Risk Factors for Thrombosis in Cancer Patients

  • Aneel A. Ashrani
  • John A. Heit
Part of the Cancer Treatment and Research book series (CTAR, volume 148)

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and its complication, pulmonary embolism (PE), is a multifactorial disease, involving complex interactions between environmental exposures and patients, including their hemostatic system and genetic predispositions. VTE is relatively common, with an overall average age- and sex-adjusted incidence of about 1.04–1.9 per 1000 person-years that rises dramatically with increasing age [1–4]. Active malignancy accounts for almost 20% of incident VTE events occurring in the community [5], and imparts a 4- to 6.5-fold higher VTE risk compared to non-cancer patients, depending on concurrent use of anti-cancer therapy [6]. The risk of VTE also varies by cancer type and stage [7–10]. The association between VTE and malignancy has been recognized since 1861 when Trousseau, in a lecture, described thrombophlebitis as the presenting sign of visceral malignancy [11].


Polycythemia Vera Essential Thrombocythemia JAK2 V617F Factor Versus Leiden Mutation Thrombin Activatable Fibrinolysis Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ III. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998 Mar 23;158(6):585–93.PubMedGoogle Scholar
  2. 2.
    Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004 Jul 1;117(1):19–25.PubMedGoogle Scholar
  3. 3.
    Spencer FA, Emery C, Lessard D, Anderson F, Emani S, Aragam J, et al. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med. 2006 Jul;21(7):722–7.PubMedGoogle Scholar
  4. 4.
    Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrom J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007 Apr;5(4):692–9.PubMedGoogle Scholar
  5. 5.
    Heit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med. 2002 Jun 10;162(11):1245–8.PubMedGoogle Scholar
  6. 6.
    Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ III. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000 Mar 27;160(6):809–15.PubMedGoogle Scholar
  7. 7.
    Heit JA, Petterson TM, Marks RS, Bailey KR, Melton LJ III. The risk of venous thromboembolism (VTE) among cancer patients by tumor site: a population-based study. Blood (ASH Annual Meeting Abstracts). 2004 November 16, 2004;104(11):2596.Google Scholar
  8. 8.
    Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. Jama. 2005 Feb 9;293(6):715–22.PubMedGoogle Scholar
  9. 9.
    Blom JW, Vanderschoot JP, Oostindier MJ, Osanto S, van der Meer FJ, Rosendaal FR. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost. 2006 Mar;4(3):529–35.PubMedGoogle Scholar
  10. 10.
    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 Feb 27;166(4):458–64.PubMedGoogle Scholar
  11. 11.
    Trousseau A. Phlegmasia alba dolens. In: Cormack JR, ed. Lectures on clinical medicine. London: The New Sydenham Society 1872:281–332.Google Scholar
  12. 12.
    Prandoni P, Lensing AW, Buller HR, Cogo A, Prins MH, Cattelan AM, et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med. 1992 Oct 15;327(16):1128–33.PubMedGoogle Scholar
  13. 13.
    Baron JA, Gridley G, Weiderpass E, Nyren O, Linet M. Venous thromboembolism and cancer. Lancet. 1998 Apr 11;351(9109):1077–80.PubMedGoogle Scholar
  14. 14.
    Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial. N Engl J Med. 2000 Jun 29;342(26):1953–8.PubMedGoogle Scholar
  15. 15.
    Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000 Dec 21;343(25):1846–50.PubMedGoogle Scholar
  16. 16.
    White RH, Chew HK, Zhou H, Parikh-Patel A, Harris D, Harvey D, et al. Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528,693 adults. Archives of internal medicine. 2005 Aug 8–22;165(15):1782–7.PubMedGoogle Scholar
  17. 17.
    Lee AY. Screening for occult cancer in patients with idiopathic venous thromboembolism: no. J Thromb Haemost. 2003 Nov;1(11):2273–4.PubMedGoogle Scholar
  18. 18.
