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Semin Thromb Hemost 2014; 40(03): 395-400
DOI: 10.1055/s-0034-1370796
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thromboprophylaxis in Cancer Patients

Marc Carrier
1   Department of Medicine, The Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, Ontario, Canada
,
Agnes Y. Y. Lee
2   Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
› Author Affiliations
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Publication History

Publication Date:
05 March 2014 (online)

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Abstract

Cancer-associated thrombosis (CAT) is frequent and associated with significant morbidity and mortality among cancer patients. Hospitalized medically ill cancer patients are considered to be at high risk of CAT complications. Parenteral thromboprophylaxis with low-molecular-weight heparin is likely to reduce the risk of venous thromboembolism in this population and is recommended for the duration of the patient's hospitalization. Similarly, high-risk ambulatory cancer patients receiving chemotherapy should be made aware of their underlying risk and pharmacological thromboprophylaxis can be considered on a case-by-case basis in the absence of contraindication to anticoagulation.

Keywords

neoplasms - venous thromboembolism - venous thromboprophylaxis - heparin - low-molecular-weight heparin - bleeding
 

  • References

  • 1 Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res 2010; 125 (6) 490-493
    CrossrefPubMedSearch in Google Scholar
  • 2 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
    CrossrefPubMedSearch in Google Scholar
  • 3 Elting LS, Escalante CP, Cooksley C , et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med 2004; 164 (15) 1653-1661
    CrossrefPubMedSearch in Google Scholar
  • 4 Hutten BA, Prins MH, Gent M, Ginsberg JS, Tijssen JG, Büller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18 (17) 3078-3083
    CrossrefPubMedSearch in Google Scholar
  • 5 Prandoni P, Lensing AW, Piccioli A , et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
    CrossrefPubMedSearch in Google Scholar
  • 6 Stein PD, Beemath A, Meyers FA, Kayali F, Skaf E, Olson RE. Pulmonary embolism as a cause of death in patients who died with cancer. Am J Med 2006; 119 (2) 163-165
    CrossrefPubMedSearch in Google Scholar
  • 7 Anderson Jr FA, Zayaruzny M, Heit JA, Fidan D, Cohen AT. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol 2007; 82 (9) 777-782
    CrossrefPubMedSearch in Google Scholar
  • 8 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (6) 809-815
    CrossrefPubMedSearch in Google Scholar
  • 9 Kahn SR, Panju A, Geerts W , et al; CURVE study investigators Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res 2007; 119 (2) 145-155
    CrossrefPubMedSearch in Google Scholar
  • 10 Khorana AA, Francis CW, Culakova E, Fisher RI, Kuderer NM, Lyman GH. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 2006; 24 (3) 484-490
    CrossrefPubMedSearch in Google Scholar
  • 11 Khorana AA. The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease: strategies for improving VTE prophylaxis in hospitalized cancer patients. Oncologist 2007; 12 (11) 1361-1370
    CrossrefPubMedSearch in Google Scholar
  • 12 Levitan N, Dowlati A, Remick SC , et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 1999; 78 (5) 285-291
    CrossrefPubMedSearch in Google Scholar
  • 13 Cohen AT, Alikhan R, Arcelus JI , et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005; 94 (4) 750-759
    PubMedSearch in Google Scholar
  • 14 Kakkar AK, Levine M, Pinedo HM, Wolff R, Wong J. Venous thrombosis in cancer patients: insights from the FRONTLINE survey. Oncologist 2003; 8 (4) 381-388
    CrossrefPubMedSearch in Google Scholar
  • 15 Amin A, Stemkowski S, Lin J, Yang G. Thromboprophylaxis rates in US medical centers: success or failure?. J Thromb Haemost 2007; 5 (8) 1610-1616
    CrossrefPubMedSearch in Google Scholar
  • 16 Alikhan R, Cohen AT. Heparin for the prevention of venous thromboembolism in general medical patients (excluding stroke and myocardial infarction). Cochrane Database Syst Rev 2009; (3) CD003747
