Les difficultés diagnostiques des lupus anticoagulants

Specific and sensitive assays of lupus anticoagulant (LA) are of particular importance because persistent LA positivity (and/or anticardiolipin) in patients with a history of thrombosis or recurrent fetal loss is a major risk factor for recurrence leading to appropriate therapy, especially anticoagulant therapy. LA are heterogeneous autoantibodies that are measured by means of their capacity to prolong phospholipids-dependent clotting assays. This heterogeneity has 2 major consequences: 1/there is no gold standard plasma control against which assays, cutoff values and reagents could be evaluated 2/ for a given LA the results of the clotting times of the different assays and interpretations are variable. That let to create over the years numerous assays and diagnostic algorithms to express the results. Finally the laboratory diagnosis of LA remains difficult and the accuracy of LA testing is far from safe. After an optimal pre-analytical step, including the scrupulous preparation of a plasma without platelet, the biological diagnosis of LA includes four steps: 1/screening with at least 2 highly sensitive assays 2/ demonstration of an inhibitory activity by plasma mixing studies 3/ demonstration that the inhibitor is phospholipid-dependent 4/ Exclusion of an other coagulopathy especially a coagulation factor deficiency or an anti-factor antibody. It is now possible to carry out an integrated test comprising screening, plasma mixing step and confirmation. Two measures have been proposed to improve the diagnosis of LA 1/ the use, as positive control specimens, of plasmas spiked with monoclonal antibodies against human beta 2 glycoprotein 1 and prothrombin because the autoantibodies that cause LA activity are predominantly directed against there two proteins. 2/ the expression of the results as normalised ratio.