β₂-Glycoprotein I Modulates the Anticoagulant Activity of Activated Protein C on the Phospholipid Surface

Summary

The objective of this study was to determine whether (β₂-glycoprotein I (β₂GPI) has procoagulant activity by inhibiting the anticoagulant activity of activated protein C (APC). β₂GPI inhibited significantly the APC-catalyzed inactivation of factor Va in an assay using factor V-deficient plasma and physiological levels of protein S and factor Va. This inhibitory effect was diminished by the addition of increasing concentrations of phospholipids, suggesting that β₂GPI competitively inhibits the binding of APC to the phospholipid surface. β₂GPI inhibited weakly factor Va- and phospholipid-dependent prothrombinase activity at concentrations similar to those to inhibit APC activity. The depletion of β₂GPI from plasma led to only a slight shortening of the diluted Russell’s viper venom-dependent clotting time, but to a strong and significant potentiation of the anticoagulant activity of APC. These results suggest that under certain physiological conditions β₂GPI has procoagulant property by inhibiting the phospholipid-dependent APC anticoagulant activity.

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