    PubMedSearch in Google Scholar
  • 17 Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146 (4) 278-288
    CrossrefPubMedSearch in Google Scholar
  • 18 Lloyd NS, Douketis JD, Moinuddin I, Lim W, Crowther MA. Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis. J Thromb Haemost 2008; 6 (3) 405-414
    CrossrefPubMedSearch in Google Scholar
  • 19 Mandalà M, Falanga A, Roila F. ESMO Guidelines Working Group. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2011; 22 (Suppl. 06) vi85-vi92
    CrossrefPubMedSearch in Google Scholar
  • 20 Lyman GH, Khorana AA, Kuderer NM , et al; American Society of Clinical Oncology Clinical Practice Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31 (17) 2189-2204
    CrossrefPubMedSearch in Google Scholar
  • 21 National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology Venous Thromboembolic Disease version 2.2011. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#supportive . Accessed Jan 10, 2012. National Comprehensive Cancer Network. 2013
    PubMedSearch in Google Scholar
  • 22 Samama MM, Cohen AT, Darmon JY , et al; Prophylaxis in Medical Patients with Enoxaparin Study Group A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999; 341 (11) 793-800
    CrossrefPubMedSearch in Google Scholar
  • 23 Leizorovicz A, Cohen AT, Turpie AGG, Olsson CG, Vaitkus PT, Goldhaber SZ ; PREVENT Medical Thromboprophylaxis Study Group Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110 (7) 874-879
    CrossrefPubMedSearch in Google Scholar
  • 24 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 (7537) 325-329
    CrossrefPubMedSearch in Google Scholar
  • 25 Carrier M, Moretto P, Le Gal G, Karp R, Zwicker JI. Lack of evidence to support thromboprophylaxis in hospitalized cancer patients. Am J Med 2014; 127 (1) 82-86
    CrossrefPubMedSearch in Google Scholar
  • 26 Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M ; PEGASUS investigators Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 2005; 92 (10) 1212-1220
    CrossrefPubMedSearch in Google Scholar
  • 27 Ajona D, Pajares MJ, Corrales L , et al. Investigation of complement activation product c4d as a diagnostic and prognostic biomarker for lung cancer. J Natl Cancer Inst 2013; 105 (18) 1385-1393
    CrossrefPubMedSearch in Google Scholar
  • 28 Corrales L, Ajona D, Rafail S , et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J Immunol 2012; 189 (9) 4674-4683
    CrossrefPubMedSearch in Google Scholar
  • 29 Mäkelä K, Helén P, Haapasalo H, Paavonen T. Complement activation in astrocytomas: deposition of C4d and patient outcome. BMC Cancer 2012; 12: 565
    CrossrefPubMedSearch in Google Scholar
  • 30 Maraveyas A, Waters J, Roy R , et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012; 48 (9) 1283-1292
    CrossrefPubMedSearch in Google Scholar
  • 31 Reiss H, Pelzer U, Deutschinoff G , et al. at: ASCO Annual Meeting Proceedings (Post-Meeting Edition). A prospective, randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC): Results of the CONKO 004 trial. J Clin Oncol 2009; 27 (18S) [Abstract]
    PubMedSearch in Google Scholar
  • 32 Gouin-Thibault I, Samama MM. Laboratory diagnosis of the thrombophilic state in cancer patients. Semin Thromb Hemost 1999; 25 (2) 167-172
    Thieme ConnectPubMedSearch in Google Scholar
  • 33 Traby L, Kaider A, Schmid R , et al. The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients. A randomised controlled trial. Thromb Haemost 2010; 104 (1) 92-99
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Desjardins L, Bara L, Boutitie F , et al. Correlation of plasma coagulation parameters with thromboprophylaxis, patient characteristics, and outcome in the MEDENOX study. Arch Pathol Lab Med 2004; 128 (5) 519-526
    PubMedSearch in Google Scholar
  • 35 Goldhaber SZ, Leizorovicz A, Kakkar AK , et al; ADOPT Trial Investigators Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365 (23) 2167-2177
    CrossrefPubMedSearch in Google Scholar
  • 36 Cohen AT, Spiro TE, Büller HR , et al; MAGELLAN Investigators Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368 (6) 513-523
