N Engl J Med 1996, 334(12): 763-768
Mandel,Hanna; Brenner,Benjamin; Berant,Moshe; Rosenberg,Nurith; Lanir,Naomi; Jakobs,Cornelis; Fowler,Brian; Seligsohn,Uri
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.
Results: 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 patients with
homocystinuria and their family members.