Thrombosis and Cancer Mario DICATO, Garry MAHON

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Thrombosis and Cancer Mario DICATO, Garry MAHON

  1. 1. Thrombosis and Cancer Mario DICATO, Garry MAHON Hematology-Oncology Centre Hospitalier L-1210 Luxembourg dicato.mario@chl.lu garry.mahon@cec.eu.int
  2. 2. ESTIMATED PREVALENCE OF VENOUS THROMBOEMBOLISM DURING THE COURSE OF COMMON TYPES OF CANCER (Ann. Rev. Med. 1999) CANCER SITEPREVALENCE (%)All malignancies10-15 Ø Pancreas28 Ø Lun Ø Ø Ø Ø Ø Ø
  3. 3. CANCER TREATMENS AS RISK FACTORS FOR VTE IN CANCER PATIENTS RISK FACTORPATIENTS WITH TVE (%)Immobilisation14Cancer surgery
  4. 4. TF, CP VIIA Xa Tumor cells TNF-IL-1 TF VIIa monocytes endothelial cells thrombin Platelet aggregation
  5. 5. VENOUS THROMBOPHILIA HEREDITARY: Prevalence • AT III ~ 0,2 % • Protein C , S ~ 0,2 % • VArg 506 (Leiden) 3 - 8 % • Hyperhomocysteinemia (+ arterial, folic acid), MTHFR 40% (35-60) • PT 0-2% • ? Plasminogen, Dysfibrinogenemia...
  6. 6. V Leiden • Prevalence – Heterozygotes (Caucasians) 5 % – Patient Cohorts DVT 20 - 60 % – DVT - Pregnancy 60 % – DVT - Oral Birth Control Meds 34 % • ! Multiple Genetic Deficits • Long term studies : – heterozygotes ? • Ø arterial thrombosis
  7. 7. V LEIDEN, OESTROGENS AND DVT VL OESTROGENS DVT (per 10.000 y) - - 0,8 - + 3 + - 5,7 + + 28,5 HOMOZYGOSITY > 100 (BMJ 1996, 313 : 1127)
  8. 8. ACQUIRED • ANTIPHOSPHOLIPID Ab • CANCER • PNH • MYELOPROLIFERATIVE SYNDROMES • NEPHROTIC SYNDROMES • CHEMOTHERAPY
  9. 9. V LEIDEN • Normal population controls : 240 • Heterozygotes 18 • Homozygotes 0 ⇒ Allele frequency 3,75 % • Essential thrombocytemia : 41 • Heterozygotes 3 • Homozygotes 0 ⇒ Allele frequency 3,65 % M. Dicato et al.: ASH 1998:abstr.
  10. 10. ESSENTIAL THROMBOCYTHEMIA • n = 41 V Leiden allele frequency 3,65 % • PT & MTHFR (0 & 40%) • n = 30 15 TED 8 BLEEDING 10 no hemostatic problem (M.Dicato et al.: ASH 1999, abstr.1119)
  11. 11. MUTATIONS V LEIDEN, MTHFR AND PT IN CANCER PATIENTS WITH VENOUS THROMBO-EMBOLIC DISORDERS.
  12. 12. The Thrombophilic mutations V Leiden, PT and MTHFR are in Hardy-Weinberg equilibrium (ASH 2001, M.D. et al. abstr. 3985)
  13. 13. PATIENTS • Cancer + VTE 54 • Cancer - VTE 53
  14. 14. FREQUENCY OF MUTATIONS V LEIDENMTHFRPTCANCER + VTE13271CANCER – VTE4415p V
  15. 15. CONCLUSION • In cancer patients with VTE, testing for mutations is only useful if there is a previous personal or family history of VTE (M. Dicato et al. : ASH 2001, Abstr. 3984)

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