Despite the experimental research data on antiphospholipid syndrome (APS), the pathogenesis of thrombosis and fetal loss remains unknown. The objective of this study was to analyze the major advances in the field of complement activation as a possible thrombosis mechanism in the APS.
The authors conducted a systemic analysis of the English literature and summarized both animal and human data that indicate the inappropriate complement activation as a mechanism causing thrombosis in the APS.
The important role of complement activation in the pathogenesis of fetal loss was established using mice deficient in a complement regulatory protein. Further studies have shown that the infusion of human IgG antiphospholipid antibodies (aPL) induced fetal loss in pregnant mice, an effect that was abrogated by the concurrent administration of a C3 convertase inhibitor. Further studies suggested that C5a and neutrophils were the key components responsible for fetal injury. Moreover, use of F(ab)'2 fragments of aPL suggested the complement activation occurred mainly via the classical pathway. Other studies using models of induced thrombosis suggested that antibodies against β2GPI required the presence of terminal complement components to induce thrombus formation, and mice deficient in C3 or C5 were found to be resistant to aPL-induced thrombosis. Based on the aforementioned findings, it has been suggested that heparin prevents fetal loss in patients with APS by inhibiting complement activation rather than by its anticoagulant effect.
The studies on complement are significant because they shift the focus of research in APS from thrombosis to inflammation. However, as human data are limited, more clinical research is necessary before the above findings translate in changes in the management of APS.