title: Epidemiology and pathophysiology of cancer-associated thrombosis.
abstract: Venous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice.
authors.affiliation: Royal Gwent Hospital, Cardiff Road, Newport NP202UB, UK. simon.noble@gwent.wales.nhs.uk
authors.forename: S
authors.initials: S
authors.lastname: Noble
authors.forename: J
authors.initials: J
authors.lastname: Pasi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D006487:Hemostasis; D006801:Humans; D009369:Neoplasms / Q000150:complications* / Q000628:therapy; D011655:Pulmonary Embolism / Q000209:etiology; D012008:Recurrence; D012307:Risk Factors; D013629:Tamoxifen / Q000009:adverse effects; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology*
chemical_list: D020533:Angiogenesis Inhibitors; D013629:Tamoxifen
references.citation: JAMA. 2008 Nov 19;300(19):2277-85
references.pmid: 19017914
references.citation: N Engl J Med. 2004 May 27;350(22):2257-64
references.pmid: 15163775
references.citation: N Engl J Med. 2004 Jun 3;350(23):2335-42
references.pmid: 15175435
references.citation: Lancet Oncol. 2005 Jun;6(6):401-10
references.pmid: 15925818
references.citation: Blood. 2001 Jul 15;98(2):492-4
references.pmid: 11435324
references.citation: Medicine (Baltimore). 1999 Sep;78(5):285-91
references.pmid: 10499070
references.citation: Arch Intern Med. 1997 Jan 13;157(1):57-62
references.pmid: 8996041
references.citation: J Thromb Haemost. 2004 Dec;2(12):2107-14
references.pmid: 15613014
references.citation: J Clin Oncol. 2006 Jan 20;24(3):431-6
references.pmid: 16365178
references.citation: JAMA. 2005 Feb 9;293(6):715-22
references.pmid: 15701913
references.citation: Lancet. 2005 Jan 1-7;365(9453):60-2
references.pmid: 15639680
references.citation: J Clin Oncol. 2003 Oct 1;21(19):3665-75
references.pmid: 14512399
references.citation: Thromb Haemost. 1994 Oct;72(4):548-50
references.pmid: 7878630
references.citation: Am J Med. 2006 Jan;119(1):60-8
references.pmid: 16431186
references.citation: J Thromb Haemost. 2004 Oct;2(10):1760-5
references.pmid: 15456487
references.citation: Arch Intern Med. 2005 Aug 8-22;165(15):1782-7
references.pmid: 16087828
references.citation: J Clin Oncol. 1991 Feb;9(2):286-94
references.pmid: 1988575
references.citation: Haematologica. 1997 Jul-Aug;82(4):423-8
references.pmid: 9299855
references.citation: J Exp Med. 2006 Mar 20;203(3):493-5
references.pmid: 16533890
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):47-56
references.pmid: 15569823
references.citation: Oncologist. 2003;8(4):381-8
references.pmid: 12897335
references.citation: Semin Thromb Hemost. 2004 Feb;30(1):31-44
references.pmid: 15034796
references.citation: Blood Rev. 2001 Jun;15(2):61-7
references.pmid: 11409906
references.citation: Blood. 2001 Sep 1;98(5):1614-5
references.pmid: 11520815
references.citation: Biochemistry. 1985 Sep 24;24(20):5558-67
references.pmid: 3935163
references.citation: Ann Surg. 2006 Jan;243(1):89-95
references.pmid: 16371741
references.citation: Blood. 2002 Sep 15;100(6):2272-3
references.pmid: 12229885
references.citation: Cancer Lett. 1999 Nov 1;146(1):61-6
references.pmid: 10656610
references.citation: J Clin Oncol. 2006 Jan 20;24(3):484-90
references.pmid: 16421425
references.citation: Lancet. 1995 Oct 14;346(8981):1004-5
references.pmid: 7475548
references.citation: Semin Thromb Hemost. 2008 Mar;34(2):143-5
references.pmid: 18645918
references.citation: Blood. 2002 Nov 15;100(10):3484-8
references.pmid: 12393647
references.citation: J Immunol. 1995 Jul 15;155(2):867-76
references.pmid: 7608564
references.citation: BMJ. 2003 Sep 13;327(7415):597-8
references.pmid: 12969928
references.citation: J Natl Cancer Inst. 2006 May 17;98(10):708-14
references.pmid: 16705125
references.citation: Br J Cancer. 2004 Jul 5;91(1):92-5
references.pmid: 15226761
references.citation: Cancer Res. 1999 May 1;59(9):2244-50
references.pmid: 10232615
references.citation: J Clin Oncol. 2005 Apr 10;23(11):2574-6
references.pmid: 15795413