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Cancer-associated Thrombotic Disease

Reporter: CR 吳嘉芸 Supervisor: VS 邱宗傑. Cancer-associated Thrombotic Disease. Reporter: CR 吳嘉芸 Supervisor: VS 邱宗傑. Cancer-associated Thrombotic Disease. Outline. History Epidemiology Pathogenesis Thromboprophylaxis. Outline. History Epidemiology Pathogenesis Thromboprophylaxis.

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Cancer-associated Thrombotic Disease

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  1. Reporter: CR 吳嘉芸 Supervisor: VS 邱宗傑 Cancer-associated Thrombotic Disease

  2. Reporter: CR 吳嘉芸 Supervisor: VS 邱宗傑 Cancer-associated Thrombotic Disease

  3. Outline • History • Epidemiology • Pathogenesis • Thromboprophylaxis

  4. Outline • History • Epidemiology • Pathogenesis • Thromboprophylaxis

  5. Cancer-associated Thrombosis The first report was published by the French physician Jean-BaptisteBouillaud in 1823

  6. Cancer-associated Thrombosis Widely quoted description by Armand Trousseau in 1865 Trousseau’s Syndrome migratory thrombophlebitis associated with an occult visceral malignancy

  7. Outline • History • Epidemiology • Pathogenesis • Thromboprophylaxis

  8. Epidemiology • About 20% - 30% of venous thromboembolism (VTE)are cancer- associated • Cancer patients have a 4 to 7-fold increased risk of VTE compared with the general population 【Blood 2013 122: 1712-1723】

  9. Type of Cancer VS. Risk of VTE 【Blood 2013 122: 1712-1723】

  10. Later stage of cancer, higher risk of VTE 【Blood 2013 122: 1712-1723】

  11. Cancer with VTE in Taiwan • 497,180 cancer patients, between 1997 to 2005, with a median follow-up of 21.3 months • Incidence: 185 events per 100,000 person-years • 11.5 times higher than the general population 【ThrombHaemost 2012; 108: 225–235】

  12. Cancer with VTE in Taiwan • 497,180 cancer patients, between 1997 to 2005, with a median follow-up of 21.3 months • Incidence: 185 events per 100,000 person-years • 11.5 times higher than the general population 【ThrombHaemost 2012; 108: 225–235】 【Blood 2013 122: 1712-1723】

  13. Cancer with VTE in Taiwan • 497,180 cancer patients, between 1997 to 2005, with a median follow-up of 21.3 months • Incidence: 185 events per 100,000 person-years • 11.5 times higher than the general population • The annual incidence in Taiwan is much lower than in Western populations 【ThrombHaemost 2012; 108: 225–235】

  14. Cancer with VTE in Taiwan 【ThrombHaemost 2012; 108: 225–235】

  15. Cancer with VTE in Taiwan 【ThrombHaemost 2012; 108: 225–235】

  16. Outline • History • Epidemiology • Pathogenesis • Thromboprophylaxis

  17. Pathogenesis • Mucin • Tissue Factor • Tumor Hypoxia • Cysteine Proteinase • Oncogene Activation

  18. 【Blood 2007 110: 1723-1729】

  19. 1 【Blood 2007 110: 1723-1729】

  20. Mucin • Trousseau’s syndrome associated with mucin-producing carcinomas • Glycosylated secretory products of epithelial cells • ligands for the selectins

  21. Selectin (P-selectin and L-selectin) 【J. Clin. Invest. 112:853–862 (2003)】

  22. 2 【Blood 2007 110: 1723-1729】

  23. Tissue Factor (TF) • TF-rich tumor surface and TF-positive, Tumor-derived microparticle • Correlation between elevated TF and VTE

  24. TF-positive, Tumor-derived Microparticle (TMP) Phosphatidylserine negatively-charged phospholipids Selectinligand 【Blood. 2013;122(11):1873-1880】

  25. 3 【Blood 2007 110: 1723-1729】

  26. Cysteine Proteinase • directly activated factor X in the absence of factor VII

  27. 4 【Blood 2007 110: 1723-1729】

  28. Tumor Hypoxia • increase the expression of genes that facilitate coagulation, including tissue factor and plasminogen activator inhibitor type 1 (PAI-1)

  29. 5 【Blood 2007 110: 1723-1729】

  30. Oncogene Activation • MET oncogene involve up-regulation of PAI-1 and cyclooxygenase-2 (COX-2) genes

  31. 【Blood 2007 110: 1723-1729】

  32. Outline • History • Epidemiology • Pathogenesis • Thromboprophylaxis

  33. The increasing incidence of VTE 【Blood 2013 122: 1712-1723】

  34. VTE increase mortality prospective follow-up of >26000 subjects Tromsø study, prospective follow-up of >26000 subjects 【Blood 2013 122: 1712-1723】

  35. VTE related cancer mortality 1 2 2 【J ThrombHaemost 2007; 5: 632–4.】

  36. Symptomatic VTE for LMWH vs placebo NNT = 60 【Cochrane Database Syst Rev. 2012 Feb 5;2】

  37. Major bleeding for LMWH vsplacebo 【Cochrane Database Syst Rev. 2012 Feb 5;2】

  38. Risk Assessment Models negative predictive value of 98.5%at the cutoff point for high risk (>=3) 【Blood 2013 122: 2011-2018】

  39. D-dimer and P-selectin Vienna Cancer and Thrombosis Study (CATS) D-dimer soluble P-selectin 【Blood 2008 112: 2703-2708】

  40. Risk Assessment Models 【Blood 2013 122: 2011-2018】

  41. Risk Assessment Modelsin Taiwan population 【ThrombHaemost 2012; 108: 225–235】

  42. Prophylaxis or Not

  43. ？ Prophylaxis or Not

  44. ？ Prophylaxis or Not

  45. Conclusions • Cancer increased risk of VTE, especially advanced stage • The pathogenesis included mucin, tissue factor, and others • VTE increased mortality • Thromboprophylaxis is an issue, especially in high risk group

  46. Thanks for your attention

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