Coexistence of hereditary homocystinuria and factor V Leiden--effect on thrombosis

N Engl J Med. 1996 Mar 21;334(12):763-8. doi: 10.1056/NEJM199603213341204.


Background: Venous and arterial thromboembolism occurs in only about one third of patients homozygous for homocystinuria, which suggests that other, contributory factors are necessary for the development of thrombosis in these patients. Factor V Leiden, an R506Q mutation in the gene coding for factor V, is the most common cause of familial thrombosis and could be a potentiating factor.

Methods: We determined activated partial-thromboplastin times in the presence and absence of activated protein C and tested for the factor V Leiden mutation in 45 members of seven unrelated consanguineous kindreds in which at least 1 member was homozygous for homocystinuria.

Result: Thrombosis (venous, arterial, or both) occurred in 6 of 11 patients with homocystinuria (age, 0.2 to 8 years). All six also had the factor V Leiden mutation. One patient with prenatally diagnosed homocystinuria who was also heterozygous for factor V Leiden has received warfarin therapy since birth and has not had thrombosis (age, 18 months). Of four patients with homocystinuria who did not have factor V Leiden, none had thrombosis (ages at this writing, 1 to 17 years). Three women who were heterozygous for both homocystinuria and factor V Leiden had recurrent fetal loss and placental infarctions.

Conclusions: Patients with concurrent homocystinuria and factor V Leiden can have an increased risk of thrombosis. Screening for factor V Leiden may be indicated in patient with homocystinuria and their family members.

MeSH terms

  • Adolescent
  • Base Sequence
  • Blood Coagulation Disorders / complications
  • Blood Coagulation Disorders / genetics
  • Child
  • Child, Preschool
  • Factor V / genetics*
  • Female
  • Homocystinuria / complications*
  • Homocystinuria / genetics
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation*
  • Protein C / genetics
  • Protein C / metabolism
  • Risk Factors
  • Thrombosis / etiology
  • Thrombosis / genetics*


  • Protein C
  • Factor V