Best Practice & Research Clinical Haematology
Volume 22, Issue 1 , Pages 9-23 , March 2009

Epidemiology of cancer-related venous thromboembolism

  • Ted Wun, MD, FACP, Professor of Medicine

      Affiliations

    • Division of Hematology and Oncology, Departments of Internal Medicine and Pathology, Clinical and Translational Sciences Center (CTSC), University of California, Davis Cancer Center, 4501 X Street, Sacramento, CA 95187, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 916 734 3772; Fax: +1 916 734 7946.
    • ,
  • Richard H. White, MD, FACP, Professor of Medicine

      Affiliations

    • Division of General Internal Medicine, Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA

References 

  1. Sorensen HT, Mellemkjaer L, Olsen JH, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343:1846–1850
  2. Alcalay A, Wun T, Khatri V, et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol. 2006;24:1112–1118
  3. 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;166:458–464
  4. Rodriguez AO, Wun T, Chew H, et al. Venous thromboembolism in ovarian cancer. Gynecol Oncol. 2007;105:784–790
  5. Semrad TJ, O'Donnell R, Wun T, et al. Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg. 2007;106:601–608
  6. White RH, Zhou H, Murin S, et al. Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost. 2005;93:298–305
  7. Heit JA, O'Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med. 2002;162:1245–1248
  8. Buller HR, van Doormaal FF, van Sluis GL, et al. Cancer and thrombosis: from molecular mechanisms to clinical presentations. J Thromb Haemost. 2007;5(Suppl. 1):246–254
  9. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood. 2007;110:1723–1729
  10. Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Assoc. 2005;293:715–722
  11. Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005;6:401–410
  12. Rickles FR, Levine MN. Epidemiology of thrombosis in cancer. Acta Haematol. 2001;106:6–12
  13. Hansson PO, Welin L, Tibblin G, et al. Deep vein thrombosis and pulmonary embolism in the general population. ‘The Study of Men Born in 1913’. Arch Intern Med. 1997;157:1665–1670
  14. Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost. 2002;87:575–579
  15. DeMonaco NA, Dang Q, Kapoor WN, et al. Pulmonary embolism incidence is increasing with use of spiral computed tomography. Am J Med. 2008;121:611–617
  16. Satoh T, Matsumoto K, Uno K, et al. Silent venous thromboembolism before treatment in endometrial cancer and the risk factors. Br J Cancer. 2008 Oct 7;99(7):1034–1039
  17. Satoh T, Oki A, Uno K, et al. High incidence of silent venous thromboembolism before treatment in ovarian cancer. Br J Cancer. 2007;97:1053–1057
  18. O'Connell CL, Boswell WD, Duddalwar V, et al. Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance. J Clin Oncol. 2006;24:4928–4932
  19. Cronin CG, Lohan DG, Keane M, et al. Prevalence and significance of asymptomatic venous thromboembolic disease found on oncologic staging CT. AJR Am J Roentgenol. 2007;189:162–170
  20. El Accaoui RN, Shamseddeen WA, Taher AT. Thalidomide and thrombosis. A meta-analysis. Thromb Haemost. 2007;97:1031–1036
  21. Blom JW, Vanderschoot JP, Oostindier MJ, et al. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost. 2006;4:529–535
  22. 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;78:285–291
  23. White RH, Wun T. The burden of cancer-associated venous thromboembolism and its impact on cancer survival. In:  Khorana AA,  Francis CW editor. Cancer-associated thrombosis: new findings in translational science, prevention, and treatment. New York: Informa Healthcare, USA, Inc.; 2008;
  24. Chew HK, Davies AM, Wun T, et al. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost. 2008;6:601–608
  25. Chew HK, Wun T, Harvey DJ, et al. Incidence of venous thromboembolism and the impact on survival in breast cancer patients. J Clin Oncol. 2007;25:70–76
  26. Falanga A, Rickles FR. Pathophysiology of the thrombophilic state in the cancer patient. Semin Thromb Hemost. 1999;25:173–182
  27. Elliott MA, Wolf RC, Hook CC, et al. Thromboembolism in adults with acute lymphoblastic leukemia during induction with L-asparaginase-containing multi-agent regimens: incidence, risk factors, and possible role of antithrombin. Leuk Lymphoma. 2004;45:1545–1549
  28. Wun T, Chew HK, Zhou H, et al. Cause of death among patients with local or regional stage cancer of the breast, colon and lung who develop venous thromboembolism (VTE). Blood. 2006;108:433a
  29. Wun T, Chew H, Zhou H, et al. Venous thromboembolism (VTE) is associated with recurrent cancer in patients with initially non-metastatic breast, lung, and colon cancer. Thromb Res. 2007;120:S175
  30. Extermann M. Interaction between comorbidity and cancer. Cancer Control. 2007;14:13–22
  31. Kendal WS. Dying with cancer: the influence of age, comorbidity, and cancer site. Cancer. 2008;112:1354–1362
  32. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003;90:446–455
  33. Prandoni P, Piccioli A, Girolami A. Cancer and venous thromboembolism: an overview. Haematologica. 1999;84:437–445
  34. Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. J Am Med Assoc. 2004;291:2441–2447
