The antiphospholipid syndrome. Pathogenesis, molecular basis and clinical aspects

Background: In 1983 the antiphospholipid syndrome was first described as an independent clinical entity by Graham Hughes and characterized by thrombos is, thrombocytopenia and recurrent fetal losses. In the following years evi dence accumulated from various studies that the thrombotic events in the an tiphospholipid syndrome correlate with elevated serum titers of antiphospho lipid antibodies. These autoantibodies represent a very heterogeneous group as multiple specificities against various negatively charged phospholipids are found. Most commonly described are antibodies against cardiolipin, but also cross-reactivities between the different phospholipids art: observed. Moreover, efficient binding of antiphospholipid antibodies against a phosp holipid requires the presence of certain protein-cofactors which on the oth er hand can be antigens themselves. Pathogenesis: Although numerous animal models strongly indicate that antiph ospholipid antibodies play a causal role in the pathogenesis of the disease , the exact pathogenetic mechanisms are still to be elucidated. There is ac cumulating evidence from in vitro studies with poly- and monoclonal antipho spholipid antibodies that these autoantibodies are able to interfere with a ll aspects of the hemostatic balance. Influences of antiphospholipid antibo dies on plasmatic processes of the coagulation cascade as well as antithrom botic and fibrinolytic mechanisms are described. Furthermore, antiphospholi pid antibodies are able to exert prothrombotic effects on cells participati ng in hemostasis, mainly platelets and endothelial cells. Therapeutic Approaches: Therapeutic approaches to the antiphospholipid synd rome today are mainly restricted to the prevention of further thrombosis by permanent anticoagulation. Although 30-50% of all patients, according to t he literature, with moderately to highly elevated antiphospholipid antibody titers develop the clinical symptoms of the syndrome, there are only few s tudies investigating the benefits of a prophylactic anticoagulation of the affected patients. There is an urgent need for prospective clinical studies to clarify this question. Therapy of nonthrombotic manifestations of the a ntiphospholipid syndrome are scarcely standardized. In obstetrics, treatmen t with aspirin, heparin and steroids is the main approach. Here also contro lled studies are restricted to small numbers of patients and are therefore of limited validity.