Cancerassociated Thrombotic Disease Reporter CR Supervisor VS Cancerassociated
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
Outline � History � Epidemiology � Pathogenesis � Thromboprophylaxis
Outline � History � Epidemiology � Pathogenesis � Thromboprophylaxis
Cancer-associated Thrombosis The first report was published by the French physician Jean-Baptiste Bouillaud in 1823
Cancer-associated Thrombosis Widely quoted description by Armand Trousseau in 1865 Trousseau’s Syndrome migratory thrombophlebitis associated with an occult visceral malignancy
Outline � History � Epidemiology � Pathogenesis � Thromboprophylaxis
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】
Type of Cancer VS. Risk of VTE 【Blood 2013 122: 1712 -1723】
Later stage of cancer, higher risk of VTE 【Blood 2013 122: 1712 -1723】
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 � 【Thromb Haemost 2012; 108: 225– 235】
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 � 【Thromb Haemost 2012; 108: 225– 235】 【Blood 2013 122: 1712 -1723】
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 � 【Thromb Haemost 2012; 108: 225– 235】 � The annual incidence in Taiwan is much lower than in Western populations
Cancer with VTE in Taiwan 【Thromb Haemost 2012; 108: 225– 235】
Cancer with VTE in Taiwan 【Thromb Haemost 2012; 108: 225– 235】
Outline � History � Epidemiology � Pathogenesis � Thromboprophylaxis
Pathogenesis � Mucin � Tissue Factor � Tumor Hypoxia � Cysteine Proteinase � Oncogene Activation
【Blood 2007 110: 1723 -1729】
1 【Blood 2007 110: 1723 -1729】
Mucin � Trousseau’s syndrome associated with mucin-producing carcinomas � Glycosylated secretory products of epithelial cells � ligands for the selectins
Selectin (P-selectin and L-selectin) 【J. Clin. Invest. 112: 853– 862 (2003) 】
2 【Blood 2007 110: 1723 -1729】
Tissue Factor (TF) � TF-rich tumor surface and TF-positive, Tumor-derived microparticle � Correlation between elevated TF and VTE
TF-positive, Tumor-derived Microparticle (TMP) Phosphatidylserine negatively-charged phospholipids Selectin ligand 【Blood. 2013; 122(11): 1873 -1880 】
3 【Blood 2007 110: 1723 -1729】
Cysteine Proteinase � directly activated factor X in the absence of factor VII
4 【Blood 2007 110: 1723 -1729】
Tumor Hypoxia � increase the expression of genes that facilitate coagulation, including tissue factor and plasminogen activator inhibitor type 1 (PAI-1)
5 【Blood 2007 110: 1723 -1729】
Oncogene Activation � MET oncogene involve up-regulation of PAI-1 and cyclooxygenase-2 (COX-2) genes
【Blood 2007 110: 1723 -1729】
Outline � History � Epidemiology � Pathogenesis � Thromboprophylaxis
The increasing incidence of VTE 【Blood 2013 122: 1712 -1723】
VTE increase mortality prospective follow-up of >26000 subjects Tromsø study, prospective follow-up of >26000 subjects 【Blood 2013 122: 1712 -1723】
VTE related cancer mortality 1 2 2 【J Thromb Haemost 2007; 5: 632– 4. 】
Symptomatic VTE for LMWH vs placebo NNT = 60 【Cochrane Database Syst Rev. 2012 Feb 5; 2】
Major bleeding for LMWH vs placebo 【Cochrane Database Syst Rev. 2012 Feb 5; 2】
Risk Assessment Models Risk score VTE in 2. 5 months Low 0 0. 3% Intermediate 1 -2 2% High >=3 6. 7% negative predictive value of 98. 5% at the cutoff point for high risk (>=3) 【Blood 2013 122: 2011 -2018】
D-dimer and P-selectin Vienna Cancer and Thrombosis Study (CATS) D-dimer soluble P-selectin 【Blood 2008 112: 2703 -2708】
Risk Assessment Models Score VTE in 6 months 0 0% 3 10. 3% >=5 35% 【Blood 2013 122: 2011 -2018】
Risk Assessment Models in Taiwan population 【Thromb Haemost 2012; 108: 225– 235】
Prophylaxis or Not
? Prophylaxis or Not
? Prophylaxis or Not
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
Thanks for your attention
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