  35. Charlson M, Szatrowski TP, Peterson J, et al. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–1251
  36. Elixhauser A, Steiner C, Harris DR, et al. Comorbidity measures for use with administrative data. Med Care. 1998;36:8–27
  37. 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;164:190–194
  38. Lee AY, Levine MN. The thrombophilic state induced by therapeutic agents in the cancer patient. Semin Thromb Hemost. 1999;25:137–145
  39. Khorana AA, Francis CW, Culakova E, et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer. 2005;104:2822–2829
  40. Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res. 2006;118:555–568
  41. Alkindi S, Dennison D, Pathare A. Arterial and venous thrombotic complications with thalidomide in multiple myeloma. Arch Med Res. 2008;39:257–258
  42. Hirsh J. Risk of thrombosis with lenalidomide and its prevention with aspirin. Chest. 2007;131:275–277
  43. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22:414–423
  44. Kilickap S, Abali H, Celik I. Bevacizumab, bleeding, thrombosis, and warfarin. J Clin Oncol. 2003;21:3542;author reply 3543
  45. 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. J Am Med Assoc. 2008;299:914–924
  46. Wun T, Law L, Harvey D, et al. Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation, and erythropoietin. Cancer. 2003;98:1514–1520
  47. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006;98:708–714
  48. Lavey RS, Liu PY, Greer BE, et al. Recombinant human erythropoietin as an adjunct to radiation therapy and cisplatin for stage IIB-IVA carcinoma of the cervix: a Southwest Oncology Group study. Gynecol Oncol. 2004;95:145–151
  49. Khorana AA, Francis CW, Culakova E, et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 2007;110:2339–2346
  50. Verso M, Agnelli G. Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. J Clin Oncol. 2003;21:3665–3675
  51. Verso M, Agnelli G, Bertoglio S, et al. Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients. J Clin Oncol. 2005;23:4057–4062
  52. Mismetti P, Mille D, Laporte S, et al. Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial. Haematologica. 2003;88:67–73
  53. Niers TM, Di Nisio M, Klerk CP, et al. Prevention of catheter-related venous thrombosis with nadroparin in patients receiving chemotherapy for hematologic malignancies: a randomized, placebo-controlled study. J Thromb Haemost. 2007;5:1878–1882
  54. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902–4907
  55. Falanga A. The predictive value of D-dimer measurement for cancer in patients with deep vein thrombosis. Haematologica. 2005;90:149
  56. Kroger K, Weiland D, Ose C, et al. Risk factors for venous thromboembolic events in cancer patients. Ann Oncol. 2006;17:297–303
  57. Chen M, Geng JG. P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp. 2006;54:75–84
  58. Ay C, Simanek R, Vormittag R, et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood. 2008;112:2703–2708
  59. Tesselaar ME, Romijn FP, Van Der Linden IK, et al. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?. Thromb Haemost. 2007;5:520–527
  60. 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;100:3484–3488
  61. Bona RD, Hickey AD, Wallace DM. Efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost. 1997;78:137–140
  62. Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000;160:761–768
  63. Hutten BA, Prins MH, Gent M, et al. 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;18:3078–3083
  64. Green D, Hull RD, Brant R, et al. Lower mortality in cancer patients treated with low-molecular-weight versus standard heparin. Lancet. 1992;339:1476
  65. Gould MK, Dembitzer AD, Doyle RL, et al. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med. 1999;130:800–809
  66. Hettiarachchi RJ, Smorenburg SM, Ginsberg J, et al. Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost. 1999;82:947–952
  67. Smorenburg SM, Hettiarachchi RJ, Vink R, et al. The effects of unfractionated heparin on survival in patients with malignancy – a systematic review. Thromb Haemost. 1999;82:1600–1604
  68. Siragusa S, Cosmi B, Piovella F, et al. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med. 1996;100:269–277
  69. 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;22:1944–1948
  70. Lee AY, Rickles FR, Julian JA, et al. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005;23:2123–2129
  71. Sgouros J, Maraveyas A. Excess premature (3-month) mortality in advanced pancreatic cancer could be related to fatal vascular thromboembolic events. A hypothesis based on a systematic review of phase III chemotherapy studies in advanced pancreatic cancer. Acta Oncol. 2008;47(3):337–346
  72. 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;2:1266–1271
  73. Khorana AA, Francis CW, Culakova E, et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5:632–634
  74. Lee AY. Deep vein thrombosis and cancer: survival, recurrence, and anticoagulant choices. Disease-a-month. 2005;51:150–157

PII: S1521-6926(08)00106-0

doi: 10.1016/j.beha.2008.12.001

Best Practice & Research Clinical Haematology
Volume 22, Issue 1 , Pages 9-23 , March 2009

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