MECHANISM AND EFFECTS OF THE BINDING OF LUPUS ANTICOAGULANT IGG AND PROTHROMBIN TO SURFACE PHOSPHOLIPID

We report here experiments on how lupus anticoagulant antibodies (LA I gG) that react with prothrombin bind to surface phospholipid and affec t prothrombin's affinity for surface phospholipid and activation to th rombin. LA IgG was purified by protein A chromatography from the plasm a of 16 patients of whom four had associated hypoprothrombinemia and 1 0 had experienced thrombosis. Many LA IgG bound, in the absence of pho spholipid and calcium. not only to immobilized prothrombin but to both prethrombin 1 and fragment 1, which established at least an oligoclon al origin of LA IgG. No LA IgG bound to thrombin. Although prothrombin and Ca2+ were required to support binding of LA IgG to immobilized ph osphatidylserine (PS). prothrombin at higher concentrations inhibited binding, presumably by competing with prothrombin/LA IgG complexes for PS binding sites. Prethrombin 1, which cannot bind to PS, also inhibi ted binding of many LA IgG to PS, presumably by forming competing solu ble prethrombin 1/LA IgG complexes. Despite their ability to react wit h prothrombin independent of phospholipid, LA IgG enhanced binding of prothrombin to immobilized phospholipid and to cultured human umbilica l vein endothelial cells. Prothrombin bound with LA IgG to the surface of endothelial cell monolayers could be activated to thrombin after s upernatant prothrombin and LA IgG were washed away. The relation is di scussed of these observations to a hypothesis that LA IgG mediated con centration of prothrombin on cell surface phospholipid represents a me chanism by which LA IgG could increase thrombotic risk. (C) 1996 by Th e American Society of Hematology.