Download PDF
Int J Angiol 2021; 30(04): 249-256
DOI: 10.1055/s-0041-1729920
Review Article

Cancer-Associated Atherothrombosis: The Challenge

Jochanan E. Naschitz
1   The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
2   Comprehensive Geriatric Ward, Bait Balev Nesher, Nesher, Israel
› Author Affiliations Funding There was no funding to this work.
› Further Information
    Permissions and Reprints

Abstract

The association between venous thrombosis and malignancy, having typical features of a paraneoplastic syndrome, has been established for a century. Currently, it is recognized that arterial thromboembolism (ATE) may also behave as a paraneoplastic syndrome. Recent matched cohort studies, systematic reviews, and observational studies concur in showing an increased incidence of acute coronary events, ischemic stroke, accelerated peripheral arterial disease, and in-stent thrombosis during the 6-month period before cancer diagnosis, peaking for 30 days immediately before cancer diagnosis. Cancer patients with ATE are at higher risk of in-hospital and long-term mortality as compared with noncancer patients. In the present review, we focus on the epidemiology, clinical variants and presentation, morbidity, mortality, primary and secondary prevention, and treatment of cancer-associated ATE. The awareness that cancer can be a risk factor for ATE and that cancer therapy can initiate cardiovascular complications make it mandatory to identify high-risk patients, modify preexistent cardiovascular risk factors, and adopt effective antithrombotic prophylaxis. For ATE prophylaxis, modifiable patient-related risk factors and oncology treatment–related factors are levers for intervention. Statins and platelet antiaggregants have been studied, but their efficacy for prevention of cancer-associated ATE remains to be demonstrated. Results of revascularization procedures for cancer-associated ATE are worse than for ATE in noncancer patients. It is important that a multidisciplinary approach is adopted for making informed decisions, by involving the vascular surgeon, interventional radiologist, oncologist, and palliative medicine, as well as the patients and their family.

Keywords

cancer - peripheral arterial disease - coronary artery disease - stroke - paraneoplastic - thrombosis


