Conformation of beta2glycoprotein I and its effect on coagulation

beta 2glycoprotein I (beta 2GPI) is the major antigen in the antiphospholipid syndrome. It has been shown that beta 2GPI can adapt to different conformations, a circular, a S-shaped and a J-shaped conformation. In literature anticoagulant properties of beta 2GPI have been indicated, though there is no consensus on how beta 2GPI exerts a certain action. This article will first review existing data on the conformation of beta 2GPI. In addition, we will investigate whether the conformation of beta 2GPI plays a role in in the proposed anticoagulant activity of beta 2GPI. We investigated the effect of native beta 2GPI and phospholipid-bound beta 2GPI on thrombin generation (TG). Native beta 2GPI was found to have no significant effect on the TG regardless of the concentration of tissue factor. On the contrary, beta 2GPI preincubated with phospholipids significantly inhibited TG triggered with low TF concentration, suggesting an effect on the intrinsic pathway. This indicates that native beta 2GPI in circulation obtains its anticoagulant activity in the presence of anionic phospholipids such as activated blood cells thereby serving as an inhibitory modulator in hemostasis.