Preventing Thrombosis in Cancer Patients

Budi Setiawan, Eko Adhi Pangarsa, Damai Santosa, Ridho M Naibaho, Rahajuningsih Dharma Setiabudy, Catharina Suharti


Thromboembolism events, either venous (VTE) or arterial thromboembolism (ATE) remain a highly prevalent complication in cancer patients. Thrombosis is a leading cause of death, contributor to significant morbidity, the reason of delayed cancer treatment, leading to increased cancer financing and expenses. Both cancer and its treatment are recently found to be related to vascular inflammation through the induction of tissue factor (TF) expression and promoting a procoagulant state which triggers the activation of coagulation system. Several risk factors may also coexist such as dehydration, immobilization, smoking, obesity, previous DVT, etc. Even in patients with asymptomatic deep vein thrombosis (DVT), they have a three-fold increase in mortality. The high morbidity and mortality of VTE raises the need for thromboprophylaxis to reduce the incidence of overt thrombosis, albeit against its possible side effects related to anticoagulant prescription. This article highlighted the clinical perspectives for thromboprophylaxis while counting on the risk stratification in a particular cancer patient.


thrombosis; cancer; inflammation; thromboprophylaxis


Editorial. Advancing cancer therapy. Nature Cancer. 2021;2:245-6.

Blom JW, Doggen CJM. Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293:715-22.

American Cancer Society. Global cancer facts & figures. 4 th edition. International Agency for research on Cancer. The World Health Organization; 2018.

Gervaso L, Dave H, Khorana AA. Venous and arterial thromboembolism in patients with cancer. J Am College Cardiol. 2021;3:173-90.

National Institute for Health and Care Excellence. Venous thromboembolism in adults: diagnosis and management, 2013. Last updated: 25 January 2021.

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

Prandoni P, Lensing AWA, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100:3484-8.

Suharti C. Tromboemboli vena pada kanker (article in Bahasa Indonesia). Medica Hospitalia. 2013;1:143-9.

Al-Samkari H, Connors JM. Managing the competing risks of thrombosis, bleeding, and anticoagulation in patients with malignancy. Blood Adv. 2019;3:71-9.

Mulder FI, Bosch FTM, van Es N. Primary thromboprophylaxis in ambulatory cancer patients : where do we stand ? Cancers. 2020;12:1-17.

Elting LS, Escalante CP, Cooksley C, et al. Outcomes and cost of deep venous thrombosis among patients with Cancer. JAMA. 2004;164:1653-61.

Indonesian Society of Thrombosis and Hemostasis. The national guideline on venous thormboembolism (in Bahasa Indonesia). 2018.

Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9(7):e1001275.

Cohen AT, Katholing A, Rietbrock S, Bamber L, Martinez C. Epidemiology of first and recurrent venous thromboembolism in patients with active cancer A population-based cohort study. Thromb Haemost. 2017;117:57-65.

Iorga RA, Bratu OG, Marcu RD, et al. Venous thromboembolism in cancer patients: still looking for answers. Exp Ther Med. 2019;18:5026-32.

Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood. 2013;122:1712-24.

Angchaisuksiri P. Cancer-associated thrombosis in Asia. Thromb J. 2016;14(Suppl. 1):26.

Sutandyo N, Tobing DL, Kardinah. Risk Factors of Deep Vein Thrombosis in Cancer Patients. Iran J Blood & Cancer. 2018;10:117-23.

Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thormboprophylaxis. Cancer. 2011;117:1334-9.

Streiff MB. Association between cancer types, cancer treatments, and venous thromboembolism in medical oncology patients. Clin Adv Hematol Oncol. 2013;11:349-57.

Chew HK, Wun T, Harvey D, et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166:458-64.

Eichinger S. Cancer associated thrombosis: risk factors and outcomes. Thromb Res. 2016;140:S12-S17.

Sproul EE. Carcinoma and venous thormbosis: the frequency of association of carcinoma in the body or tail of the pancreas with multiple venous thormbosis. Cancer Res. 1998;34:566-85.

Karin M. NF- kB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 2009:1: a000141.

Boccaccio C, Paolo M. Comoglio. Oncogenesis, cancer and hemostasis. In: Khorana AA, Francis CW, eds. Cancer-associated thrombosis. New York, USA: Informa Healthcare Inc.; 2008. p. 1-15.

Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9:7204-18.

Park MH, Hong JT. Roles of NF- κB in cancer and inflammatory diseases and their therapeutic approaches. Cells. 2016;5:15.

Setiawan B, Rosalina R, Pangarsa EA, Santosa D, Suharti C. Clinical evaluation for the role of high-sensitivity C-reactive protein in combination with D-dimer and Wells score probability test to predict the incidence of deep vein thrombosis among cancer patients. Int J Gen Med. 2020;13: 587-594.

Kirwan CC, McCollum CN, McDowell G, Byrne GJ. Investigation of proposed mechanisms of chemotherapy-induced venous thromboembolism: endothelial cell activation and procoagulant release due to apoptosis. Clin Appl Thromb. 2015;2:420-7.

