ANTIPHOSPHOLIPID ANTIBODIES ACCELERATE PLASMA COAGULATION BY INHIBITING ANNEXIN-V BINDING TO PHOSPHOLIPIDS - A LUPUS PROCOAGULANT PHENOMENON

The antiphospholipid syndrome is a thrombophilic condition marked by a ntibodies that recognize anionic phospholipid-protein cofactor complex es. We recently reported that exposure to IgG fractions from antiphosp holipid patients reduces the level of annexin-V, a phospholipid-bindin g anticoagulant protein, on cultured trophoblasts and endothelial cell s and accelerates coagulation of plasma exposed to these cells. Theref ore, we asked whether antiphospholipid antibodies might directly reduc e annexin-V binding to noncellular phospholipid substrates. Using elli psometry, we found that antiphospholipid IgGs reduce the quantity of a nnexin-V bound to phospholipid bilayers; this reduction is dependent o n the presence of beta(2)-glycoprotein 1. Also, exposure to plasmas co ntaining antiphospholipid antibodies reduces annexin-V binding to phos phatidyl serine-coated microtiter plates, frozen thawed washed platele ts, activated partial thromboplastin time (aPTT) reagent and prothromb in time reagent and reduces the anticoagulant effect of the protein. T hese studies show that antiphospholipid antibodies interfere with the binding of annexin-V to anionic phospholipid and with its anticoagulan t activity. This acceleration of coagulation, due to reduced binding o f annexin V, stands in marked contrast to the ''lupus anticoagulant ef fect'' previously described in these patients. These results are the f irst direct demonstration of the displacement of annexin-V and the con sequent acceleration of coagulation on noncellular phospholipid surfac es by antiphospholipid antibodies. (C) 1998 by The American Society of Hematology.