Lupus Anticoagulant/Phospholipid-Dependent Antibodies
DRAFT Subcommittee Minutes
23 July 2011
9:00-13:00
Room Sakura
Chairman: Thomas L Ortel (US)
Co-Chairmen: Tatsuya Atsumi (JP), Ph de Groot (NL), Bas de Laat (NL), Vittorio Pengo (IT), Jacob Rand (US), Guido Reber (CH), Armando Tripodi (IT)
The subcommittee meeting opened after the Educational Session with three primary areas for Discussion during the session.
Lupus Anticoagulant Testing. The first set of presentations discussed issues related to the Subcommittee Communication published in 2009 updating the recommendations for lupus anticoagulant testing (Pengo V, et al., J Thromb Haemost, 2009; 7: 1737-1740). Dr. Ian Jennings reported on compliance in the United Kingdom with the 2009 Guidelines by using a questionnaire to the UK NEQAS participants and a proficiency testing exercise circulated six months after the guidelines were published. They found several areas on non-compliance, including issues related to pre-analytical (citrate concentration; double-spinning plasma); analytical (test selection and determination of cut-off values); and post-test (lack of test interpretation) stages. Proficiency testing found excellent accuracy for LA negative and strongly positive plasma samples, limitations with “weakly” positive samples.
Dr. Piet Miejer followed Dr. Jennings with a presentation on compliance with the Guidelines based on data collected from the ECAT surveys. He found that laboratory diagnostic accuracy did not appear to improve with an increasing number of tests for lupus anticoagulants being performed. He also noted considerable heterogeneity in the results obtained from mixing studies. He also presented data on the problems that clinical laboratories have with ‘borderline’ results, with poor correlation for consistently obtaining the same result when testing the same plasma sample (up to 15% of laboratories resulted a sample as negative on one analysis, yet positive on a second analysis!). The question this raised is whether there might be problems related to the definition of the cutoff values for negative vs. positive results.
Dr. Katrien Devreese presented the last talk in this section, reviewing her data on the importance of mixing studies in the diagnosis of lupus anticoagulants. In particular, the issue was whether integrated tests, which do not include a mixing step, are acceptable. She found that the mixing study was actually quite important to include, even with an integrated sample, to help distinguish samples with factor deficiencies from samples with a lupus anticoagulant.
Anticardiolipin and Anti-b2-glycoprotein I Antibody Standards. These discussions were in follow-up to presentations at last year’s meeting in Cairo, with a primary focus on developing appropriate standards and calibrators to improve diagnostic results obtained by the ELISA-based assays for phospholipid-dependent antibodies.
Dr. Silvia Pierangeli summarized final results from the 13th International Congress on Antiphospholipid Antibodies, which was held in last year in Galveston, TX. The wet workshop at this conference compared polyclonal and monoclonal standards from several different sources, using antiphospholipid antibody-positive and negative serum samples, and found limitations with the monoclonal preparations. Dr. Bas de Laat followed Dr. Pierangeli, updating the subcommittee on ongoing efforts to develop anti-?2glycoprotein I domain 1-specific monoclonal antibodies that could be used as potential tools for standardizing anti-?2-glycoprotein I ELISA results. Critical issues included conformation of the immobilized ?2-glycoprotein I. Dr. de Laat proposed a project that would compare as many assays/standards as possible against multiple patient samples (recruited and collected from multiple investigators) to assess individual assays, standards, and calibrators.
Diagnostic Strategies for APS. The last session focused on developing a clinical and laboratory-based strategy to improve the diagnosis of APS. Dr. Kotaro Otomo from Hokkaido University presented the Antiphospholipid Score, which combines the results from anticardiolipin, anti-?2-glycoprotein I, anti-prothrombin/PS antibodies, and lupus anticoagulant testing into a ‘score’ to assess the likelihood that an individual patient has APS.
Plans for 2011-12.
Follow-up: Continue to assess impact of the 2009 Guidelines for Lupus Anticoagulant testing.
Subcommittee Communication: Plan to prepare a manuscript for submission on performance of anticardiolipin and anti-?2-glycoprotein I antibody ELISA-based assays, including discussion of patient selection, pre-analytical variables, analytical variables, and post-testing issues, including interpretive analyses.
Project in development: analysis of ELISA-based assays to determine best strategies for test performance.
