THE ANTIPHOSPHOLIPID SYNDROME AND PREGNANCY

During the last decade a new clinical syndrome, the antiphospholipid s yndrome, was described. This syndrome, which gradually developed over many years, is now defined as the association of so-called antiphospho lipid antibodies with arterial or venous thrombosis, recurrent fetal l oss, thrombocytopenia, or neurologic disorders. Antiphospholipid antib odies, namely lupus anticoagulants and anticardiolipin antibodies, are closely related phospholipid-binding autoantibodies which are, respec tively, measured via their capacity to prolong phospholipid-dependent coagulation assays or via their capability to bind to cardiolipin, a n egatively charged phospholipid, immobilized on a microtiter plate. Ant iphospholipid antibodies are found in about one third of patients with systemic lupus erythematosus (SLE) or related autoimmune disorders, a nd their presence concurs with an increased risk for the above-mention ed clinical features. About half of the patients with an antiphospholi pid syndrome do not fulfill the criteria for SLE or ''lupus-like'' dis orders and are diagnosed as having a ''primary antiphospholipid syndro me.'' Thrombosis probably is the common denominator of the major clini cal symptoms observed in this syndrome. Virtually all arterial or veno us sites may be involved. In pregnancy, vascular disturbances of the u teroplacental circulation can lead to recurrent fetal losses and sever e forms of preeclampsia. The possible pathogenicity of antiphospholipi d antibodies has been extensively studied. A causal relationship betwe en these antibodies and thrombosis or fetal loss has been proposed via interference with several natural phospholipid-dependent antithrombot ic pathways such as prostacyclin release, the protein C/protein S path way, contact mediated fibrinolysis, etc. None of the mechanisms sugges ted to explain hypercoagulability has received general acceptance. Rec ent animal in vivo experiments, however, provide direct evidence for a pathogenic role of antiphospholipid antibodies. An experimental antip hospholipid syndrome could be induced in naive mice upon active or pas sive immunization with anticardiolipin antibodies. How to explain the pathogenicity of antiphospholipid antibodies remains an open question, The characterization of the precise antigenic determinants against wh ich antiphospholipid antibodies are directed should help to clarify th is. In this regard, important progress has been made. Anticardiolipin antibodies were found not to be directed against cardiolipin itself bu t against the complex that insolubilized cardiolipin forms with beta-2 -glycoprotein I, a plasma protein with anticoagulant properties. Furth ermore, some lupus anticoagulants were found to be directed against th e complex formed by human prothrombin and negatively charged phospholi pid rather than against phospholipid itself. Antiphospholipid antibodi es binding to other protein/phospholipid complexes such as protein C-p hospholipid and protein S-phospholipid have meanwhile been found. Trea tment of patients with the antiphospholipid syndrome remains mainly em pirical because of lack of large controlled trials. However, there is growing consensus for thr use of intensive anticoagulation to prevent thrombosis and fetal loss in patients with a manifest antiphospholipid syndrome.