Thrombosis and Cancer

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Thrombosis and Cancer

• Mario DICATO, Garry MAHON
• Hematology-Oncology
• Centre Hospitalier
• L-1210 Luxembourg
• dicato.mario_at_chl.lu garry.mahon_at_cec.eu.int

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ESTIMATED PREVALENCE OF VENOUS THROMBOEMBOLISM
DURING THE COURSE OF COMMON TYPES OF CANCER (Ann.
Rev. Med. 1999)
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CANCER TREATMENS AS RISK FACTORS FOR VTE IN
CANCER PATIENTS
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• TF, CP

VIIA Xa
TNF-IL-1
TF
VIIa
Tumor cells
monocytes endothelial cells
thrombin
Platelet aggregation
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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...

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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

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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)

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ACQUIRED

• ANTIPHOSPHOLIPID Ab
• CANCER
• PNH
• MYELOPROLIFERATIVE SYNDROMES
• NEPHROTIC SYNDROMES
• CHEMOTHERAPY

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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 1998abstr.

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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)

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MUTATIONS V LEIDEN, MTHFR AND PT IN CANCER
PATIENTS WITH VENOUS THROMBO-EMBOLIC DISORDERS.
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The Thrombophilic mutations V Leiden, PT and
MTHFR are in Hardy-Weinberg equilibrium
(ASH 2001, M.D. et al. abstr. 3985)
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PATIENTS

• Cancer VTE 54
• Cancer - VTE 53

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FREQUENCY OF MUTATIONS
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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)