A Consensus Approach to the Formulation of Guidelines for Laboratory Testing and Reporting of Antiphospholipid Antibody Assays

ABSTRACT

Despite numerous past and ongoing efforts, there remains significant variation in results from assays for the major antiphospholipid antibodies (aPL), namely anticardiolipin (aCL), anti-β2 glycoprotein I (anti-β2GPI), and lupus anticoagulant (LA). There is therefore a need to produce comprehensive guidelines on laboratory testing and reporting of aPL assays. However, because of the paucity of good-quality published evidence, there is a heavy reliance on expert opinion, and thus the existing consensus guidelines for aPL testing and reporting are largely eminence based rather than evidence based. This may potentially bias recommendations to reflect the personal preferences of those who have the greatest influence during the guideline formulation process. This article largely details the experience of the Australasian Anticardiolipin Working Party in undertaking a consensus approach to formulation of guidelines on aCL and anti-β2GPI testing and reporting, including measures taken to minimize these issues. Despite the time-consuming nature of the process, given the paucity of good-quality published evidence, formulation of guidelines by the consensus process remains an important initiative to improve the standardization of aPL testing and reporting.

Anti-β2 glycoprotein I antibodies - anticardiolipin antibodies - antiphospholipid antibodies - anti-β2GPI - aCL - aPL - antiphospholipid syndrome - APS - consensus - guidelines - standardization