Publication History

Article published online:
19 July 2021

© 2021. International College of Angiology. This article is published by Thieme.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Trousseau A. Phlegmasia alba dolens. In: Clinique Medicale de l'Hotel-Dieu de Paris. 2nd ed.. Vol. 3. Paris: J.-B. Baillière et fils; 1865: 695-727
    Search in Google Scholar
  • 2 Sack Jr GH, Levin J, Bell WR. Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine (Baltimore) 1977; 56 (01) 1-37
    CrossrefPubMedSearch in Google Scholar
  • 3 Navi BB, Reiner AS, Kamel H. et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol 2017; 70 (08) 926-938
    CrossrefPubMedSearch in Google Scholar
  • 4 Sundbøll J, Veres K, Horváth-Puhó E, Adelborg K, Sørensen HT. Risk and prognosis of cancer after lower limb arterial thrombosis. Circulation 2018; 138 (07) 669-677
    CrossrefPubMedSearch in Google Scholar
  • 5 Brenner B, Bikdeli B, Tzoran I. et al; RIETE Investigators. Arterial ischemic events are a major complication in cancer patients with venous thromboembolism. Am J Med 2018; 131 (09) 1095-1103
    CrossrefPubMedSearch in Google Scholar
  • 6 Grilz E, Königsbrügge O, Posch F. et al. Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer. Haematologica 2018; 103 (09) 1549-1556
    CrossrefPubMedSearch in Google Scholar
  • 7 Naschitz JE, Kovaleva J, Shaviv N, Rennert G, Yeshurun D. Vascular disorders preceding diagnosis of cancer: distinguishing the causal relationship based on Bradford-Hill guidelines. Angiology 2003; 54 (01) 11-17
    CrossrefPubMedSearch in Google Scholar
  • 8 Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 1. J Am Coll Cardiol 2017; 70 (20) 2536-2551
    CrossrefPubMedSearch in Google Scholar
  • 9 Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ETH. Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 2. J Am Coll Cardiol 2017; 70 (20) 2552-2565
    CrossrefPubMedSearch in Google Scholar
  • 10 Naschitz JE, Yeshurun D, Abrahamson J. Arterial occlusive disease in occult cancer. Am Heart J 1992; 124 (03) 738-745
    CrossrefPubMedSearch in Google Scholar
  • 11 Naschitz JE, Schechter L, Chang JB. Intermittent claudication associated with cancer--case studies. Angiology 1987; 38 (09) 696-704
    CrossrefPubMedSearch in Google Scholar
  • 12 Naschitz JE, Yeshurun D, Abrahamson J. et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992; 69 (11) 2712-2720
    CrossrefPubMedSearch in Google Scholar
  • 13 Navi BB, Reiner AS, Kamel H. et al. Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Blood 2019; 133 (08) 781-789
    CrossrefPubMedSearch in Google Scholar
  • 14 Abbott JD, Ahmed HN, Vlachos HA, Selzer F, Williams DO. Comparison of outcome in patients with ST-elevation versus non-ST-elevation acute myocardial infarction treated with percutaneous coronary intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry). Am J Cardiol 2007; 100 (02) 190-195
    CrossrefPubMedSearch in Google Scholar
  • 15 Wang F, Gulati R, Lennon RJ. et al. Cancer history portends worse acute and long-term noncardiac (but not cardiac) mortality after primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction. Mayo Clin Proc 2016; 91 (12) 1680-1692
    CrossrefPubMedSearch in Google Scholar
  • 16 Zöller B, Ji J, Sundquist J, Sundquist K. Risk of coronary heart disease in patients with cancer: a nationwide follow-up study from Sweden. Eur J Cancer 2012; 48 (01) 121-128
    CrossrefPubMedSearch in Google Scholar
  • 17 Kaschwich M, Peters F, Hischke S. et al. Long-term incidence of cancer after index treatment for symptomatic peripheral arterial disease - a health insurance claims data analysis. Vasa 2020; 49 (06) 493-499
    CrossrefPubMedSearch in Google Scholar
  • 18 Navi BB, Singer S, Merkler AE. et al. Recurrent thromboembolic events after ischemic stroke in patients with cancer. Neurology 2014; 83 (01) 26-33
