Model for mechanisms of the “lupus anticoagulant effect” and the inhibition of annexin-V and acceleration of coagulation by antiphospholipid antibodies. (A) Anionic phospholipids (negative charges), when exposed on the apical surface of the cell membrane bilayer, serve as potent cofactors for the assembly of three different coagulation complexes: the tissue factor (TF)-VII_a complex, the IX_a-VIII_acomplex and the X_a-V_a complex, and thereby accelerating blood coagulation. The TF complexes yield either factor IX_a or factor X_a, the IX_a complex yields factor X_a, and the X_a formed from both of these reactions is the active enzyme in the prothrombinase complex, which yields factor II_a (thrombin), which in turn cleaves fibrinogen to form fibrin. (B) Annexin-V, in the absence of aPL antibodies, forms clusters, which bind with high affinity to the anionic phospholipid surface and shield the surface from the assembly of the phospholipid-dependent coagulation complexes, thereby inhibiting coagulation reactions. (C) In the absence of annexin-V, aPL antibodies can prolong the coagulation times, compared with control antibodies, by reducing the access of coagulation factors to anionic phospholipids. This may result in a “lupus anticoagulation effect.” (D) In the presence of annexin-V, antiphospholipid antibodies, either directly or via interaction with protein-phospholipid cofactors, disrupt the ability of annexin-V to cluster on the phospholipid surface, resulting in a net increase of the amount of anionic phospholipid available for promoting coagulation reactions. This manifests in the net acceleration of coagulation in vitro and in thrombophilia in vivo.