D. Dizontownson et al., THE FACTOR-V LEIDEN MUTATION WHICH PREDISPOSES TO THROMBOSIS IS NOT COMMON IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME, Thrombosis and haemostasis, 74(4), 1995, pp. 1029-1031
Antiphospholipid syndrome is associated with venous, arterial, and pla
cental thrombosis, possibly through autoantibody impairment of phospho
lipid-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 m
utation, causes an amino acid substitution of glutamine for arginine a
t position 506 in the factor V molecule and renders the protein resist
ant to proteolytic inactivation by activated protein C and thus predis
poses to thrombosis (2, 3). We hypothesized that some individuals with
antiphospholipid syndrome may also carry the Leiden mutation, and thu
s have a ''second hit'' predisposition to thrombosis. To test this hyp
othesis, allele-specific hybridization and allele-specific restriction
analysis were used to test for the Leiden mutation in thirty women wi
th the antiphospholipid syndrome, 10 of whom had a history of thrombos
is. None of the women were heterozygous or homozygous for the factor V
mutation. We conclude that the presence of the factor V Leiden mutati
on is not a prerequisite for the thrombotic events in patients with an
tiphospholipid syndrome, due to the occurrence of thrombosis seen in p
atients lacking the factor V mutation.