INHIBITION OF PROTHROMBIN ACTIVATION BY ANTIPHOSPHOLIPID ANTIBODIES AND BETA(2)-GLYCOPROTEIN-1

Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal pla sma protein beta(2)-glycoprotein 1 (beta(2)GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta(2)GP1. Using a purified system for m easurement of prothrombin activation to thrombin, we demonstrated sign ificant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta(2)GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by e quivalent concentrations of patient IgG correlated well with the exten t of prolongation of the plasma dotting time in lupus anticoagulant as says of whole patient plasma. Additional studies with eight patient Ig G preparations indicated that the addition of beta(2)GP1 to patient Ig G-phospholipid vesicle mixtures resulted in either independently addit ive inhibition by the two protein species (six cases) or potential inh ibition of beta(2)GP1 of the IgG inhibitory activity demonstrable in t he absence of beta(2)GP1 (two cases). In addition, beta(2)GP1-independ ent inhibition of prothrombin activation also occurred with three pati ent IgG preparations obtained by affinity binding to cardiolipin.