SCIENTIFIC SUBCOMMITTEE SESSION
6 July 2007 Palexpo, Geneva, Switzerland
Lupus Anticoagulant/Phospholipid-Dependent Antibodies
Chair: V. Pengo (Italy)
Co-Chairs: P. de Groot (The Netherlands), M. Galli (Italy), T. Ortel (USA), J. Rand (USA), G. Reber (Switzerland), R. Roubey (USA), A. Tripodi (Italy)
Vittorio Pengo (Italy) opened the seesion reminding speakers to be concise and that their presentation will last 10min with 5min discussion. No discussion if the presentation lasts 15’.
He then started his presentation on the survey on Lupus Anticoagulant LAC diagnosis made by central evaluation of positive plasma samples. Main results were that a false positive diagnosis of LAC is significantly more frequent in older patients, in those first diagnosed with LAC, in those in whom LAC is mild or on oral anticoagulant treatment. Knowledge of these characteristic may help physician and clinical pathologist to suspect false positive LAC.
Armando Tripodi (Italy) proposed the preparation of reference material for LAC determination. The aim of the project was to prepare certified lyophilized plasmas with assigned potency and to develop a system of standardization/quantification based on the above certified plasmas.Phase I consists in preparation of candidate certified plasmas, in their certification with potency assignement and definition of the scheme. Phase II will be a field study to assess the value of the scheme.
Ian Jennings (UK) confirmed the need for reference material for the diagnosis of LAC and illustrated the strategy and progress on the production of a candidate International reference plasma panel.
KM Devreese (Belgium). LAC activity due to β 2 glycoprotein (β 2GPI) antibodies shows a high correlation with thrombotic events. Methods to discriminate between ß 2 GPI dependent LAC and LAC caused by antibodies to various phospholipid-binding proteins could be a promising tool in the diagnosis of APS.
Guido Reber (Switzerland) stressed the need for standardization of anticardiolipin (aCL) and anti b 2Glycoprotein I (a b 2GPI) at the level of companies.
Silvia Pierangeli (USA). Cut-off values in aCL and a b 2GPI were calculated in a huge number of patients and confirmed to be similar to those proposed by most companies.
Doruk Erkan (USA) reported on the real world experience with antiphospholipid antibody and how stable are thet results over time. aPL results remained stable for at least three quarters of subsequent tests, regardless of the laboratory performing the test; the small amount of variation that occurred did not appear to be caused by aspirin, warfarin, or hydroxychloroquine use.
Philip de Groot (The Netherlands). The risk of thrombosis among healthy persons who have antiphospholipid antibodies have to be established. Ideally, a prospective study in which healthy persons with incidentally found positive antiphospholipid antibodies are followed, should give the answer. The second best is large population based case-control studies that are now available and that can be used to establish the thrombotic risk in patients with antiphospholipid antibodies who had experienced a first arterial or venous thrombosis. These studies have now been performed and they showed that when only elevated levels of anticardiolipin antibodies are considered, anticardiolipin antibodies were not related to venous or arterial thrombosis in patients with a first event but without any sign of autoimmune disease. For a b 2GPI antibodies, not enough studies are available to draw a firm conclusion. There is evidence that lupus anticoagulant is an independent risk factor in patients without signs of autoimmunity.
Bas de Laat (The Netherlands) Through the years the validation of the anti-beta2GPI antibody ELISA has been proven to be a point of concern. In addition, several groups have shown that a conformational change in beta2GPI is needed before antiphospholipid antibodies are able bind beta2GPI. The different purification methods of beta2GPI result in beta2GPI preparations with different conformations which might explain a part of the variations in the anti-beta2GPI antibody ELISA. We and others have shown that the pathological antibodies are directed against domain I. By performing the ELISA with domain I, this change in conformation is not needed as domain I is already accessible for antibodies. This might be one of the reasons for its high correlation with thrombosis compared to regular anti-beta2GPI antibody ELISA’s. In addition, it has been shown that anti-domain I antibodies are better correlated with thrombosis even when beta2GPI is properly folded. In conclusion, the anti-domain I ELISA might be a better assay for the detection of pathogenic antiphospholipid antibodies than the anti-beta2GPI antibody ELISA.
Monica Galli (Italy). To assess the clinical significance of lupus anticoagulants (LA) and antiphospholipid antibodies (aPL) towards thrombosis and abortions, we measured them in 112 patients whose samples were available at enrolment in the WAPS study. When considered separately, IgG antiß2-glycoprotein I (aß2GPI) and prothrombin (aPT) antibodies were associated to anamnestic arterial and venous thrombosis, respectively, and those to annexin AV (aAnAV) with abortions. IgM antibodies to protein S and the lupus ratio of the dilute prothrombin time were associated with prospectivethrombosis. LA-positive patients who carried IgG aß2GPI and aAnAV antibodies were at risk for both anamnestic abortion and prospective thrombosis.
Ingrid Pabinger (Austria). We performed a study in 4.756 individuals, in whom anticardiolipin antibodies were determined, and evaluated their mortality during follow up. Anticardiolipin antibodies were associated with cancer mortality but not with vascular mortality. Therefore anticardiolipin antibodies are not predicitive to identify patients with high cardiovascular mortality.
Robert Roubey (USA). An update on the Antiphospholipid Syndrome Collaborative Registry (APSCORE). Collaborative studies on collected plasma are wellcome.
Waander van Heerde (The Nederlands). AnxA5 form 2D lattices on physiological cell membranes. Anti-β 2GP1 and β 2GP1 disturb only the 2D lattice formation. The prothrombotic tendency in patients with antiphospholipid syndrome may be explained by interference into 2D lattice formation of AnxA5.
Luis R Lopez (USA). aPLs, specially a b 2GP1 occur frequently in patients with chest pain-ACS and are associated with higher rates of vascular complications. The presence of oxLDL/ b 2GPI complexes are significantly associated with severity and poor outcome of coronary artery disease.
QUESTIONNAIRE PROPOSED TO 13 SPEAKERS