REFERENCES

• 1 Miyakis S, Lockshin M D, Atsumi T et al.. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).  J Thromb Haemost. 2006;  4 295-306
• 2 Wong R C, Favaloro E J. Clinical features, diagnosis and management of the antiphospholipid syndrome.  Semin Thromb Hemost. 2008;  34 295-304
• 3 Harris E N, Pierangeli S S. Primary, secondary and catastrophic antiphospholipid syndrome: what's in a name?.  Semin Thromb Hemost. 2008;  34 219-226
• 4 Pierangeli S S, Harris E N. A quarter of a century in anticardiolipin antibody testing and attempted standardization has led us to here, which is?.  Semin Thromb Hemost. 2008;  34 313-328
• 5 Reber G, Boehlen F, de Moerloose P. Technical aspects in laboratory testing for antiphospholipid antibodies: is standardisation an impossible dream?.  Semin Thromb Hemost. 2008;  34 340-346
• 6 Andreoli L, Rizzini S, Allegri S, Meroni P, Tincani A. Are the current attempts at standardisation of antiphospholipid antibodies still useful? Emerging technologies signal a shift in direction.  Semin Thromb Hemost. 2008;  34 356-360
• 7 Wong R CW, Gillis D, Adelstein S et al.. Consensus guidelines on anti-cardiolipin antibody testing and reporting.  Pathology. 2004;  36 63-68
• 8 Triplett D A. Antiphospholipid antibodies.  Arch Pathol Lab Med. 2002;  126 1424-1429
• 9 Greaves M, Cohen H, MacHin S J, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome.  Br J Haematol. 2000;  109 704-715
• 10 Tincani A, Allegri F, Balestrieri G et al.. Minimal requirements for antiphospholipid antibodies ELISAs proposed by the European Forum on antiphospholipid antibodies.  Thromb Res. 2004;  114 553-558
• 11 Tincani A, Allegri F, Sanmarco M et al.. Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determinations—a cooperative project of the European Antiphospholipid Forum.  Thromb Haemost. 2001;  86 575-583
• 12 Reber G, de Moerloose P. Anti-beta2-glycoprotein I antibodies—when and how should they be measured?.  Thromb Res. 2004;  114 527-531
• 13 Wong R C, Favaloro E J, Adelstein S et al.. Consensus guidelines on anti-beta 2 glycoprotein I testing and reporting.  Pathology. 2008;  40 58-63
• 14 Wong R C, Adelstein S, Gillis D, Favaloro E J. Development of consensus guidelines for anticardiolipin and lupus anticoagulant testing.  Semin Thromb Hemost. 2005;  31 39-48
• 15 de Groot P G, Derksen R H, de Laat B. Twenty-two years of failure to set up undisputed assays to detect patients with the antiphospholipid syndrome.  Semin Thromb Hemost. 2008;  34 347-355
• 16 Tripodi A. Laboratory testing for lupus anticoagulants: diagnostic criteria and use of screening, mixing, and confirmatory studies.  Semin Thromb Hemost. 2008;  34 373-379
• 17 Ledford-Kraemer M R. Laboratory testing for lupus anticoagulants: preexamination variables, mixing studies, and diagnostic criteria.  Semin Thromb Hemost. 2008;  34 380-388
• 18 Favaloro E J, Wong R CW, Silvestrini R et al.. A multi-laboratory peer-assessment quality assurance program based evaluation of anti-cardiolipin and beta-2-glycoprotein-1 antibody assays.  Semin Thromb Hemost. 2005;  31 73-84
• 19 Favaloro E J, Silvestrini R. Assessing the usefulness of anticardiolipin antibody assays: a cautious approach is suggested by high variation and limited consensus in multilaboratory testing.  Am J Clin Pathol. 2002;  118 548-557
• 20 Pengo V, Biasiolo A, Bison E et al.. Antiphospholipid antibody ELISAs: survey on the performance of clinical laboratories assessed by using lyophilized affinity-purified IgG with anticardiolipin and anti-beta2-glycoprotein I activity.  Thromb Res. 2007;  120 127-133
• 21 Favaloro E J, Wong R C, Jovanovich S, Roberts-Thomson P. A review of beta2 -glycoprotein-l antibody testing results from a peer-driven multilaboratory quality assurance program.  Am J Clin Pathol. 2007;  127 441-448
• 22 Tripodi A, Biasiolo A, Chantarangkul V, Pengo V. Lupus anticoagulant (LA) testing: performance of clinical laboratories assessed by a national survey using lyophilized affinity-purified immunoglobulin with LA activity.  Clin Chem. 2003;  49 1608-1614
• 23 Arnout J, Meijer P, Vermylen J. Lupus anticoagulant testing in Europe: an analysis of results from the first European Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta2-glycoprotein I.  Thromb Haemost. 1999;  81 929-934
• 24 Favaloro E J, Bonar R, Sioufi J et al.. Multi-laboratory testing of thrombophilia: current and past practice in Australasia as assessed through the RCPA Haematology QAP.  Semin Thromb Hemost. 2005;  31 49-58
• 25 Jennings I, Greaves M, Mackie I J et al.. Lupus anticoagulant testing: improvements in performance in a UK NEQAS proficiency testing exercise after dissemination of national guidelines on laboratory methods.  Br J Haematol. 2002;  119 364-369
• 26 Jennings I, Kitchen S, Woods T A, Preston F E, Greaves M. Potentially clinically important inaccuracies in testing for the lupus anticoagulant: an analysis of results from three surveys of the UK National External Quality Assessment Scheme (NEQAS) for Blood Coagulation.  Thromb Haemost. 1997;  77 934-937
• 27 Roussi J, Roisin J P, Goguel A. Lupus anticoagulants: first French interlaboratory Etalonorme survey.  Am J Clin Pathol. 1996;  105 788-793
• 28 Reber G, Arvieux J, Comby E et al.. Multicenter evaluation of nine commercial kits for the quantitation of anticardiolipin antibodies. The Working Group on Methodologies in Haemostasis from the GEHT (Groupe d'Etudes sur l'Hemostase et la Thrombose).  Thromb Haemost. 1995;  73 444-452
• 29 Wong R CW, Favaloro E J, Pollock W et al.. A multi-centre evaluation of the intra-assay and inter-assay variation of commercial and in-house anti-cardiolipin antibody assays.  Pathology. 2004;  36 182-192
• 30 Reber G, Schousboe I, Tincani A et al.. Inter-laboratory variability of anti-beta2-glycoprotein I measurement. A collaborative study in the frame of the European Forum on Antiphospholipid Antibodies Standardization Group.  Thromb Haemost. 2002;  88 66-73
