Figure 1

Schematic views of anti-phospholipid syndrome pathogenic mechanisms. (a) Vascular anti-phospholipid syndrome (APS). Anti-phospholipid antibodies (aPLs) may target different cell types and soluble coagulations factors. Pathogenic aPLs are beta₂ glycoprotein I (β₂GPI)-dependent and activate complement after an inflammatory stimulus (second hit). Additional variables may affect aPL pathogenicity, such as the ability of antibodies to modulate different cell signaling and to display diverse epitope specificity and reactivity with modified β₂GPI. (b) Obstetric APS. β₂GPI-dependent aPLs may target trophoblast and decidual cells. β₂GPI can be present at the uterine level even in non-pregnant animals and it binds to trophoblast cells (syncytiotrophoblasts). A second hit is not apparently required, and female hormones or the pregnancy itself may be the equivalent of the second hit described for the vascular manifestations. As in vascular APS, the ability of antibodies to modulate different cell signaling and to display diverse epitope specificity and reactivity with modified β₂GPI may be additional variables that can affect aPL pathogenicity. APC, activated protein C; C?S, Protein C/S; FII, Factor II; FIXa, Factor IXa, FVIIa, Factor VIIa; FXa, Factor Xa; PT, prothrombin; TF, tissue factor; tPA, tissue plasminogen factor.