    CrossrefPubMedSearch in Google Scholar
  • 19 Lee JM, Yoon C-H. Acute coronary stent thrombosis in cancer patients: a case series report. Korean Circ J 2012; 42 (07) 487-491
    CrossrefPubMedSearch in Google Scholar
  • 20 Ganatra S, Sharma A, Levy MS. Re-evaluating the safety of drug-eluting stents in cancer patients. JACC Cardiovasc Interv 2017; 10 (22) 2334-2337
    CrossrefPubMedSearch in Google Scholar
  • 21 Yu J, Li A, Laureano M, Crowther M. Frequency of arterial thromboembolism in populations with malignancies: a systematic review. Thromb Res 2019; 184: 16-23
    CrossrefPubMedSearch in Google Scholar
  • 22 Prandoni P. Venous and arterial thrombosis: is there a link?. Adv Exp Med Biol 2017; 906: 273-283
    CrossrefPubMedSearch in Google Scholar
  • 23 Tzoran I, Rebibo-Sabbah A, Brenner B, Aharon A. Disease dynamics in patients with acute myeloid leukemia: new biomarkers. Exp Hematol 2015; 43 (11) 936-943
    CrossrefPubMedSearch in Google Scholar
  • 24 Faille D, Frere C, Cuisset T. et al. CD11b+ leukocyte microparticles are associated with high-risk angiographic lesions and recurrent cardiovascular events in acute coronary syndromes. J Thromb Haemost 2011; 9 (09) 1870-1873
    CrossrefPubMedSearch in Google Scholar
  • 25 Nadir Y, Sarig G, Axelman E. et al. Heparanase procoagulant activity is elevated and predicts survival in non-small cell lung cancer patients. Thromb Res 2014; 134 (03) 639-642
    CrossrefPubMedSearch in Google Scholar
  • 26 Bick RL. Cancer-associated thrombosis. N Engl J Med 2003; 349 (02) 109-111
    CrossrefPubMedSearch in Google Scholar
  • 27 Falanga A, Schieppati F, Russo L. Pathophysiology 1. Mechanisms of thrombosis in cancer patients. Cancer Treat Res 2019; 179: 11-36
    CrossrefPubMedSearch in Google Scholar
  • 28 Mitrugno A, Tormoen GW, Kuhn P, McCarty OJT. The prothrombotic activity of cancer cells in the circulation. Blood Rev 2016; 30 (01) 11-19
    CrossrefPubMedSearch in Google Scholar
  • 29 Tapia-Vieyra JV, Delgado-Coello B, Mas-Oliva J. Atherosclerosis and cancer; a resemblance with far-reaching implications. Arch Med Res 2017; 48 (01) 12-26
    CrossrefPubMedSearch in Google Scholar
  • 30 Raposeiras Roubín S, Cordero A. The two-way relationship between cancer and atherosclerosis. Rev Esp Cardiol (Engl Ed) 2019; 72 (06) 487-494
    CrossrefPubMedSearch in Google Scholar
  • 31 Seizer P, May AE. Platelets and matrix metalloproteinases. Thromb Haemost 2013; 110 (05) 903-909
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Heinmöller E, Weinel RJ, Heidtmann HH. et al. Studies on tumor-cell-induced platelet aggregation in human lung cancer cell lines. J Cancer Res Clin Oncol 1996; 122 (12) 735-744
    CrossrefPubMedSearch in Google Scholar
  • 33 Herrmann J, Lerman A. The endothelium - the cardiovascular health barometer. Herz 2008; 33 (05) 343-353
    CrossrefPubMedSearch in Google Scholar
  • 34 Aronson D, Brenner B. Arterial thrombosis and cancer. Thromb Res 2018; 164 (Suppl. 01) S23-S28
    CrossrefPubMedSearch in Google Scholar
  • 35 Han X-J, Li J-Q, Khannanova Z, Li Y. Optimal management of coronary artery disease in cancer patients. Chronic Dis Transl Med 2020; 5 (04) 221-233
    PubMedSearch in Google Scholar
  • 36 Tuzovic M, Herrmann J, Iliescu C, Marmagkiolis K, Ziaeian B, Yang EH. Arterial thrombosis in patients with cancer. Curr Treat Options Cardiovasc Med 2018; 20 (05) 40
    CrossrefPubMedSearch in Google Scholar
  • 37 Khemasuwan D, Divietro ML, Tangdhanakanond K, Pomerantz SCEG, Eiger G. Statins decrease the occurrence of venous thromboembolism in patients with cancer. Am J Med 2010; 123 (01) 60-65
    CrossrefPubMedSearch in Google Scholar
  • 38 Shai A, Rennert HS, Lavie O. et al. Statins, aspirin and risk of venous thromboembolic events in breast cancer patients. J Thromb Thrombolysis 2014; 38 (01) 32-38
