THE FACTOR-V LEIDEN MUTATION WHICH PREDISPOSES TO THROMBOSIS IS NOT COMMON IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

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.