAS  PubMed  Google Scholar 

  • 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: JTH. 2007a;5(3):632–4.

    Article  CAS  Google Scholar 

  • Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 2007b;110(10):2339–46.

    Article  Google Scholar 

  • Kundu A, Sardar P, Chatterjee S, Aronow WS, Owan T, Ryan JJ. Minimizing the risk of bleeding with NOACs in the elderly. Drugs Aging. 2016;33:491–500.

    Article  CAS  Google Scholar 

  • Langendijk JA, ten Velde GP, Aaronson NK, de Jong JM, Muller MJ, Wouters EF. Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys. 2000;47(1): 149–55.

    Article  CAS  Google Scholar 

  • Lee AY, Peterson EA. Treatment of cancer-associated thrombosis. Blood. 2013;122(14):2310–7.

    Article  CAS  Google Scholar 

  • 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(2):146–53.

    Article  CAS  Google Scholar 

  • Lee AY, 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: a randomized clinical trial. JAMA. 2015;314(7):677–86.

    Article  CAS  Google Scholar 

  • Louzada ML, Carrier M, Lazo-Langner A, Dao V, Kovacs MJ, Ramsay TO, et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation. 2012;126(4): 448–54.

    Article  Google 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.

    Article  CAS  Google Scholar 

  • Meignan M, Rosso J, Gauthier H, Brunengo F, Claudel S, Sagnard L, et al. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med. 2000;160(2):159–64.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

  • Nabi G, Sheikh N, Greene D, Marsh R. Therapeutic transcatheter arterial embolization in the management of intractable haemorrhage from pelvic urological malignancies: preliminary experience and long-term follow-up. BJU Int. 2003;92(3):245–7.

    Article  CAS  Google 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 

  • Noble SF, Finlay IG. Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study. Palliat Med. 2005;19(3):197–201.

    Article  Google Scholar 

  • Noble SI, Finlay IG. Have palliative care teams’ attitudes toward venous thromboembolism changed? A survey of thromboprophylaxis practice across British specialist palliative care units in the years 2000 and 2005. J Pain Symptom Manag. 2006;32(1):38–43.

    Article  Google Scholar 

  • Noble S, Johnson M. Finding the evidence for thromboprophylaxis in palliative care: first let us agree on the question. Palliat Med. 2010;24(4):359–61.

    Article  Google Scholar 

  • Noble SI, Nelson A, Turner C, Finlay IG. Acceptability of low molecular weight heparin thromboprophylaxis for inpatients receiving palliative care: qualitative study. BMJ. 2006;332(7541):577–80.

    Article  CAS  Google Scholar 

  • Noble SI, Nelson A, Finlay IG. Factors influencing hospice thromboprophylaxis policy: a qualitative study. Palliat Med. 2008;22(7):808–13.

    Article  CAS  Google Scholar 

  • Noble S, Lewis R, Whithers J, Lewis S, Bennett P. Long-term psychological consequences of symptomatic pulmonary embolism: a qualitative study. BMJ Open. 2014;4(4):e004561.

    Article  Google Scholar 

  • Noble S, Matzdorff A, Maraveyas A, Holm MV, Pisa G. Assessing patients’ anticoagulation preferences for the treatment of cancer-associated thrombosis using conjoint methodology. Haematologica. 2015a;100(11): 1486–92.

    Article  CAS  Google Scholar 

  • Noble S, Prout H, Nelson A. Patients’ Experiences of LIving with CANcer-associated thrombosis: the PELICAN study. Patient Prefer Adherence. 2015b;9: 337–45.

    Article  Google Scholar 

  • Noble S, Pease N, Sui J, Davies J, Lewis S, Malik U, et al. Impact of a dedicated cancer-associated thrombosis service on clinical outcomes: a mixed-methods evaluation of a clinical improvement exercise. BMJ Open. 2016;6(11):e013321.

    Article  Google Scholar 

  • O’Shaughnessy DF, Atterbury C, Bolton Maggs P, Murphy M, Thomas D, Yates S, et al. Guidelines for the use of fresh-frozen plasma cryoprecipitate and cryosupernatant. Br J Haematol. 2004;126(1):11–28.

    Article  Google Scholar 

  • Pace V, Hall E, Bailey C. Prophylactic heparin in palliative care: a cautious welcome. BMJ. 2006;332(7543): 728–9.

    Article  Google Scholar 

  • Pereira J, Phan T. Management of bleeding in patients with advanced cancer. Oncologist. 2004;9(5):561–70.

    Article  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.

    Article  Google 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.

    Article  CAS  Google Scholar 

  • Rickles FR, Falanga A. Activation of clotting factors in cancer. Cancer Treat Res. 2009;148:31–41.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

  • Rodrigues G, Videtic GM, Sur R, Bezjak A, Bradley J, Hahn CA, et al. Palliative thoracic radiotherapy in lung cancer: an American Society for Radiation Oncology evidence-based clinical practice guideline. Pract Radiat Oncol. 2011;1(2):60–71.

    Article  Google Scholar 

  • Sakr L, Dutau H. Massive hemoptysis: an update on the role of bronchoscopy in diagnosis and management. Respiration. 2010;80(1):38–58.

    Article  CAS  Google Scholar 

  • Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS, Goldsmith M, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19(5):1519–38.

    Article  CAS  Google Scholar 

  • Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–52.

    Article  CAS  Google Scholar 

  • Seaman S, Nelson A, Noble S. Cancer-associated thrombosis, low-molecular-weight heparin, and the patient experience: a qualitative study. Patient Prefer Adherence. 2014;8:453–61.

    PubMed  PubMed Central  Google Scholar 

  • Sheard L, Prout H, Dowding D, Noble S, Watt I, Maraveyas A, et al. Barriers to the diagnosis and treatment of venous thromboembolism in advanced cancer patients: a qualitative study. Palliat Med. 2013;27(4): 339–48.

    Article  Google Scholar 

  • Tardy B, Picard S, Guirimand F, Chapelle C, Danel Delerue M, Celarier T, et al. Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study. J Thromb Haemost: JTH. 2017;15(3): 420–8.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

  • van der Hulle T, den Exter PL, Kooiman J, van der Hoeven JJ, Huisman MV, Klok FA. Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. J Thromb Haemost: JTH. 2014;12(7): 1116–20.

    Article  Google Scholar 

  • Wells PS, Forgie MA, Rodger MA. Treatment of venous thromboembolism. JAMA. 2014;311(7):717–28.

    Article  CAS  Google 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 

Download references

Author information

Authors and Affiliations

  1. Marie Curie Palliative Care Research Centre, Division of Population Medicine, Cardiff University, Cardiff, UK

    Simon Noble

Authors
  1. Simon Noble
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon Noble .

Editor information

Editors and Affiliations

  1. HammondCare Learning and Research Centre, Greenwich Hospital, Greenwich, NSW, Australia

    Roderick Duncan MacLeod

  2. Vrije Universiteit Brussel, VUB-UGent End-of-Life Care Research Grou Vrije Universiteit Brussel, Brussels, Belgium

    Lieve Van den Block

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Noble, S. (2018). Thromboembolism and Bleeding. In: MacLeod, R., Van den Block, L. (eds) Textbook of Palliative Care. Springer, Cham. https://doi.org/10.1007/978-3-319-31738-0_71-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-31738-0_71-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-31738-0

  • Online ISBN: 978-3-319-31738-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation