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Semin Thromb Hemost 2012; 38(08): 759-767
DOI: 10.1055/s-0032-1328893
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thromboprophylaxis Guidelines in Cancer with a Primary Focus on Ambulatory Patients Receiving Chemotherapy: A Review from the Southern Network on Adverse Reactions (SONAR)

Whitney D. Maxwell
1   South Carolina College of Pharmacy, Columbia, South Carolina
,
Charles L. Bennett
1   South Carolina College of Pharmacy, Columbia, South Carolina
2   Arnold School of Public Health of the University of South Carolina, Columbia, South Carolina
3   Hollings Cancer Center of the Medical University of South Carolina, Charleston, South Carolina
4   WJB Dorn VA Medical Center, Columbia, South Carolina
5   South Carolina Center of Economic Excellence for Medical Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR), South Carolina College of Pharmacy, Columbia, South Carolina
› Author Affiliations
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Publication History

Publication Date:
30 October 2012 (online)

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Abstract

Patients with cancer are at increased risk for venous thromboembolism (VTE). Factors related to cancer type, site, stage, duration, and extent of disease contribute to the oncology patient's risk of VTE. Patient-specific factors such as history of prior VTE and comorbidity are also contributory. The role of treatment-related factors, including chemotherapy regimen, has been a focus of recent investigation because most cases of VTE in the oncology setting occur in ambulatory patients. Thus, an emerging area of clinical research is primary VTE prophylaxis in the ambulatory cancer setting. Clinical guidelines currently recommend primary thromboprophylaxis in cancer patients who are undergoing surgery, who are hospitalized, and who are in a specific subset of high-risk ambulatory cancer patients. Validated risk stratification tools are essential for identification of patients who are at high risk of thrombosis. Emerging data from recently published clinical trials, as well as ongoing studies, are likely to advance our understanding of the potential utility of antithrombotic agents for primary prophylaxis in ambulatory patients with cancer and may influence future clinical guideline recommendations.

Keywords

anticoagulants - chemotherapy - cancer - venous thromboembolism - thromboprophylaxis
 

