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

migratory thrombophlebitis associated with an occult visceral malignancy

Trousseau’s Syndrome

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

The annual incidence in Taiwan is much lower than in Western populations

【 Thromb Haemost 2012; 108: 225–235】

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】

【 Blood 2007 110: 1723-1729】

1

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)】

【 Blood 2007 110: 1723-1729】

2

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)

Selectin ligand

Phosphatidylserinenegatively-charged phospholipids

【 Blood. 2013;122(11):1873-1880】

【 Blood 2007 110: 1723-1729】

3

Cysteine Proteinase

directly activated factor X in the absence of factor VII

【 Blood 2007 110: 1723-1729】

4

Tumor Hypoxia

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

【 Blood 2007 110: 1723-1729】

5

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

【 J Thromb Haemost 2007; 5: 632–4.】

12

2

【 Cochrane Database Syst Rev. 2012 Feb 5;2】

Symptomatic VTE for LMWH vs placebo

NNT = 60

【 Cochrane Database Syst Rev. 2012 Feb 5;2】

Major bleeding for LMWH vs placebo

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

soluble P-selectinD-dimer

【 Blood 2008 112: 2703-2708】

Vienna Cancer and Thrombosis Study (CATS)

Risk Assessment Models

Score VTE in 6 months

0 0%

3 10.3%

>=5 35%

【 Blood 2013 122: 2011-2018】

Risk Assessment Modelsin 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