Semin Thromb Hemost 2005; 31(1): 73-84
DOI: 10.1055/s-2005-863808
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

A Multilaboratory Peer Assessment Quality Assurance Program-Based Evaluation of Anticardiolipin Antibody, and beta2-Glycoprotein I Antibody Testing

Emmanuel J. Favaloro1 , 2 , Richard C. W. Wong4 , Roger Silvestrini3 , Robert McEvoy5 , Susan Jovanovich5 , Peter Roberts-Thomson5
  • 1Senior Scientist in Charge, Haemostasis Laboratories, Departments of Haematology and Immunopathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Walls, Australia
  • 2Department of Haematology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Walls, Australia
  • 3Department Immunopathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Walls, Australia
  • 4Division of Immunology, Queensland Health Pathology Services, Princess Alexandra & Royal Brisbane Hospitals, Brisbane, Australia
  • 5Royal College of Pathologists of Australasia Quality Assurance Program Pty Ltd, Flinders Medical Centre, Adelaide, Australia
Further Information

Publication History

Publication Date:
11 February 2005 (online)

ABSTRACT

We evaluated the performance of anticardiolipin (aCL) and beta2-glycoprotein I (β2-GPI) antibody assays through a large external quality assurance program. Data from the 2002 cycle of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were analyzed for variation in reported numerical values and semiquantitative results or interpretations according to method type or group and in conjunction with available clinical data. High interlaboratory variation in numerical results and notable method-based variation, combined with a general lack of consensus in semiquantitative reporting, continues to be observed. Numerical results from cross-laboratory testing of 12 serum samples (for immunoglobulin G [IgG]-aCL, IgM-aCL, and IgG-β2-GPI) yielded interlaboratory coefficients of variation (CVs) that were higher than 50% in six of 12 (50%) specimens for IgG-aCL, and 12 of 12 (100%) specimens for IgM-aCL and IgG-β2-GPI. Semiquantitative reporting also varied considerably, with total (100%) consensus occurring in only four of 36 (11%) occasions. General consensus (where > 90% of participating laboratories agreed that a given serum sample gave a result of either negative or positive) was only obtained on 13 of 36 (36%) occasions. Variation in results between different method types or groups were also present, resulting in potential biasing of the RCPA QAP-defined target results by the large number of laboratories using the dominant aCL assays. Finally, laboratory findings frequently did not agree with the available clinical information. In conclusion, in a large proportion of specimens from the 2002 RCPA QAP cycle, laboratories could not agree on whether a serum sample tested was aCL-positive or aCL-negative, or β2-GPI-positive or β2-GPI-negative. Despite prior attempts to improve the standardization of testing and reporting practices, laboratory testing for aCL and anti-β2-GPI still demonstrates significant interlaboratory and intermethod variation, which needs to be taken into account for the clinical interpretation of test results, especially those from different laboratories.