  • References

  • 1 Streiff MB, Bockenstedt PL, Cataland SR , et al. Venous thromboembolic disease. J Natl Compr Canc Netw 2011; 9 (7) 714-777
    PubMedGoogle Scholar
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (6) 715-722
    CrossrefPubMedGoogle Scholar
  • 5 Spencer FA, Lessard D, Emery C, Reed G, Goldberg RJ. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007; 167 (14) 1471-1475
    CrossrefPubMedGoogle Scholar
  • 6 Imberti D, Agnelli G, Ageno W , et al. Clinical characteristics and management of cancer-associated acute venous thromboembolism: findings from the MASTER Registry. Haematologica 2008; 93 (2) 273-278
    CrossrefPubMedGoogle Scholar
  • 7 Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166 (4) 458-464
    CrossrefPubMedGoogle Scholar
  • 8 Lyman GH, Khorana AA, Falanga A , et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007; 25 (34) 5490-5505
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Sood SL. Cancer-associated thrombosis. Curr Opin Hematol 2009; 16 (5) 378-385
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 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
    CrossrefPubMedGoogle Scholar
  • 13 Otten HM, Mathijssen J, ten Cate H , et al. Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med 2004; 164 (2) 190-194
    CrossrefPubMedGoogle Scholar
  • 14 Bennett CL, Schumock GT, Desai AA , et al. Thalidomide-associated deep vein thrombosis and pulmonary embolism. Am J Med 2002; 113 (7) 603-606
    CrossrefPubMedGoogle Scholar
  • 15 Bennett CL, Angelotta C, Yarnold PR , et al. Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer. JAMA 2006; 296 (21) 2558-2560
    PubMedGoogle Scholar
  • 16 Deitcher SR, Gomes MP. The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma: a systematic review. Cancer 2004; 101 (3) 439-449
    CrossrefPubMedGoogle Scholar
  • 17 Bennett CL, Silver SM, Djulbegovic B , et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008; 299 (8) 914-924
    CrossrefPubMedGoogle Scholar
  • 18 Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300 (19) 2277-2285
    CrossrefPubMedGoogle Scholar
  • 19 Hurwitz HI, Saltz LB, Van Cutsem E , et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol 2011; 29 (13) 1757-1764
    CrossrefPubMedGoogle Scholar
  • 20 den Exter PL, Hooijer J, Dekkers OM, Huisman MV. Risk of recurrent venous thromboembolism and mortality in patients with cancer incidentally diagnosed with pulmonary embolism: a comparison with symptomatic patients. J Clin Oncol 2011; 29 (17) 2405-2409
    CrossrefPubMedGoogle Scholar
  • 21 Di Nisio M, Ferrante N, De Tursi M , et al. Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Thromb Haemost 2010; 104 (5) 1049-1054
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Dentali F, Ageno W, Becattini C , et al. Prevalence and clinical history of incidental, asymptomatic pulmonary embolism: a meta-analysis. Thromb Res 2010; 125 (6) 518-522
    CrossrefPubMedGoogle Scholar
  • 23 Browne AM, Cronin CG, English C, Ni Mhuircheartaigh J, Murphy JM, Bruzzi JF. Unsuspected pulmonary emboli in oncology patients undergoing routine computed tomography imaging. J Thorac Oncol 2010; 5 (6) 798-803
    CrossrefPubMedGoogle Scholar
  • 24 Kahn SR, Lim W, Dunn AS , et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl) e195S-e226S
    CrossrefPubMedGoogle Scholar
  • 25 Gould MK, Garcia DA, Wren SM , et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl) e227S-e277S
    CrossrefPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Wright JD, Lewin SN, Shah M , et al. Quality of venous thromboembolism prophylaxis in patients undergoing oncologic surgery. Ann Surg 2011; 253 (6) 1140-1146
    CrossrefPubMedGoogle Scholar
  • 28 Abdel-Razeq H, Albadainah F, Hijjawi S, Mansour A, Treish I. Venous thromboembolism (VTE) in hospitalized cancer patients: prophylaxis failure or failure to prophylax!. J Thromb Thrombolysis 2011; 31 (1) 107-112
    CrossrefPubMedGoogle Scholar
  • 29 Kucher N, Spirk D, Baumgartner I , et al. Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER). Ann Oncol 2010; 21 (5) 931-935
    CrossrefPubMedGoogle Scholar
  • 30 Trujillo-Santos J, Nieto JA, Ruíz-Gamietea A , et al. Bleeding complications associated with anticoagulant therapy in patients with cancer. Thromb Res 2010; 125 (Suppl. 02) S58-S61
    CrossrefPubMedGoogle Scholar
  • 31 Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl) e24S-e43S
    CrossrefPubMedGoogle Scholar
  • 32 Ay C, Dunkler D, Marosi C , et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116 (24) 5377-5382
    CrossrefPubMedGoogle Scholar
  • 33 Ay C, Dunkler D, Simanek R , et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2011; 29 (15) 2099-2103
    CrossrefPubMedGoogle Scholar
  • 34 Geerts WH, Bergqvist D, Pineo GF , et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest 2008; 133 (6 Suppl) 381S-453S
    CrossrefPubMedGoogle Scholar
  • 35 Levine M, Hirsh J, Gent M , et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994; 343 (8902) 886-889
    CrossrefPubMedGoogle Scholar
  • 36 Palumbo A, Cavo M, Bringhen S , et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol 2011; 29 (8) 986-993
    CrossrefPubMedGoogle Scholar
  • 37 Baz R, Li L, Kottke-Marchant K , et al. The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma. Mayo Clin Proc 2005; 80 (12) 1568-1574
    CrossrefPubMedGoogle Scholar
  • 38 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
    CrossrefPubMedGoogle Scholar
  • 39 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
    CrossrefPubMedGoogle Scholar
  • 40 Agnelli G, Gussoni G, Bianchini C , et al. 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
    CrossrefPubMedGoogle Scholar
  • 41 Agnelli G, George DJ, Kakkar AK , et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366 (7) 601-609
    CrossrefPubMedGoogle Scholar
  • 42 Haas SK, Freund M, Heigener D , et al. 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
    CrossrefPubMedGoogle Scholar
  • 43 Lebeau B, Chastang C, Brechot JM , et al. Subcutaneous heparin treatment increases survival in small cell lung cancer. “Petites Cellules” Group. Cancer 1994; 74 (1) 38-45
    CrossrefPubMedGoogle Scholar
  • 44 Altinbas M, Coskun HS, Er O , et al. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost 2004; 2 (8) 1266-1271
    CrossrefPubMedGoogle Scholar
  • 45 Kakkar AK, Levine MN, Kadziola Z , et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the Fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 2004; 22 (10) 1944-1948
    CrossrefPubMedGoogle Scholar
  • 46 Sideras K, Schaefer PL, Okuno SH , et al. Low-molecular-weight heparin in patients with advanced cancer: a phase 3 clinical trial. Mayo Clin Proc 2006; 81 (6) 758-767
    CrossrefPubMedGoogle Scholar
  • 47 Akl EA, Schünemann HJ. Routine heparin for patients with cancer? One answer, more questions. N Engl J Med 2012; 366 (7) 661-662
    CrossrefPubMedGoogle Scholar