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Semin Thromb Hemost 2013; 39(03): 267-271
DOI: 10.1055/s-0033-1334864
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Measurement of Lupus Anticoagulants: An Update on Quality in Laboratory Testing

Murray Adams
1   School of Human Life Sciences, University of Tasmania, Launceston, Tasmania, Australia
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Publication History

Publication Date:
19 February 2013 (online)

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Abstract

Lupus anticoagulants (LAs) are antiphospholipid antibodies that interfere with in vitro phospholipid-dependent clotting tests, but are associated in vivo with significant clinical manifestations such as recurrent pregnancy loss and venous and arterial thrombosis. Although their detection is important for the diagnosis of thrombotic disorders such as the antiphospholipid syndrome, laboratory identification has historically been fraught with many issues. These have included variability in the sensitivity of assays and reagents; high false-negative and false-positive detection rates; a lack of consensus for the use of mixing tests; and, to some extent, lack of compliance with guidelines published by the Lupus Anticoagulant/Antiphospholipid Antibody Scientific Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH). Since the most recently updated guidelines in 2009, external quality assurance (EQA) programs have conducted surveys to provide a “snapshot” of laboratory practices related to the investigation of LA and to identify problems and monitor improvements in testing for LA. This article will review the impact of the most recently updated ISTH guidelines for LA testing and discuss the findings of recent EQA surveys.

Keywords

lupus anticoagulant - antiphospholipid antibodies - quality assurance - guidelines - standardization
 

