ANTICARDIOLIPIN ANTIBODIES BLOCK THE INHIBITION BY BETA-2-GLYCOPROTEIN-I OF THE FACTOR-XA GENERATING ACTIVITY OF PLATELETS

Antiphospholipid antibodies, defined either by lupus anticoagulant (LA ) activity or positive anticardiolipin immunoabsorbent assay (ACA) are associated with a predisposition to thromboses, recurrent fetal loss or thrombocytopenia. The mechanisms for these predispositions remain u ndefined. We have enriched immunoglobulin fractions from two patient p lasmas to obtain antibodies with LA activity but no ACA, or conversely , with ACA positivity but no LA, in order to investigate in vitro char acteristics which might explain a thrombotic propensity. beta2-glycopr otein I (beta2-GPI), the plasma cofactor required for ACA binding to n egatively charged phospholipid, has previously been shown to inhibit p rothrombinase generation in the presence of activated platelets (8). W e now report that beta2-GPI, at physiological concentrations, inhibits the generation of factor Xa in the presence of activated gel-filtered platelets. Further, ACA interferes with this inhibition, resulting in protracted, unopposed factor Xa generation. This interference with be ta2-GPI, a natural anticoagulant component of plasma, is potentially p rothrombotic. LA immunoglobulins behave differently and inhibit factor Xa generation in a manner similar to beta2-GPI. These findings provid e the basis for a previously unsuspected mechanism for thrombosis in p atients with aPL.