Sahebkar A, Serban C, Ursoniu S, et al., for Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials. Thromb Haemost. 2016;115:520-32.

Setiawan B, Permatadewi CO, de Samakto B, et al. Von Willebrand factor: antigen and ADAMTS-13 level, but not soluble P-selectin , are risk factors for the first asymptomatic deep vein thrombosis in cancer patients undergoing chemotherapy. Thromb J. 2020;18:33.

Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-8.

Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy : the Protecht score. Intern Emerg Med. 2012:7:291-2.

Pelzer U, Sinn M, Stieler J, Riess H. Primäre medikamentöse thromboembolieprophylaxe bei ambulanten Patienten mit fortgeschrittenem pankreaskarzinom unter chemotherapie ? Dtsch Med Wochenschr. 2013;138:2084-8.

Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-82.

Connolly GC, Francis CW. Cancer-associated thrombosis. Hematology Am Soc Hematol Educ Program. 2013;2013:684-91.

Gerotziafas GT, Taher A, Abdel-Razeq H, et al. A predictive score for thrombosis associated with breast, colorectal, lung, or ovarian Cancer: The Prospective COMPASS – Cancer-Associated Thrombosis Study. Oncologist. 2017;22:1222-31.

Cella CA, Di Minno G, Carlomagno C, et al. Preventing venous thromboembolism in ambulatory cancer patients: The ONKOTEV Study. Oncologist. 2017:22601-8.

Chi G, Goldhaber SZ, Kittelson JM, et al. Effect of extended-duration thromboprophylaxis on veous thromboembolism and major bleeding among acutely ill hospitlaized medical patients: a bivariate analysis. J Thromb Haemost. 2017;15:1913-22.

Al-Shamkari H, Connors JM. Managing the competing risks of thrombosis, bleeding, and anticoagulation in patients with malignancy. Blood Adv. 2019;3:3770-9.

Skeik N, Westergard E. Reccomendations for VTE prophylaxis in medically ill patients. Ann Vasc Dis. 2020;13:38-44.

Key NS, Chb MB, Khorana AA, Kuderer NM, Bohlke K, Lee AYY. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. 2019.

Farge D, Frere C, Connors JM, et al. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2019;20:e566-81.

Khorana AA. The NCCN clinical practice guidelines on venous thromboembolic disease: strategies for improveing VTE prophylaxis in hospitalized cancer patients. Oncologist. 2007;12:1361-70. doi:10.1634/theoncologist.12-11-1361.

Alikhan R, Cohen AT, Combe S, et al. Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul Fibronolysis. 2003;l(14):341-6.

Leizorovicz A, Cohen AT, Turpie AGG, Olsson C, Vaitkus PT, Goldhaber SZ and for the PREVENT Medical Thromboprophylaxis Study Group. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thmoboembolism in acutely ill medical patients. Circulation. 2004;110:874-9.

Cohen AT, Davidson BL, Gallus AS, et al. ARTEMIS Investigators. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ. 2006;332:325-9.

Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019;380:720-8.

Parker A, Peterson E, Lee AYY, et al. Risk stratification for the development of venous thromboembolism in hospitalized patients with cancer. J Thromb Haemost. 2018;16:1321-6.

Mulder FI, Candeloro M, Kamphuisen PW, et al., CAT-prediction collaborators. The Khorana score for prediction of venous a systematic review and meta-analysis. Haematologica. 2019;104:1277-87.

Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315-52.

Streiff MB, Holmstrom B, Angelini D, et al. NCCN Guidelines® Insights: Cancer-associated venous thromboembolic disease, Version 2.2018. Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2018;16:1289-303.

Atmakusuma TD, Tambunan KL, Sukrisman L, et al. Underutilization of anticoagulant for venous thromboembolism prophylaxis in three hospitals in Jakarta. Acta Medica Indones. 2015;47:136-45.

Mahe I, Chidiac J, Helfer H, Noble S. Factors influencing adherence to clinical guidelines in the management of cancer-associated thrombosis. J Thromb Haemost. 2016;14:2107-13.

Bradley T, Brasel KJ, Miller JJ, Pappas SG. Cost-Effectiveness of prolonged thromboprophylaxis after cancer surgery. Ann Surg Oncol. 2010:17:31-9.

Figueroa R, Alfonso A, Lopex-Picazo J, et al. Insights into venous thromboembolism prevention in hospitalized cancer patients: lessons from a prospective study. PLoS One. 2018:13:e0200220.

Hibbert PD, Hannaford NA, Hooper TD, et al. Assessing the appropriateness of prevention and management of venous thromboembolism in Australia: a cross-sectional study. BMJ Open. 2016;6:e008618.

Bump GM. How complete is the evidence for thromboembolism prophylaxis in general medicine patients? A meta-analysis of randomized controlled trials. J Hosp Med. 2009;4:289-97.

Budnik I, Brill A. Immune factors in deep vein thrombosis initiation. Trends Immunol. 2018;39:610-23.

Full Text: PDF


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.