FACTOR V LEIDEN

• Biochemical aspects:
  • Dahlback described an inherited disorder associated with hypercoagulation (1993). This disorder is due to a mutation in Factor V gene (the mutated gene is called Factor V Leiden). Mutation at nucleotide 1691: Guanine-> Adenine, causing substitution at position 506: Arginine-> Glycine.
  • Protein C is thought to be activated in vivo by thrombin after the latter has formed a complex with a cofactor (thrombomodulin) on the surfaces of endothelial cells. Protein C inactivates the activated cofactors Va and VIIIa. The substitution of amino acid at position 506 on Factor V Leiden prevents this inactivation leading to hypercoagulation. This is known as activated protein C (APC) resistance.
• Pathological Basis:
  • Two forms of Factor V Leiden exist: (a) Heterozygous: 3-7% of general population, 3-5 fold increase in risk of deep vein thrombosis, 20% have thrombosis by 33 y/o; (b) Homozygous: 0.06-0.25% of general population, 50-100 fold increase in risk of deep vein thrombosis, 40% have thrombosis by 33 y/o.
  • Some patients do not have thrombosis unless exposed to hemostatic challenge.
  • Increased risk for hypercoagulation in combination with Protein C or S deficiency.
  • Factor V procoagulant activity is normal.
• Treatment:
  • Treatment for acute episode: heparin.
  • Long term treatment: coumadin.