    Piccioli A, Prandoni P. Screening for occult cancer in patients with idiopathic venous thromboembolism: yes. J Thromb Haemost. 2003 Nov;1(11):2271–2.PubMedGoogle Scholar
  19. 19.
    Piccioli A, Lensing AW, Prins MH, Falanga A, Scannapieco GL, Ieran M, et al. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost. 2004 Jun;2(6):884–9.PubMedGoogle Scholar
  20. 20.
    Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R, 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 Sep;78(5):285–91.Google Scholar
  21. 21.
    Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller 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 Sep;18(17):3078–83.PubMedGoogle Scholar
  22. 22.
    Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002 Nov 15;100(10):3484–8.PubMedGoogle Scholar
  23. 23.
    Ambrus JL, Ambrus CM, Mink IB, Pickren JW. Causes of death in cancer patients. J Med. 1975;6(1):61–4.PubMedGoogle Scholar
  24. 24.
    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 Mar;5(3):632–4.PubMedGoogle Scholar
  25. 25.
    Heit JA, Melton LJ III, Lohse CM, Petterson TM, Silverstein MD, Mohr DN, et al. Incidence of venous thromboembolism in hospitalized patients vs community residents. Mayo Clin Proc. 2001 Nov;76(11):1102–10.Google Scholar
  26. 26.
    White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003 Sep;90(3):446–55.PubMedGoogle Scholar
  27. 27.
    Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, et al. Prevention of venous thromboembolism: 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):338S–400S.PubMedGoogle Scholar
  28. 28.
    White RH, Gettner S, Newman JM, Trauner KB, Romano PS. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med. 2000 Dec 14;343(24):1758–64.PubMedGoogle Scholar
  29. 29.
    Heit JA. Venous thromboembolism: disease burden, outcomes and risk factors. J Thromb Haemost. 2005 Aug;3(8):1611–7.PubMedGoogle Scholar
  30. 30.
    Sharrock NE, Haas SB, Hargett MJ, Urquhart B, Insall JN, Scuderi G. Effects of epidural anesthesia on the incidence of deep-vein thrombosis after total knee arthroplasty. J Bone Joint Surg. 1991 Apr;73(4):502–6.PubMedGoogle Scholar
  31. 31.
    Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A, et al. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med. 2004 May 10;164(9):963–8.PubMedGoogle Scholar
  32. 32.
    Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score. J Thromb Haemost. 2004 Dec;2(12):2156–61.PubMedGoogle Scholar
  33. 33.
    Dalen JE. Economy class syndrome: too much flying or too much sitting? Arch Intern Med. 2003 Dec 8–22;163(22):2674–6.PubMedGoogle Scholar
  34. 34.
    Chee YL, Watson HG. Air travel and thrombosis. Br J Haematol. 2005 Sep;130(5):671–80.PubMedGoogle Scholar
  35. 35.
    Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med. 2004 Oct 11;164(18):1965–76.PubMedGoogle Scholar
  36. 36.
    Rosendaal FR. Risk factors for venous thrombotic disease. Thromb Haemost. 1999;82(2):610–9.PubMedGoogle Scholar
  37. 37.
    Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ I. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005 Nov 15;143(10):697–706.PubMedGoogle Scholar
  38. 38.
    Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects. Arch Intern Med. 2000 Jan 10;160(1):49–52.PubMedGoogle Scholar
  39. 39.
    Curb JD, Prentice RL, Bray PF, Langer RD, Van Horn L, Barnabei VM, et al. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch Intern Med. 2006 Apr 10;166(7):772–80.PubMedGoogle Scholar
  40. 40.
    Scarabin PY, Oger E, Plu-Bureau G. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003 Aug 9;362(9382):428–32.PubMedGoogle Scholar
  41. 41.
    Straczek C, Oger E, Yon de Jonage-Canonico MB, Plu-Bureau G, Conard J, Meyer G, et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation. 2005 Nov 29;112(22):3495–500.PubMedGoogle Scholar
  42. 42.
    Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Rosendaal FR, et al. Conjugated equine estrogen, esterified estrogen, prothrombotic variants, and the risk of venous thrombosis in postmenopausal women. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2807–12.PubMedGoogle Scholar
  43. 43.
    Heit J, Farmer S, Petterson T, Bailey K, Melton L III. Novel risk factors for venous thromboembolism: a population-based, case-control study. Blood. 2005;106(11):463a (Abstract #1618).Google Scholar
  44. 44.
    Meier CR, Jick H. Tamoxifen and risk of idiopathic venous thromboembolism. Br J Clin Pharmacol. 1998 Jun;45(6):608–12.PubMedGoogle Scholar
  45. 45.
    Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple outcomes of raloxifene evaluation. JAMA. 1999 Jun 16;281(23):2189–97.PubMedGoogle Scholar
  46. 46.
    Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia A, et al. Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation. Obstet Gynecol. 2004 Oct;104(4):837–44.PubMedGoogle Scholar
  47. 47.
    Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med. 2006 Aug 24;355(8):809–17.PubMedGoogle Scholar
  48. 48.
    Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. J Am Soc Nephrol. 2007 Aug;18(8):2221–5.PubMedGoogle Scholar
  49. 49.
    Ray JG, Burows RF, Ginsberg JS, Burrows EA. Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: review and recommendations for management of the pregnant and nonpregnant patient. Haemostasis. 2000 May-Jun;30(3):103–17.PubMedGoogle Scholar
  50. 50.
    Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007 May;137(3):181–92.PubMedGoogle Scholar
  51. 51.
    Yarranton H, Cohen H, Pavord SR, Benjamin S, Hagger D, Machin SJ. Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura. Br J Haematol. 2003 Jun;121(5):778–85.PubMedGoogle Scholar
  52. 52.
    Sarica-Kucukoglu R, Akdag-Kose A, Kayabal IM, Yazganoglu KD, Disci R, Erzengin D, et al. Vascular involvement in Behcet's disease: a retrospective analysis of 2319 cases. Int J Ddermatol. 2006 Aug;45(8):919–21.Google Scholar
  53. 53.
    Calvo-Alen J, Toloza SM, Fernandez M, Bastian HM, Fessler BJ, Roseman JM, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients. Arthritis Rheu. 2005 Jul;52(7):2060–8.Google Scholar
  54. 54.
    Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Allen NB, Davis JC Jr, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med. 2005 Apr 19;142(8):620–6.PubMedGoogle Scholar
  55. 55.
    Srirajaskanthan R, Winter M, Muller AF. Venous thrombosis in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2005 Jul;17(7):697–700.PubMedGoogle Scholar
  56. 56.
    Cattaneo M. Hyperhomocysteinemia and venous thromboembolism. Semin Thromb Hemost. 2006 Oct;32(7):716–23.PubMedGoogle Scholar
  57. 57.
    Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med. 2007 Jun;131(6):872–84.PubMedGoogle Scholar
  58. 58.
    McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969 Jul;56(1):111–28.PubMedGoogle Scholar
  59. 59.
    Tsai AW, Cushman M, Tsai MY, Heckbert SR, Rosamond WD, Aleksic N, et al. Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE). Am J Hematol. 2003 Mar;72(3):192–200.PubMedGoogle Scholar
  60. 60.
    Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost. 2005 Feb;3(2):292–9.Google Scholar
  61. 61.
    Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E. Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial. Ann Intern Med. 2007 Jun 5;146(11):761–7.PubMedGoogle Scholar
  62. 62.
    den Heijer M, Willems HP, Blom HJ, Gerrits WB, Cattaneo M, Eichinger S, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood. 2007 Jan 1;109(1):139–44.Google Scholar
  63. 63.
    Souto JC, Almasy L, Borrell M, Blanco-Vaca F, Mateo J, Soria JM, et al. Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic Analysis of Idiopathic Thrombophilia. Am J Hum Genet. 2000 Dec;67(6):1452–9.PubMedGoogle Scholar
  64. 64.
