Factor V Leiden

Summary

Factor V Leiden is an inherited autosomal dominant condition that increases the risk of forming large life-threatening blood clots. This disorder is caused by a point mutation in factor V at position 506, which changes an amino acid residue from arginine to glutamine. As a result, the mutated factor V becomes resistant to degradation by proteins C and S. This disease is particularly common in caucasians, and usually presents with recurrent venous blood clots, such as deep venous thrombosis or pulmonary embolism. Miscarriage is another finding seen in women with factor V Leiden. Patients with Factor V Leiden are usually treated with anticoagulants.

Key Points

• Factor V Leiden
  • Pathogenesis
    • Hypercoagulable state/thrombophilia from mutated factor V
      • Mutated Factor V is resistant to degradation by activated protein C
  • Genetics
    • Point mutation causes amino acid swap from Arginine to Glutamine at amino acid position 506 (Arg506Gln)
      • Caused by DNA Guanine to Adenine swap at nucleotide position 1691 (G1691A)
    • Autosomal dominant inheritance
      • May exhibit a familial pattern of inheritance
    • More common in Caucasians
      • 1-9% are heterozygous carriers
    • Most common cause of inherited hypercoagulable state
  • Presentation
    • Recurrent blood clots
      • DVT
      • PE
      • Cerebral vein thrombosis
    • Miscarriage in pregnancy
      • Recurrent pregnancy loss
  • Diagnosis
    • Activated protein C resistance assay (factor V Leiden specific functional assay)
      • if positive, confirm with DNA testing
    • Normal PT & PTT
      • No changes in laboratory measurements of intrinsic or extrinsic coagulation pathways
    • Normal bleeding time
      • No changes in platelet plug formation
  • Treatment
    • Anticoagulants
      • As needed for thrombotic episodes
      • LMWH bridge to warfarin
    • Avoid external causes of hypercoagulability
      • OCPs
      • hormone replacement therapy