    CrossrefPubMedSearch in Google Scholar
  • 37 Spencer FA, Lessard D, Emery C, Reed G, Goldberg RJ. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007; 167 (14) 1471-1475
    CrossrefPubMedSearch in Google Scholar
  • 38 Hull RD, Schellong SM, Tapson VF , et al; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153 (1) 8-18
    CrossrefPubMedSearch in Google Scholar
  • 39 Khorana AA, Dalal M, Tangirala K, Miao R. Higher Incidence of Venous Thromboembolism in the Outpatient Versus the Inpatient Setting Among U.S. Cancer Patients [Abstract]. Blood 2013; 118: 21
    PubMedSearch in Google Scholar
  • 40 Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104 (12) 2822-2829
    CrossrefPubMedSearch in Google Scholar
  • 41 Kuderer NM, Khorana AA, Francis CW, Culakova E, Ortel TL, Falanga A , et al. Venous Thromboembolism Risk Model Predicts Early Progression and Overall Mortality in Cancer Patients Receiving Chemotherapy [Abstract]. Blood 2008; 112: 11
    CrossrefPubMedSearch in Google Scholar
  • 42 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 2007; 5 (3) 632-634
    CrossrefPubMedSearch in Google Scholar
  • 43 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111 (10) 4902-4907
    CrossrefPubMedSearch in Google Scholar
  • 44 Moore RA, Adel N, Riedel E , et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 2011; 29 (25) 3466-3473
    CrossrefPubMedSearch in Google Scholar
  • 45 Mandala M, Clerici M, Corradino I , et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the 'SENDO experience'. Ann Oncol 2012; 23 (6) 1416-1421
    CrossrefPubMedSearch in Google Scholar
  • 46 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 (3) 291-292
    PubMedSearch in Google Scholar
  • 47 George D, Agnelli G, Fisher WD, Kakkar A, Lassen MR, Mismetti P , et al. Thromboembolism (VTE) prevention with semuloparin in cancer patients initiating chemotherapy: benefit-risk assessement by VTE risk in SAVE-ONCO [Abstract]. Blood 2011; 118: 206
    PubMedSearch in Google Scholar
  • 48 Ay C, Dunkler D, Marosi C , et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116 (24) 5377-5382
    CrossrefPubMedSearch in Google Scholar
  • 49 Hanna DL, White RH, Wun T. Biomolecular markers of cancer-associated thromboembolism. Crit Rev Oncol Hematol 2013; 88 (1) 19-29
    CrossrefPubMedSearch in Google Scholar
  • 50 Agnelli G, George DJ, Kakkar AK , et al; SAVE-ONCO Investigators Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366 (7) 601-609
    CrossrefPubMedSearch in Google Scholar
  • 51 Barni S, Labianca R, Agnelli G , et al. Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study. J Transl Med 2011; 9: 179
    CrossrefPubMedSearch in Google Scholar
  • 52 Riess H, Pelzer U, Hilbig A , et al. Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy). BMC Cancer 2008; 8: 361
    CrossrefPubMedSearch in Google Scholar
  • 53 Haas SK, Freund M, Heigener D , et al; TOPIC Investigators Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer. Clin Appl Thromb Hemost 2012; 18 (2) 159-165
    CrossrefPubMedSearch in Google Scholar
  • 54 Agnelli G, Gussoni G, Bianchini C , et al; PROTECHT Investigators Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009; 10 (10) 943-949
    CrossrefPubMedSearch in Google Scholar
  • 55 Verso M, Gussoni G, Agnelli G. Prevention of venous thromboembolism in patients with advanced lung cancer receiving chemotherapy: a combined analysis of the PROTECHT and TOPIC-2 studies. J Thromb Haemost 2010; 8 (7) 1649-1651
    CrossrefPubMedSearch in Google Scholar
  • 56 Perry JR, Julian JA, Laperriere NJ , et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost 2010; 8 (9) 1959-1965
    CrossrefPubMedSearch in Google Scholar
  • 57 Di Nisio M, Porreca E, Ferrante N, Otten HM, Cuccurullo F, Rutjes AW. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev 2012; 2: CD008500
    PubMedSearch in Google Scholar
  • 58 Levine MN, Gu C, Liebman HA , et al. A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer. J Thromb Haemost 2012; 10 (5) 807-814
    CrossrefPubMedSearch in Google Scholar