Targeting of the annexin A5 anticoagulant shield may be a significant mechanism for thrombosis and pregnancy losses in APS. This may occur via high affinity antibodies that recognize phospholipid-binding proteins that are capable of interfering with the assembly of the annexin A5 shield on phospholipid surfaces or via direct recognition of annexin A5 by autoantibodies. In addition, antibodies against other members of the annexin family of proteins may also have pathogenic roles in APS. It is anticipated that further research will elucidate the biologic functions of these proteins and their roles in the aPL disease processes.