REFERENCES

  • 1 Harris E N. Antiphospholipid antibodies.  Br J Haematol. 1990;  74 1-9
  • 2 Field S L, Brighton T A, McNeil H P, Chesterman C N. Recent insights into antiphospholipid antibody-mediated thrombosis.  Baillieres Best Pract Res Clin Haematol. 1999;  12 407-422
  • 3 Merrill J T. Which antiphospholipid antibody tests are most useful? .  Rheum Dis Clin North Am. 2001;  27 525-549
  • 4 Harris E N, Gharavi A EM, Boey M L et al.. Anti-cardiolipin antibodies: detection by radio-immunoassay and association with thrombosis in systemic lupus erythematosus.  Lancet. 1983;  2 1211-1214
  • 5 Triplett D A, Brandt J T, Musgrave K A, Orr C A. The relationship between lupus anticoagulants and antibodies to phospholipid.  JAMA. 1988;  259 550-554
  • 6 Ginsberg J S, Wells P S, Brill-Edwards P et al.. Antiphospholipid antibodies and venous thromboembolism.  Blood. 1995;  86 3685-3691
  • 7 Pengo V, Thiagarajan P, Shapiro S S, Heine M J. Immunological specificity and mechanism of action of IgG lupus anticoagulants.  Blood. 1987;  70 69-76
  • 8 Harris E N, Chan J KH, Asherson R A, Aber V A, Gharavi A E, Hughes G RV. Thrombosis, recurrent fetal loss, thrombocytopenia: predictive value of IgG anticardiolipin antibodies.  Arch Intern Med. 1986;  146 2153-2156
  • 9 Ginsberg K S, Liang M H, Newcomer L et al.. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis.  Ann Intern Med. 1992;  117 997-1002
  • 10 Court E L. Lupus anticoagulants: pathogenesis and laboratory diagnosis.  Br J Biomed Sci. 1997;  54 287-298
  • 11 Galli M, Finazzi G, Barbui T. Antiphospholipid antibodies: predictive value of laboratory tests.  Thromb Haemost. 1997;  77 75-78
  • 12 Vermylen J, Hoylaerts M F, Arnout J. Antibody-mediated thrombosis.  Thromb Haemost. 1997;  78 420-426
  • 13 Hughes GRV. The antiphospholipid syndrome: ten years on.  Lancet. 1993;  342 341-344
  • 14 McNeil H P, Krillis S A. Antiphospholipid antibodies.  Aust N Z J Med. 1991;  21 463-475
  • 15 Triplett D A. Protean clinical presentation of antiphospholipid antibodies (APA).  Thromb Haemost. 1995;  74 329-337
  • 16 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
  • 17 Immunology Quality Assurance Program, RCPA .Available at: www.rcpaqap.com.au/immunology. Accessed February 2 2004
  • 18 Harris E N, Gharavi A E, Patel S P, Hughes G RV. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986.  Clin Exp Immunol. 1987;  68 215-222
  • 19 Favaloro E J, Silvestrini R, Mohammed A. Clinical utility of anticardiolipin antibody assays: High inter-laboratory variation and limited consensus by participants of external Quality Assurance Programs signals a cautious approach.  Pathology. 1999;  31 142-147
  • 20 Favaloro E J, Silvestrini R. Assessing the utility of anticardiolipin antibody assays: a cautious approach is suggested by high variation and limited consensus in multi-laboratory testing.  Am J Clin Pathol. 2002;  118 548-557
  • 21 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
  • 22 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
  • 23 Triplett D A. Antiphospholipid antibodies.  Arch Pathol Lab Med. 2002;  126 1424-1429
  • 24 Harris E N, Pierangeli S S. Revisiting the anticardiolipin test and its standardization.  Lupus. 2002;  11 269-275
  • 25 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
  • 26 Tomar R H. Chair, on behalf of the Diagnostic Resource Committee. Antiphospholipid Antibody Survey Set ACL .Northfield, IL; US College of American Pathologists 1999
  • 27 Ichikawa K, Tsutsumi A, Atsumi T et al.. A chimeric antibody with the human gamma1 constant region as a putative standard for assays to detect IgG beta2-glycoprotein I-dependent anticardiolipin and anti-beta2-glycoprotein I antibodies.  Arthritis Rheum. 1999;  42 2461-2470
  • 28 Wong R C, Gillis D, Adelstein S et al.. Consensus guidelines on anti-cardiolipin antibody testing and reporting.  Pathology. 2004;  36 63-68
  • 29 Galli M, Luciani D, Bertolini G, Barbui T. Anti-B2-glycoprotein I, antiprothrombin antibodies and the risk of thrombosis in the antiphospholipid syndrome.  Blood. 2003;  102 2717-2723

 Dr.
E. J FavaloroPh.D. 

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR)

WSAHS, Westmead, New South Walls, 2145, Australia

Email: emmanuel@icpmr.wsahs.nsw.gov.au

    >