• 31 Wong R CW, Wilson R J, Pollock W, Steele R H, Gillis D. Anti-cardiolipin antibody testing and reporting practices among laboratories participating in a large external quality assurance program.  Pathology. 2004;  36 174-181
• 32 Favaloro E J, Wong R CW. Laboratory testing and identification of antiphospholipid antibodies and the antiphospholipid syndrome: limitations, standardization, and clinical utility.  Semin Thromb Hemost. 2008;  34 389-410
• 33 Favaloro E J. Standardization, regulation, quality assurance, and emerging technologies in hemostasis: issues, controversies, benefits, and limitations.  Semin Thromb Hemost. 2007;  33 290-297
• 34 Harris E N, Pierangeli S S. Revisiting the anticardiolipin test and its standardization.  Lupus. 2002;  11 269-275
• 35 Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature.  Blood. 2003;  101 1827-1832
• 36 Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome.  Blood. 2003;  102 2717-2723
• 37 Brandt J T, Triplett D A, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.  Thromb Haemost. 1995;  74 1185-1190
• 38 Machin S J, Giddings J C, Greaves M et al.. Guidelines on testing for the lupus anticoagulant.  J Clin Pathol. 1991;  44 885-889
• 39 Green D, Hougie C, Kazmier F J et al.. Report of the Working Party on Acquired Inhibitors of Coagulation: Studies of the “Lupus” Anticoagulant.  Thromb Haemost. 1983;  49 144-146
• 40 Exner T, Triplett D A, Taberner D, Machin S J. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants.  Thromb Haemost. 1991;  65 320-322
• 41 Galli M, Reber G, de Moerloose P, de Groot P G. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome.  J Thromb Haemost. 2008;  6 399-401
• 42 Audrain M A, Colonna F, Morio F, Hamidou M A, Muller J Y. Comparison of different kits in the detection of autoantibodies to cardiolipin and beta2glycoprotein 1.  Rheumatology (Oxford). 2004;  43 181-185
• 43 Zoghlami-Rintelen C, Vormittag R, Sailer T et al.. The presence of IgG antibodies against beta2-glycoprotein I predicts the risk of thrombosis in patients with the lupus anticoagulant.  J Thromb Haemost. 2005;  3 1160-1165
• 44 Galli M. Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome.  Semin Thromb Hemost. 2008;  34 329-334
• 45 Pierangeli S S, Chen P P, Elena R et al.. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms.  Semin Thromb Hemost. 2008;  34 236-250
• 46 Greco T P, Amos M D, Conti-Kelly A M, Naranjo J D, Ijdo J W. Testing for the antiphospholipid syndrome: importance of IgA anti-beta 2-glycoprotein I.  Lupus. 2000;  9 33-41
• 47 Lakos G, Kiss E, Regeczy N et al.. Isotype distribution and clinical relevance of anti-beta2-glycoprotein I (beta2-GPI) antibodies: importance of IgA isotype.  Clin Exp Immunol. 1999;  117 574-579
• 48 Yamada H, Tsutsumi A, Ichikawa K et al.. IgA-class anti-beta2-glycoprotein I in women with unexplained recurrent spontaneous abortion.  Arthritis Rheum. 1999;  42 2727-2728
• 49 Lewis D A, Pound M L, Ortel T L. The reactivity of paired plasma and serum samples are comparable in the anticardiolipin and anti-b2-glycoprotein-1 ELISAs.  J Thromb Haemost. 2006;  4 265-267
• 50 Wong R C, Favaloro E J. The reactivity of paired plasma and serum samples are comparable in the anticardiolipin and anti-beta2-glycoprotein-1 ELISAs: a rebuttal.  J Thromb Haemost. 2006;  4 1434-1435
• 51 Lewis D A, Pound M L, Ortel T L. The reactivity of paired plasma and serum samples are comparable in the anticardiolipin and anti-beta2-glycoprotein-1 ELISAs. Reply to a rebuttal.  J Thromb Haemost. 2006;  4 1435-1437
• 52 Agopian M S, Boctor F N, Peter J B. False-positive test result for IgM anticardiolipin antibody due to IgM rheumatoid factor.  Arthritis Rheum. 1988;  31 1212-1213
• 53 Harris E N. The second international anticardiolipin standardization workshop/the Kingston Antiphospholipid Antibody study (KAPS) group.  Am J Clin Pathol. 1990;  94 476-484
• 54 Levine S R, Salowich-Palm L, Sawaya K L et al.. IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study.  Stroke. 1997;  28 1660-1665
• 55 Escalante A, Brey R L, Mitchell B DJ, Dreiner U. Accuracy of anticardiolipin antibodies in identifying a history of thrombosis among patients with systemic lupus erythematosus.  Am J Med. 1995;  98 559-565
• 56 Finazzi G. The Italian Registry of Antiphospholipid Antibodies.  Haematologica. 1997;  82 101-105
• 57 Pierangeli S S, Harris E N. Clinical laboratory testing for the antiphospholipid syndrome.  Clin Chim Acta. 2005;  357 17-33
• 58 Wasmuth J C, Oliver y Minarro D, Homrighausen A et al.. Phospholipid autoantibodies and the antiphospholipid antibody syndrome: diagnostic accuracy of 23 methods studied by variation in ROC curves with number of clinical manifestations.  Clin Chem. 2002;  48 1004-1010
• 59 Asherson R A. The Primary, secondary, catastrophic, and seronegative variants of the antiphospholipid syndrome: a personal history long in the making.  Semin Thromb Hemost. 2008;  34 227-235
• 60 Wilson W A, Gharavi A E, Koike T et al.. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.  Arthritis Rheum. 1999;  42 1309-1311
• 61 Helbert M, Bodger S, Cavenagh J et al.. Optimising testing for phospholipid antibodies.  J Clin Pathol. 2001;  54 693-698
• 62 Marai I, Gilburd B, Blank M, Shoenfeld Y. Anti-cardiolipin and anti-beta2-glycoprotein I (beta2GP-I) antibody assays as screening for anti-phospholipid syndrome.  Hum Antibodies. 2003;  12 57-62
• 63 Bertolaccini M L, Gomez S, Pareja J F et al.. Antiphospholipid antibody tests: spreading the net.  Ann Rheum Dis. 2005;  64 1639-1643
• 64 Asherson R A, Cervera R. Antiphospholipid antibodies and infections.  Ann Rheum Dis. 2003;  62 388-393
• 65 Moons K GM, Grobbee D E. When should we remain blind and when should our eyes remain open in diagnostic studies?.  J Clin Epidemiol. 2002;  55 633-636
• 66 Swets J A. Measuring the accuracy of diagnostic systems.  Science. 1988;  240 1285-1293
• 67 Ransohoff D F, Feinstein A R. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests.  N Engl J Med. 1978;  299 926-930