Pathogenesis and management of antiphospholipid syndrome.
Antiphospholipid antibodies are a heterogeneous group of autoantibodies that have clear associations with thrombosis and pregnancy morbidity, and which together constitute the 'antiphospholipid syndrome' (APS). However, the pathophysiology of these complications is not well understood and their heterogeneity suggests that more than one pathogenic process may be involved. Diagnosis remains a combination of laboratory analysis and clinical observation but there have been significant advances in identifying specific pathogenic features, such as domain I-specific anti-β2-glycoprotein-I antibodies. This in turn has pointed to endothelial and complement activation as important factors in the pathogenesis of APS. Consequently, although anticoagulation remains the standard treatment for thrombotic APS and during pregnancy, the realisation that these additional pathways are involved in the pathogenesis of APS has significant implications for treatment: agents acting outside the coagulation system, such as hydroxychloroquine for pregnancy complications and sirolimus as an inhibitor of the mammalian target of rapamycin (mTOR) pathway, are now under evaluation and represent a radical change in thinking for haematologists. Conventional anticoagulation is also under challenge from new, direct acting anticoagulants. This review will provide a comprehensive overview of the evolving understanding of APS pathogenesis and how this and novel therapeutics will alter diagnosis and management.
Department of Haematology, Imperial College Healthcare NHS Trust and Imperial College London, Hammersmith Hospital, London, UK.
Deepa R J
DRJ
Arachchillage
Department of Haematology, Imperial College Healthcare NHS Trust and Imperial College London, Hammersmith Hospital, London, UK.
Mike
M
Laffan
D000925:Anticoagulants / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000209:etiology*; D001323:Autoantibodies / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005544:Forecasting; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000209:etiology; D000069283:Rituximab / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology
D000925:Anticoagulants; D001323:Autoantibodies; D003169:Complement Inactivator Proteins; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D053482:beta 2-Glycoprotein I; D000069283:Rituximab; D006886:Hydroxychloroquine; D020123:Sirolimus
antiphospholipid antibodies; complement; immunosuppression; pregnancy complications; thrombosis; warfarin