    Larsen TB, Sorensen HT, Skytthe A, Johnsen SP, Vaupel JW, Christensen K. Major genetic susceptibility for venous thromboembolism in men: a study of Danish twins. Epidemiology, Cambridge, Mass. 2003 May;14(3):328–32.Google Scholar
  65. 65.
    Heit JA, Phelps MA, Ward SA, Slusser JP, Petterson TM, De Andrade M. Familial segregation of venous thromboembolism. J Thromb Haemost. 2004 May;2(5):731–6.PubMedGoogle Scholar
  66. 66.
    Sanson BJ, Simioni P, Tormene D, Moia M, Friederich PW, Huisman MV, et al. The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study. Blood. 1999 Dec 1;94(11):3702–6.PubMedGoogle Scholar
  67. 67.
    Folsom AR, Aleksic N, Wang L, Cushman M, Wu KK, White RH. Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study. Arterioscler, Thromb Vasc Biol. 2002 Jun 1;22(6):1018–22.Google Scholar
  68. 68.
    Vossen CY, Rosendaal FR. The protective effect of the factor XIII Val34Leu mutation on the risk of deep venous thrombosis is dependent on the fibrinogen level. J Thromb Haemost. 2005 May;3(5):1102–3.PubMedGoogle Scholar
  69. 69.
    Bombeli T, Piccapietra B, Boersma J, Fehr J. Decreased anticoagulant response to tissue factor pathway inhibitor in patients with venous thromboembolism and otherwise no evidence of hereditary or acquired thrombophilia. Thromb Haemost. 2004 Jan;91(1):80–6.PubMedGoogle Scholar
  70. 70.
    Yin ZF, Huang ZF, Cui J, Fiehler R, Lasky N, Ginsburg D, et al. Prothrombotic phenotype of protein Z deficiency. Proc Natl Acad Sci USA. 2000 Jun 6;97(12):6734–8.Google Scholar
  71. 71.
    Santacroce R, Sarno M, Cappucci F, Sessa F, Colaizzo D, Brancaccio V, et al. Low protein Z levels and risk of occurrence of deep vein thrombosis. J Thromb Haemost. 2006 Nov;4(11):2417–22.PubMedGoogle Scholar
  72. 72.
    Uitte de Willige S, de Visser MC, Houwing–Duistermaat JJ, Rosendaal FR, Vos HL, Bertina RM. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood. 2005 Dec 15;106(13):4176–83.PubMedGoogle Scholar
  73. 73.
    Price DT, Ridker PM. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med. 1997 Nov 15;127(10):895–903.PubMedGoogle Scholar
  74. 74.
    Folsom AR, Cushman M, Tsai MY, Aleksic N, Heckbert SR, Boland LL, et al. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood. 2002 Apr 15;99(8):2720–5.PubMedGoogle Scholar
  75. 75.
    Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med. 2003 Jan 21;138(2):128–34.PubMedGoogle Scholar
  76. 76.
    Heit JA, Sobell JL, Li H, Sommer SS. The incidence of venous thromboembolism among Factor V Leiden carriers: a community-based cohort study. J Thromb Haemost. 2005 Feb;3(2):305–11.PubMedGoogle Scholar
  77. 77.
    Chandler WL, Rodgers GM, Sprouse JT, Thompson AR. Elevated hemostatic factor levels as potential risk factors for thrombosis. Arch Pathol Lab Med. 2002 Nov;126(11):1405–14.PubMedGoogle Scholar
  78. 78.
    Folsom AR, Cushman M, Tsai MY, Heckbert SR, Aleksic N. Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism. Am J Hematol. 2002 Dec;71(4):285–90.PubMedGoogle Scholar
  79. 79.
    Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995 Jan 21;345(8943):152–5.PubMedGoogle Scholar
  80. 80.
    Kraaijenhagen RA, in't Anker PS, Koopman MM, Reitsma PH, Prins MH, van den Ende A, et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost. 2000 Jan;83(1):5–9.PubMedGoogle Scholar
  81. 81.
