Activated protein C resistance due to a factor V mutation associated with familial ischemic stroke

J Neurosurg Sci. 1997 Dec;41(4):373-8.


Recent findings have indicated the association between activated protein C (APC)-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from transient ischaemic attacks or stroke. Therefore, we studied APC-resistance in 14 young adults belonging to three different families with a history of transient ischemic attacks (TIAs) and stroke. Nine out of fourteen subjects showed APC-resistance but no deficiencies in the anticoagulant proteins AT III, PC and PS. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. A rapid screening method to detect factor V R506Q (Leiden) mutation without sequencing or restriction enzyme digestion has been set-up after biochemical analyses. DNA analysis showed a guanine to adenine transition at nucleotide 1,691 in patients and their relatives with poor response to activated protein C detected by APTT tests. Of 14 investigated subjects and their family members, 5 were normals, 6 were heterozygotes and 3 were homozygotes for factor V mutation. The mutation, in heterozygous form, was also found in 1.3% of our normal population (n = 75). Our findings indicate a possible involvement of APC-resistance in the pathogenesis of arterial thrombosis in young adults.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Base Sequence
  • Blood Coagulation Tests
  • Brain Ischemia / blood
  • Brain Ischemia / genetics
  • Cerebrovascular Disorders / blood
  • Cerebrovascular Disorders / genetics*
  • Drug Resistance / genetics
  • Exons
  • Factor V / analysis*
  • Factor V / genetics*
  • Female
  • Genes, Dominant
  • Humans
  • Ischemic Attack, Transient / blood
  • Ischemic Attack, Transient / genetics*
  • Male
  • Middle Aged
  • Nuclear Family
  • Point Mutation*
  • Protein C / pharmacology*


  • Protein C
  • factor V Leiden
  • Factor V