Resistance to activated protein C caused by a factor V gene mutation

Curr Opin Hematol. 1995 Sep;2(5):358-64. doi: 10.1097/00062752-199502050-00006.


Each year, approximately one in 1000 individuals suffers from venous thromboembolism. The pathogenesis of the disease is multifactorial and a thrombotic event is the result of a combination of genetic and circumstantial risk factors. Until recently, genetic defects could only be identified in a minority of thrombosis patients. The discovery of inherited resistance to activated protein C as a risk factor for thrombosis changed the situation for the better. In Western countries, activated protein C resistance is found in 20% to 60% of patients with thrombosis. Activated protein C resistance is caused by a single point mutation in the Factor V gene, leading to replacement of Arg(R)506 in the activated protein C cleavage site of Factor V with a Gln(Q). As a result, the activated protein C-mediated cleavage and inhibition of mutated Factor V (FV:Q506) is impaired, which leads to increased thrombin generation, a hypercoagulable state, and a life-long increased risk of thrombosis.

Publication types

  • Review

MeSH terms

  • Aged
  • Anticoagulants / pharmacology*
  • Drug Resistance / genetics
  • Factor V / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Point Mutation*
  • Protein C / pharmacology*
  • Risk Factors
  • Thrombophlebitis / genetics*


  • Anticoagulants
  • Protein C
  • Factor V