    Bank I, Libourel EJ, Middeldorp S, Hamulyak K, van Pampus EC, Koopman MM, et al. Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost. 2005 Jan;3(1):79–84.PubMedGoogle Scholar
  82. 82.
    van Hylckama Vlieg A, van der Linden IK, Bertina RM, Rosendaal FR. High levels of factor IX increase the risk of venous thrombosis. Blood. 2000 Jun 15;95(12):3678–82.PubMedGoogle Scholar
  83. 83.
    Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000 Mar 9;342(10):696–701.PubMedGoogle Scholar
  84. 84.
    Cushman M, Folsom AR, Wang L, Aleksic N, Rosamond WD, Tracy RP, et al. Fibrin fragment D-dimer and the risk of future venous thrombosis. Blood. 2003 Feb 15;101(4):1243–8.PubMedGoogle Scholar
  85. 85.
    Tripodi A, Chantarangkul V, Martinelli I, Bucciarelli P, Mannucci PM. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood. 2004 Dec 1;104(12):3631–4.PubMedGoogle Scholar
  86. 86.
    Lisman T, de Groot PG, Meijers JC, Rosendaal FR. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood. 2005 Feb 1;105(3):1102–5.PubMedGoogle Scholar
  87. 87.
    Cicala C, Cirino G. Linkage between inflammation and coagulation: an update on the molecular basis of the crosstalk. Life Sci. 1998;62(20):1817–24.PubMedGoogle Scholar
  88. 88.
    Andre P, Hartwell D, Hrachovinova I, Saffaripour S, Wagner DD. Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci USA. 2000 Dec 5;97(25):13835–40.Google Scholar
  89. 89.
    Myers DD, Hawley AE, Farris DM, Wrobleski SK, Thanaporn P, Schaub RG, et al. P-selectin and leukocyte microparticles are associated with venous thrombogenesis. J Vasc Surg. 2003 Nov;38(5):1075–89.PubMedGoogle Scholar
  90. 90.
    Reitsma PH, Rosendaal FR. Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia Study. J Thromb Haemost. 2004 Apr;2(4):619–22.PubMedGoogle Scholar
  91. 91.
    Chirinos JA, Heresi GA, Velasquez H, Jy W, Jimenez JJ, Ahn E, et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol. 2005 May 3;45(9):1467–71.PubMedGoogle Scholar
  92. 92.
    de Lange M, Snieder H, Ariens RA, Spector TD, Grant PJ. The genetics of haemostasis: a twin study. Lancet. 2001 Jan 13;357(9250):101–5.PubMedGoogle Scholar
  93. 93.
    Ariens RA, de Lange M, Snieder H, Boothby M, Spector TD, Grant PJ. Activation markers of coagulation and fibrinolysis in twins: heritability of the prethrombotic state. Lancet. 2002 Feb 23;359(9307):667–71.PubMedGoogle Scholar
  94. 94.
    Vossen CY, Hasstedt SJ, Rosendaal FR, Callas PW, Bauer KA, Broze GJ, et al. Heritability of plasma concentrations of clotting factors and measures of a prethrombotic state in a protein C-deficient family. J Thromb Haemost. 2004 Feb;2(2):242–7.PubMedGoogle Scholar
  95. 95.
    Morange PE, Tregouet DA, Frere C, Saut N, Pellegrina L, Alessi MC, et al. Biological and genetic factors influencing plasma factor VIII levels in a healthy family population: results from the Stanislas cohort. Br J Haematol. 2005 Jan;128(1):91–9.PubMedGoogle Scholar
  96. 96.
    Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994 Nov 26;344(8935):1453–7.PubMedGoogle Scholar
  97. 97.
    van Hylckama Vlieg A, Rosendaal FR. Interaction between oral contraceptive use and coagulation factor levels in deep venous thrombosis. J Thromb Haemost. 2003 Oct;1(10):2186–90.PubMedGoogle Scholar
  98. 98.
