Les anticorps antiphospholipides : mécanismes d'action et implications cliniques

[Antiphospholipid antibodies mechanisms of action and clinical implications] Two groups of antiphospholipid antibodies (aPLA) have been described, the lupus anticoagulant (LAC) and the anticardiolipin antibodies (aCA). The LAC is binding a platelet phospholipid preventing the interaction on the platelet membrane of calcium and factors Xa and V which are the components of the prothrombin converting principle. The LAC is therefore anticoagulant in vitro, but in vivo it behaves like a procoagulant. The aCA were used initially to diagnose syphilis, but are positive in numerous conditions not related to syphilis. They enhance blood coagulation in vivo, like the LAC. Both antibodies are closely related but not identical. The aPLA are present in at least one third of patients with systemic lupus erythematosus (SLE), often with an 'atypical' form of SLE, even without antinuclear or DNA-binding antibodies. Other conditions where LAC and aCA are found, less commonly, are various autoimmune diseases, both systemic or organ-specific, infections, malignant neoplasms and even in 2 to 75% of normal subjects. Various drugs may induce their presence. The tissular target of these antibodies remains controversial, platelets, endothelial cells, thrombomodulin being the main candidates. The presence of a blood cofactor, beta 2-glycoprotein I, is necessary for the binding of the antibody to the phospholipids, and it might be the true antigen. The major clinical symptoms related to aPLA are thrombocytopeina, thrombosis both venous and arterial, and recurrent fetal loss. Central nervous system involvement consists mainly of transient ischemic attacks, but many other neurologic conditions may be present, always related to arterial thrombosis. An association between fetal loss and the presence of aPLA is shown in most studies, but the true incidence is still debatable. A statistically significant relationship exists only in women with SLE or lupus-like disease, with a high titer of aPLA, and a history of previous fetal loss. The best treatment for the anticardiolipin syndrome is not established and controlled clinical trials are currently in progress. Prophylactic therapy in asymptomatic patients with aPLA is not advocated. Warfarin, heparin, aspirin, ticlopidine are the usual treatment in patients with thrombosis. Long term anticoagulation is required for serious thrombotic events. For recurrent pregnancy loss, inhibitors of platelet aggregation like aspirin and dipyridamole may be beneficial, with or without prednisolone. Plasmapheresis, high doses of corticosteroids and immunosuppressive therapy may be of some use in severe cases of recurrent thromboses.