Antiphospholipid syndrome: pathogenesis and a window of treatment opportunities in the future

Eur J Clin Invest 2010; 40 (5): 451–464 Abstract Background Antiphospholipid syndrome (APS) is a systemic autoimmune vascular disease characterized by recurrent thrombotic episodes and/or obstetric complications. Management of this disease has been restricted mainly to anticoagulation; however, in recent years, significant advancement has been made in elucidating the pathophysiology of the disease including antiphospholipid antibody (aPL)‐induced activation of the platelets, endothelial cells, monocytes, complement and coagulation cascade. Stemming from these advances, potential targeted therapeutic approaches have been proposed. Materials and methods We utilized a computer‐assisted search of the literature (MEDLINE, National Library of Medicine, Bethesda, MD, USA) up until September 2009 using the keywords: antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti beta‐2 glycoprotein antibodies, complement system, tissue factor, p38 mitogen‐activated protein kinase (p38 MAPK), nuclear factor kappa B, toll‐like receptors, annexin, Rituximab, statins and tumour necrosis factor. Results Several study groups have separately demonstrated the importance of inflammatory mediators in the pathogenesis of APS. It was also established that tissue factor, MAPK, nuclear factors kappa B, and the complement system are integral to the disease process. Toll‐like receptors and annexin have as well been associated with the disease pathophysiology. Some study groups proposed new targeted therapeutic strategies some of which have shown promising results in preclinical studies. These include Rituximab, complement inhibition, anti‐cytokine therapy, p38 MAPK inhibitors, nuclear factor inhibitors and tissue factor inhibitors. Conclusion As more insight is being gained into the pathophysiology of APS, newer therapeutic strategies are being proposed that might lead to safer and more efficacious treatment modalities in the future.