    Martinelli I, De Stefano V, Taioli E, Paciaroni K, Rossi E, Mannucci PM. Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium. Thromb Haemost. 2002 May;87(5):791–5.PubMedGoogle Scholar
  99. 99.
    Herrington DM, Vittinghoff E, Howard TD, Major DA, Owen J, Reboussin DM, et al. Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Arterioscler, Thromb Vasc Biol. 2002 Jun 1;22(6):1012–7.Google Scholar
  100. 100.
    Rosendaal FR, Vessey M, Rumley A, Daly E, Woodward M, Helmerhorst FM, et al. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol. 2002 Mar;116(4):851–4.PubMedGoogle Scholar
  101. 101.
    Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. Estrogen plus progestin and risk of venous thrombosis. Jama. 2004 Oct 6;292(13):1573–80.PubMedGoogle Scholar
  102. 102.
    Lindahl TL, Lundahl TH, Nilsson L, Andersson CA. APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee – a prospective study. Thromb Haemost. 1999 Jan;81(1):18–21.PubMedGoogle Scholar
  103. 103.
    Salvati EA, Della Valle AG, Westrich GH, Rana AJ, Specht L, Weksler BB, et al. The John Charnley Award: heritable thrombophilia and development of thromboembolic disease after total hip arthroplasty. Clin Orthop Relat Res. 2005 Dec;441:40–55.PubMedGoogle Scholar
  104. 104.
    Wu O, Robertson L, Langhorne P, Twaddle S, Lowe GD, Clark P, et al. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost. 2005 Jul;94(1):17–25.PubMedGoogle Scholar
  105. 105.
    Libourel EJ, Bank I, Meinardi JR, Balje -Volkers CP, Hamulyak K, Middeldorp S, et al. Co-segregation of thrombophilic disorders in factor V Leiden carriers; the contributions of factor VIII, factor XI, thrombin activatable fibrinolysis inhibitor and lipoprotein(a) to the absolute risk of venous thromboembolism. Haematologica. 2002 Oct;87(10):1068–73.PubMedGoogle Scholar
  106. 106.
    Meinardi JR, Middeldorp S, de Kam PJ, Koopman MM, van Pampus EC, Hamulyak K, et al. Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis. Blood Coagul Fibrinolysis. 2001 Dec;12(8):713–20.PubMedGoogle Scholar
  107. 107.
    Ho WK, Hankey GJ, Quinlan DJ, Eikelboom JW. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006 Apr 10;166(7):729–36.PubMedGoogle Scholar
  108. 108.
    Marchiori A, Mosena L, Prins MH, Prandoni P. The risk of recurrent venous thromboembolism among heterozygous carriers of factor V Leiden or prothrombin G20210A mutation. A systematic review of prospective studies. Haematologica. 2007 Aug;92(8):1107–14.PubMedGoogle Scholar
  109. 109.
    De Stefano V, Martinelli I, Mannucci PM, Paciaroni K, Chiusolo P, Casorelli I, et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med. 1999 Sep 9;341(11):801–6.PubMedGoogle Scholar
  110. 110.
    Margaglione M, D'Andrea G, Colaizzo D, Cappucci G, del Popolo A, Brancaccio V, et al. Coexistence of factor V Leiden and Factor II A20210 mutations and recurrent venous thromboembolism. Thromb Haemost. 1999 Dec;82(6):1583–7.PubMedGoogle Scholar
  111. 111.
    Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006 Jan;119(1):60–8.PubMedGoogle Scholar
  112. 112.
    Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 2007 Nov 15;110(10):2339–46.PubMedGoogle Scholar
  113. 113.
    Leibson CL, Needleman J, Buerhaus P, Heit JA, Melton LJ, 3rd, Naessens JM, et al. Identifying in-hospital venous thromboembolism (VTE): a comparison of claims-based approaches with the Rochester Epidemiology Project VTE cohort. Med Care. 2008 Feb;46(2):127–32.Google Scholar
  114. 114.
    Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005 Feb;128(3):275–90.PubMedGoogle Scholar
  115. 115.
    Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006 Jun 1;107(11):4214–22.PubMedGoogle Scholar
  116. 116.
    Tefferi A, Elliott M. Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F. Semin Thromb Hemost. 2007 Jun;33(4):313–20.PubMedGoogle Scholar
  117. 117.
    Spivak JL, Barosi G, Tognoni G, Barbui T, Finazzi G, Marchioli R, et al. Chronic myeloproliferative disorders. Hematology Am Soc Hematol Educ Program. 2003:200–24.Google Scholar
  118. 118.
    Vannucchi AM, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia. 2008 May 22.Google Scholar
  119. 119.
    Patel RK, Lea NC, Heneghan MA, Westwood NB, Milojkovic D, Thanigaikumar M, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. 2006 Jun;130(7):2031–8.PubMedGoogle Scholar
  120. 120.
    Colaizzo D, Amitrano L, Iannaccone L, Vergura P, Cappucci F, Grandone E, et al. Gain-of-function gene mutations and venous thromboembolism: distinct roles in different clinical settings. J Med Genet. 2007 Jun;44(6):412–6.PubMedGoogle Scholar
  121. 121.
    Regina S, Herault O, D'Alteroche L, Binet C, Gruel Y. JAK2 V617F is specifically associated with idiopathic splanchnic vein thrombosis. J Thromb Haemost. 2007 Apr;5(4):859–61.PubMedGoogle Scholar
  122. 122.
    Pardanani A, Lasho TL, Hussein K, Schwager SM, Finke CM, Pruthi RK, et al. JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients. Mayo Clin Proc. 2008 Apr;83(4):457–9.Google Scholar
  123. 123.
    Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res. 2006;118(5):555–68.PubMedGoogle Scholar
  124. 124.
    Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008 Feb;22(2):414–23.PubMedGoogle Scholar
  125. 125.
    Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 2007 Jun 18;96(12):1788–95.PubMedGoogle Scholar
  126. 126.
    Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006 May 17;98(10):708–14.PubMedGoogle Scholar
  127. 127.
    Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer. 2005 Dec 15;104(12):2822–9.PubMedGoogle Scholar
  128. 128.
    Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989 Feb 23;320(8):479–84.PubMedGoogle Scholar
  129. 129.
    Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham DL, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997 Nov 19;89(22):1673–82.PubMedGoogle Scholar
  130. 130.
    Lee AY, Levine MN. The thrombophilic state induced by therapeutic agents in the cancer patient. Semin Thromb Hemost. 1999;25(2):137–45.PubMedGoogle Scholar
  131. 131.
    Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008 May 15;111(10):4902–7.PubMedGoogle Scholar
  132. 132.
    Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg. 2006 Jan;243(1):89–95.PubMedGoogle Scholar
  133. 133.
    Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med. 1999 Sep 9;341(11):793–800.PubMedGoogle Scholar
  134. 134.
    Verso M, Agnelli G. Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. J Clin Oncol. 2003 Oct 1;21(19):3665–75.PubMedGoogle Scholar
  135. 135.
    Munoz FJ, Mismetti P, Poggio R, Valle R, Barron M, Guil M, et al. Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry. Chest. 2008 Jan;133(1):143–8.PubMedGoogle Scholar
  136. 136.
    Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ, 3rd. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000 Mar 27;160(6):761–8.PubMedGoogle Scholar
  137. 137.
    Ku G, White RH, Chew HK, Harvey D, Zhou H, Wun T. Incidence of venous thromboembolism in patients with acute Leukemia. Blood. 2006;108(11):Abstract #1497.Google Scholar
  138. 138.
    Semrad TJ, O'Donnell R, Wun T, Chew H, Harvey D, Zhou H, et al. Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg. 2007 Apr;106(4):601–8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Hematology, Department of Internal MedicineCollege of Medicine, Mayo ClinicRochesterUSA
  2. 2.Dept of Hematology ResearchMayo ClinicRochesterUSA

Personalised recommendations