The
antiphospholipid syndrome (APS) is a thrombotic disorder leading to
spontaneous abortions,
venous thromboses,
myocardial infarctions and
strokes. Although the syndrome is associated with characteristic
autoantibodies, these tests have poor predictive value for
thrombosis. The aim of the study was to determine whether the combined presence of two types of
antiphospholipid antibodies can be associated with a high-risk subset of
thrombosis-prone patients. One hundred and thirty-four sera from a lupus clinic were tested for
antibodies to
beta2-glycoprotein I (beta2GPI),
protein S and
prothrombin. In a group of 29 patients for whom plasma was available, free (functional)
protein S levels were also measured.
Autoantibodies to beta2GPI and
protein S are associated with each other. Dual reactivity to beta2GPI and
protein S correlates with increased history of thrombotic events (69% of doubly reactive patients) when compared to either type of
autoantibody alone (37% of patients with only anti-beta2GPI and 38% with only anti-
protein S, P=0.04 and P=0.01, respectively) or neither reactivity (37%). Among 29 patients tested for free (functional,
anticoagulant)
protein S levels, the lowest levels were found in patients with
antibodies to beta2GPI and/or
protein S, and all four patients with a history of
thrombosis had below-normal free
protein S levels. These associations were not found with antiprothrombin
antibodies. In conclusion dual
autoantibodies to beta2GPI and
protein S are associated with increased history of
thrombosis in the
antiphospholipid syndrome.