First, an overview of pathophysiology of phospholipid-dependent antibodies was presented by Dr. DA Triplett. He pointed out the heterogeneity of these antibodies, which differ in terms of antigenic targets, methods of detection, and, possibly, clinical correlations. The various mechanisms potentially predisposing to thrombosis were also analyzed and discussed.

The second session dealt with the problems that still exist in the detection of the different phospholipid-dependent antibodies.

Dr. S. Machin updated the clinical validation of new tests.

Dr. M. Taylor reported on the final results of the ISLA-5, an international survey which involved 29 laboratories from 12 different countries. Seven plasmas were provided in limited aliquots and each laboratory was asked to identify the presence or absence of lupus anticoagulants using the coagulation tests commonly carried out in daily practice. A good degree of inter-laboratory concordance was observed, less in the two cases with "weak" lupus anticoagulants.

Dr. J. Arnout reported the functional characterization of murine monoclonal antibodies directed against human prothrombin which behave as lupus anticoagulants in "in vitro" coagulation tests. LA screening tests performed on plasmas spiked with these monoclonals, variably mixed with LA-positive monoclonal antibodies against human Beta-2-glycoprotein I, showed that both types of LA antibodies prolong clotting in an additive way.

Plasma spiked with these antibodies have the potential to serve as reference materials to compare the sensitivity and responsiveness of the different tests proposed for the detection of lupus anticoagulants.

The NCCLS document on anticardiolipin assay was presented by Dr. J.T. Brandt.

Dr. A. Tincani, on behalf of the European forum, reported the results of two surveys that analyzed the standardization of the ELISA methodology to detect anticardiolipin and the antib 2-glycoprotein I antibodies. Twenty-four and 19 centers participated in the two studies, respectively. A reasonable degree of concordance was observed for IgG but not IgM anticardiolipin antibody measurement. Regarding the antib 2-glycoprotein I antibodies measurement, the use of a common cut off point appeared to improve the agreement among centers.

The prevalence and clinical correlations with thrombosis of antibodies directed against Factor XII were presented by Dr. W. Jones.

The third session dealt with clinical trials. Dr. A. Tripodi reported the final results of an international collaborative study on the monitoring of oral anticoagulation of lupus anticoagulant-positive patients. The main conclusion was that the PT-INR measured with the majority of the thromboplastins is not affected by the presence of lupus anticoagulants, provided that the reagents were calibrated against the same international standard on the same instrument.

Dr. R. Brey first gave an overview of the treatment of neurologic complications of the antiphospholipid syndrome. Next, she updated the results of clinical trials on stroke.

Three different trials are currently being conducted to establish the best primary and secondary prophylaxis of arterial and venous thrombosis in patients with antiphospholipid antibodies. Dr. G. Finazzi reported the ad-interim analysis of the WAPS study, a prospective, randomized clinical trial aimed at assessing the risk/benefit ratio of high-dose oral anticoagulation in patients with antiphospholipid antibodies and thrombosis.

Dr. M. Crowther described the PAPRE trial, a double-blind study that randomizes patients with antiphospholipid antibodies and one (arterial or venous) thrombotic event to receive warfarin targeted at a PT INR either of 20-2.9 or 3.0-4.0.

Dr. L. Mitchell described the PRECLUDE study, a randomized, placebo-controlled trial, aimed at assessing the efficacy of warfarin in the primary prevention of thrombosis in SLE patients with antiphospholipid antibodies.

Finally, Dr. T. Barbui summarized the activities of the last three years, pointing out the role of the Subcommittee in the development of clinical trials in patients with the antiphospholipid syndrome.

A booklet with the short reports of the presentations is available upon request to Dr.Barbui.