Summary
Antiphospholipid syndrome is associated with venous, arterial, and placental thrombosis,
possibly through autoantibody impairment of phospholipid-dependent protein C activation.
Recently, a missense mutation in the factor V gene (1691 G → A) has been identified
that results in an abnormal factor V product (1). This mutation, known as the Leiden
mutation, causes an amino acid substitution of glutamine for arginine at position
506 in the factor V molecule and renders the protein resistant to proteolytic inactivation
by activated protein C and thus predisposes to thrombosis (2, 3). We hypothesized
that some individuals with antiphospholipid syndrome may also carry the Leiden mutation,
and thus have a “second hit” predisposition to thrombosis. To test this hypothesis,
allele-specific hybridization and allele-specific restriction analysis were used to
test for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10
of whom had a history of thrombosis. None of the women were heterozygous or homozygous
for the factor V mutation. We conclude that the presence of the factor V Leiden mutation
is not a prerequisite for the thrombotic events in patients with antiphospholipid
syndrome, due to the occurrence of thrombosis seen in patients lacking the factor
V mutation.
