Procoagulant effect of anti-β2-glycoprotein I antibodies with lupus anticoagulant activity

Prothrombin time (PT) is routinely used to monitor oral anticoagulant treatment in patients with the antiphospholipid antibody syndrome (APS). The fact that PT is a phospho-lipid (PL)-dependent coagulation test raises the possibility that lupus anticoagulant (LA) might interfere with this test, thus complicating the control of anticoagulant treatment. The effect of 6 affinity-purified preparations of anti- (a)beta 2-glycoprotein 1 (GP1) antibodies with LA activity an the PT was tested. Instead of prolonging PT as expected, the a beta 2-GP1 antibodies reduced the PT of both normal plasma and anticoagulated plasma by a mean of 2.4 seconds and 5.6 seconds, respectively. This effect was also observed using other 5 commercially available preparations of thromboplastin. The a beta 2-GP1-mediated reduction in PT was dose-dependent and was lost upon removal of beta 2-GP1. The failure of a beta 2-GP1 antibodies to express LA activity in PT was found to depend on the fact that calcium ions were added together with PL at the beginning of the assay. In fact, modification of the standard diluted Russell Viper venom time (dRVVT) test by adding calcium ions together with PL resulted in a loss of a beta 2-GP1 anticoagulant activity. The procoagulant effect was not as evident in an assay that used stimulated monocytes as a source of thromboplastin. These results show that a beta 2-GP1 antibodies exhibit an 'in vitro' procoagulant effect in PT and an anticoagulant effect in dRVVT only when the interaction with their antigen and PL occurs in the absence of calcium ions. (C) 1999 by The American Society of Hematology.