    CrossrefPubMedSearch in Google Scholar
  • 39 Detrano R, Guerci AD, Carr JJ. et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008; 358 (13) 1336-1345
    CrossrefPubMedSearch in Google Scholar
  • 40 Sudhakar R. Response to treatment and outcomes of acute coronary syndrome in the cancer population. Clin Cardiol 2012; 35 (10) 646
    CrossrefPubMedSearch in Google Scholar
  • 41 Moran TB, Plana JC. Management of patients with acute coronary syndrome and cancer. Curr Cardiol Rep 2020; 22 (12) 159
    CrossrefPubMedSearch in Google Scholar
  • 42 Gomes M, Khorana AA. Risk assessment for thrombosis in cancer. Semin Thromb Hemost 2014; 40 (03) 319-324
    Thieme ConnectPubMedSearch in Google Scholar
  • 43 Effron MB, Gibson CM. Dual (anticoagulant plus single antiplatelet) vs triple (anticoagulant plus dual antiplatelet) antithrombotic therapy - “real world” experience. Prog Cardiovasc Dis 2018; 60 (4–5): 531-536
    CrossrefPubMedSearch in Google Scholar
  • 44 Iliescu CA, Grines CL, Herrmann J. et al. SCAI expert consensus statement: evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (endorsed by the Cardiological Society of India, and Sociedad Latino Americana de Cardiologıa Intervencionista). Catheter Cardiovasc Interv 2016; 87 (05) E202-E223
    CrossrefPubMedSearch in Google Scholar
  • 45 McCarthy CP, Steg G, Bhatt DL. The management of antiplatelet therapy in acute coronary syndrome patients with thrombocytopenia: a clinical conundrum. Eur Heart J 2017; 38 (47) 3488-3492
    CrossrefPubMedSearch in Google Scholar
  • 46 Urban P, Mehran R, Colleran R. et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J 2019; 40 (31) 2632-2653
    CrossrefPubMedSearch in Google Scholar
  • 47 Javid M, Magee TR, Galland RB. Arterial thrombosis associated with malignant disease. Eur J Vasc Endovasc Surg 2008; 35 (01) 84-87
    CrossrefPubMedSearch in Google Scholar
  • 48 Villemur B, Payraud E, Seetha V. et al. Arterial bypass iterative thrombosis and cancer: three cases [in French]. J Mal Vasc 2014; 39 (01) 14-17
    CrossrefPubMedSearch in Google Scholar
  • 49 Balanescu DV, Donisan T, Deswal A. et al. Acute myocardial infarction in a high-risk cancer population: outcomes following conservative versus invasive management. Int J Cardiol 2020; 313: 1-8
    CrossrefPubMedSearch in Google Scholar
  • 50 Elbadawi A, Elgendy IY, Ha LD. et al. National trends and outcomes of percutaneous coronary intervention in patients ≥70 years of age with acute coronary syndrome (from the National Inpatient Sample Database). Am J Cardiol 2019; 123 (01) 25-32
    CrossrefPubMedSearch in Google Scholar
  • 51 Bharadwaj AS, Swamy PM, Mamas MA. Outcomes of percutaneous coronary interventions in cancer patients. Expert Rev Cardiovasc Ther 2020; 18 (01) 25-32
    CrossrefPubMedSearch in Google Scholar
  • 52 Iannaccone M, D'Ascenzo F, Vadalà P. et al. Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy. Eur Heart J Acute Cardiovasc Care 2018; 7 (07) 631-638
    CrossrefPubMedSearch in Google Scholar
  • 53 Quintana RA, Monlezun DJ, Davogustto G. et al. Outcomes following percutaneous coronary intervention in patients with cancer. Int J Cardiol 2020; 300: 106-112
    CrossrefPubMedSearch in Google Scholar
  • 54 Piróth Z. PCI in patients with cancer: what is the evidence?. Int J Cardiol 2020; 304: 150-151
    CrossrefPubMedSearch in Google Scholar
  • 55 Canale ML, Bisceglia I, Lestuzzi C, Parrini I. ANMCO Cardio-Oncology Task Force. Arterial thrombosis in cancer: spotlight on the neglected vessels. Anticancer Res 2019; 39 (09) 4619-4625
    CrossrefPubMedSearch in Google Scholar
  • 56 Milazzo V, Cosentino N, Campodonico J. et al. Characteristics, management, and outcomes of acute coronary syndrome patients with cancer. J Clin Med 2020; 9 (11) 3642
    CrossrefPubMedSearch in Google Scholar