Download PDF
Semin Thromb Hemost 2008; 34(4): 361-372
DOI: 10.1055/s-0028-1085479
© Thieme Medical Publishers

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

Richard C.W Wong1 , Emmanuel J. Favaloro2
  • 1Division of Immunology, Pathology Queensland, Royal Brisbane and Womens Hospital, Herston, Queensland, Australia
  • 2Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, NSW, Australia
Further Information

Publication History

Publication Date:
23 September 2008 (online)

    Permissions and Reprints

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.

KEYWORDS

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
    CrossrefPubMedGoogle Scholar
  • 2 Wong R C, Favaloro E J. Clinical features, diagnosis and management of the antiphospholipid syndrome.  Semin Thromb Hemost. 2008;  34 295-304
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Wong R CW, Gillis D, Adelstein S et al.. Consensus guidelines on anti-cardiolipin antibody testing and reporting.  Pathology. 2004;  36 63-68
    CrossrefPubMedGoogle Scholar
  • 8 Triplett D A. Antiphospholipid antibodies.  Arch Pathol Lab Med. 2002;  126 1424-1429
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 12 Reber G, de Moerloose P. Anti-beta2-glycoprotein I antibodies—when and how should they be measured?.  Thromb Res. 2004;  114 527-531
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Ledford-Kraemer M R. Laboratory testing for lupus anticoagulants: preexamination variables, mixing studies, and diagnostic criteria.  Semin Thromb Hemost. 2008;  34 380-388
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 27 Roussi J, Roisin J P, Goguel A. Lupus anticoagulants: first French interlaboratory Etalonorme survey.  Am J Clin Pathol. 1996;  105 788-793
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Harris E N, Pierangeli S S. Revisiting the anticardiolipin test and its standardization.  Lupus. 2002;  11 269-275
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 56 Finazzi G. The Italian Registry of Antiphospholipid Antibodies.  Haematologica. 1997;  82 101-105
    PubMedGoogle Scholar
  • 57 Pierangeli S S, Harris E N. Clinical laboratory testing for the antiphospholipid syndrome.  Clin Chim Acta. 2005;  357 17-33
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 61 Helbert M, Bodger S, Cavenagh J et al.. Optimising testing for phospholipid antibodies.  J Clin Pathol. 2001;  54 693-698
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 63 Bertolaccini M L, Gomez S, Pareja J F et al.. Antiphospholipid antibody tests: spreading the net.  Ann Rheum Dis. 2005;  64 1639-1643
    CrossrefPubMedGoogle Scholar
  • 64 Asherson R A, Cervera R. Antiphospholipid antibodies and infections.  Ann Rheum Dis. 2003;  62 388-393
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 66 Swets J A. Measuring the accuracy of diagnostic systems.  Science. 1988;  240 1285-1293
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar

Dr. Richard C.W Wong

Division of Immunology, Pathology Queensland (Central Laboratory)

Level 4, Block 7, Royal Brisbane and Womens Hospital, Herston, Queensland 4029, Australia

Email: richard_wong@health.qld.gov.au

      >