The Antiphospholipid Syndrome and Pregnancy: Invited Review

Abstract

During the last decade a new clinical syndrome, the antiphospholipid syndrome, was described. This syndrome, which gradually developed over many years, is now defined as the association of so-called antiphospholipid antibodies with arterial or venous thrombosis, recurrent fetal loss, thrombocytopenia, or neurologic disorders. Antiphospholipid antibodies, namely lupus anticoagulants and anticardiolipin antibodies, are closely related phospholipid-binding autoantibodies which are, respectively, measured via their capacity to prolong phospholipid-dependent coagulation assays or via their capability to bind to cardiolipin, a negatively charged phospholipid, immobilized on a microtiter plate. Antiphospholipid antibodies are found in about one third of patients with systemic lupus erythematosus (SLE) or related autoimmune disorders, and their presence concurs with an increased risk for the above-mentioned clinical features. About half of the patients with an antiphospholipid syndrome do not fulfill the criteria for SLE or “lupus-like” disorders and are diagnosed as having a “primary antiphospholipid syndrome.” Thrombosis probably is the common denominator of the major clinical symptoms observed in this syndrome. Virtually all arterial or venous sites may be involved. In pregnancy, vascular disturbances of the uteroplacental circulation can lead to recurrent fetal losses and severe forms of preeclampsia. The possible pathogenicity of antiphospholipid antibodies has been extensively studied. A causal relationship between these antibodies and thrombosis or fetal loss has been proposed via interference with several natural phospholipid-dependent antithrombotic pathways such as prostacyclin release, the protein C/protein S pathway, contact mediated fibrinolysis, etc. None of the mechanisms suggested to explain hypercoagulability has received general acceptance. Recent animal in vivo experiments, however, provide direct evidence for a pathogenic role of antiphospholipid antibodies. An experimental antiphospholipid syndrome could be induced in naive mice upon active or passive immunization with anticardiolipin antibodies. How to explain the pathogenicity of antiphospholipid antibodies remains an open question. The characterization of the precise antigenic determinants against which antiphospholipid antibodies are directed should help to clarify this. In this regard, important progress has been made. Anticardiolipin antibodies were found not to be directed against cardio-lipin itself but against the complex that insolubilized cardiolipin forms with β-2-glycoprotein I, a plasma protein with anticoagulant properties. Furthermore, some lupus anticoagulants were found to be directed against the complex formed by human prothrombin and negatively charged phospholipid rather than against phospholipid itself. Antiphospholipid antibodies binding to other protein/phospholipid complexes such as protein C-phospholipid and protein S-phospholipid have meanwhile been found. Treatment of patients with the antiphospholipid syndrome remains mainly empirical because of lack of large controlled trials. However, there is growing consensus for the use of intensive anticoagulation to prevent thrombosis and fetal loss in patients with a manifest antiphospholipid syndrome.

Key Words:

• Abortion
• Anticardiolipin antibodies
• Antiphospholipid antibodies
• Antiphospholipid syndrome
• Aspirin
• Corticosteroids
• Heparin
• Immunoglobulins
• Lupus anticoagulant
• Preeclampsia
• Pregnancy
• Thrombosis