  • References

  • 1 Feinstein DI, Rapaport SI. Acquired inhibitors of blood coagulation. Prog Hemost Thromb 1972; 1: 75-95
    PubMedGoogle Scholar
  • 2 Pasoto SG, Chakkour HP, Natalino RR , et al. Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sjögren's syndrome. Clin Rheumatol 2012; 31 (9) 1331-1338
    CrossrefPubMedGoogle Scholar
  • 3 Rai RS, Regan L, Clifford K , et al. Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach. Hum Reprod 1995; 10 (8) 2001-2005
    CrossrefPubMedGoogle Scholar
  • 4 Parazzini F, Acaia B, Faden D, Lovotti M, Marelli G, Cortelazzo S. Antiphospholipid antibodies and recurrent abortion. Obstet Gynecol 1991; 77 (6) 854-858
    PubMedGoogle Scholar
  • 5 Boey ML, Colaco CB, Gharavi AE, Elkon KB, Loizou S, Hughes GR. Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. Br Med J (Clin Res Ed) 1983; 287 (6398) 1021-1023
    CrossrefPubMedGoogle Scholar
  • 6 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 (5) 1827-1832
    CrossrefPubMedGoogle Scholar
  • 7 Kampe CE. Clinical syndromes associated with lupus anticoagulants. Semin Thromb Hemost 1994; 20 (1) 16-26
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Favaloro EJ. Trials and tribulations in lupus anticoagulant testing. Clin Chem Lab Med 2013; 51 (2) 253-256
    PubMedGoogle Scholar
  • 9 Favaloro EJ, Wong RC. The antiphospholipid syndrome: a large elephant with many parts or an elusive chameleon disguised by many colours?. Autoimmunity Highlights 2010; 1: 5-14
    CrossrefPubMedGoogle Scholar
  • 10 Favaloro EJ, Wong RC. Laboratory testing for the antiphospholipid syndrome: making sense of antiphospholipid antibody assays. Clin Chem Lab Med 2011; 49 (3) 447-461
    CrossrefPubMedGoogle Scholar
  • 11 Miyakis S, Lockshin MD, Atsumi T , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (2) 295-306
    CrossrefPubMedGoogle Scholar
  • 12 Palatinus A, Adams M. Thrombosis in systemic lupus erythematosus. Semin Thromb Hemost 2009; 35 (7) 621-629
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Reber G, Meijer P. In ECAT veritas?. Lupus 2012; 21 (7) 722-724
    CrossrefPubMedGoogle Scholar
  • 14 Green D, Hougie C, Kazmier FJ , et al. Report of the Working Party on Acquired Inhibitors of Coagulation: studies of the “lupus” anticoagulant. Thromb Haemost 1983; 49 (2) 144-146
    PubMedGoogle Scholar
  • 15 Brandt JT, Triplett DA, 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 (4) 1185-1190
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Exner T, Triplett DA, Taberner D, Machin SJ. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Guidelines for testing and revised criteria for lupus anticoagulants. Thromb Haemost 1991; 65 (3) 320-322
    PubMedGoogle Scholar
  • 17 Pengo V, Tripodi A, Reber G , et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 7 (10) 1737-1740
    CrossrefPubMedGoogle Scholar
  • 18 Favaloro EJ, Bonar R, Zebeljan D, Kershaw G, Marsden K. Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 2010; 8 (12) 2828-2831
    CrossrefPubMedGoogle Scholar
  • 19 Pengo V, Ruffatti A, Legnani C , et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 2010; 8 (2) 237-242
    CrossrefPubMedGoogle Scholar
  • 20 Kershaw G, Suresh S, Orellana D, Nguy YM. Laboratory identification of lupus anticoagulants. Semin Thromb Hemost 2012; 38 (4) 375-384
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Lippi G, Brentegani C, Cocco C, Lo Cascio C, Guidi G. Paradoxical behaviour of lyophilised commercial control materials for CK and CK-MB assays after reconstitution at either 4 degrees C or 24 degrees C. Clin Chim Acta 1997; 261 (2) 167-173
    CrossrefPubMedGoogle Scholar
  • 22 Favaloro EJ, Bonar R, Marsden K. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: Part II—Lupus anticoagulant. Semin Thromb Hemost 2012; 38 (4) 404-411
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Bonar R, Favaloro EJ, Adcock DM. Quality in laboratory diagnostics: from theory to practice. Biochem Med (Zagreb) 2010; 20 (2) 184-199
    PubMedGoogle Scholar
  • 24 Pradella P, Azzarini G, Santarossa L , et al. Cooperation experience in a multicentre study to define the upper limits in a normal population for the diagnostic assessment of the functional lupus anticoagulant assays. Clin Chem Lab Med 2013; 51 (2) 379-385
    PubMedGoogle Scholar
  • 25 Tripodi A. To mix or not to mix in lupus anticoagulant testing? That is the question. Semin Thromb Hemost 2012; 38 (4) 385-389
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Favaloro EJ, Wheatland L, Jovanovich S, Roberts-Thomson P, Wong RC. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: Part I—Anticardiolipin and anti-β2-glycoprotein I antibodies. Semin Thromb Hemost 2012; 38 (4) 390-403
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Bonar R, Favaloro E, Zebeljan D , et al. Evaluating laboratory approaches to the identification of lupus anticoagulants: a diagnostic challenge from the RCPA Haematology QAP. Pathology 2012; 44 (3) 240-247
    CrossrefPubMedGoogle Scholar
  • 28 Tripodi A, Pengo V. More on: laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 2011; 9 (10) 2126-2127
    CrossrefPubMedGoogle Scholar
  • 29 Devreese KM. No more mixing tests required for integrated assay systems in the laboratory diagnosis of lupus anticoagulants?. J Thromb Haemost 2010; 8 (5) 1120-1122
    PubMedGoogle Scholar
  • 30 Martinuzzo ME, Cerrato GS, Varela ML, Adamczuk YP, Forastiero RR. New guidelines for lupus anticoagulant: sensitivity and specificity of cut-off values calculated with plasmas from healthy controls in mixing and confirmatory tests. Int J Lab Hematol 2012; 34 (2) 208-213
    CrossrefPubMedGoogle Scholar
  • 31 Aboud M, Roddie C, Ward C, Coyle L. To mix with pooled normal plasma or not to mix: a comparative study of 2 approaches for assessing lupus anticoagulant inhibitory activity in the dilute Russell viper venom method. Clin Chem 2007; 53 (1) 143-145
    CrossrefPubMedGoogle Scholar
  • 32 Moore GW, Savidge GF. The dilution effect of equal volume mixing studies compromises confirmation of inhibition by lupus anticoagulants even when mixture specific reference ranges are applied. Thromb Res 2006; 118 (4) 523-528
    CrossrefPubMedGoogle Scholar
  • 33 Thom J, Ivey L, Eikelboom J. Normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulant. J Thromb Haemost 2003; 1 (12) 2689-2691
    CrossrefPubMedGoogle Scholar
  • 34 Moffat KA, Ledford-Kraemer MR, Plumhoff EA , et al. Are laboratories following published recommendations for lupus anticoagulant testing? An international evaluation of practices. Thromb Haemost 2009; 101 (1) 178-184
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Dembitzer FR, Ledford Kraemer MR, Meijer P, Peerschke EI. Lupus anticoagulant testing: performance and practices by North American clinical laboratories. Am J Clin Pathol 2010; 134 (5) 764-773
    CrossrefPubMedGoogle Scholar
  • 36 Jennings I, Greaves M, Mackie IJ, Kitchen S, Woods TA, Preston FE. UK National External Quality Assessment Scheme for Blood Coagulation. 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 (2) 364-369
    CrossrefPubMedGoogle Scholar
  • 37 Greaves M, Cohen H, MacHin SJ, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol 2000; 109 (4) 704-715
    CrossrefPubMedGoogle Scholar
  • 38 Tripodi A, Chantarangkul V, Clerici M, Mannucci PM. Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA. Thromb Haemost 2002; 88 (4) 583-586
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Alkayed K, Kottke-Marchant K. Indeterminate lupus anticoagulant results: prevalence and clinical significance. Korean J Hepatol 2011; 46 (4) 239-243
    CrossrefPubMedGoogle Scholar
  • 40 Favaloro EJ, Lippi G. Laboratory testing and/or monitoring of the new oral anticoagulants/antithrombotics: for and against?. Clin Chem Lab Med 2011; 49 (5) 755-757
    CrossrefPubMedGoogle Scholar
  • 41 Favaloro EJ, Lippi G, Koutts J. Laboratory testing of anticoagulants: the present and the future. Pathology 2011; 43 (7) 682-692
    CrossrefPubMedGoogle Scholar
  • 42 Harenberg J, Erdle S, Marx S, Krämer R. Determination of rivaroxaban in human plasma samples. Semin Thromb Hemost 2012; 38 (2) 178-184
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Harenberg J, Giese C, Marx S, Krämer R. Determination of dabigatran in human plasma samples. Semin Thromb Hemost 2012; 38 (1) 16-22
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Tripodi A. Problems and solutions for testing hemostasis assays while patients are on anticoagulants. Semin Thromb Hemost 2012; 38 (6) 586-592
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Favaloro EJ, Lippi G. The new oral anticoagulants and the future of haemostasis laboratory testing. Biochem Med (Zagreb) 2012; 22 (3) 329-341
    PubMedGoogle Scholar
  • 46 de Groot PG, Urbanus RT. The future of antiphospholipid antibody testing. Semin Thromb Hemost 2012; 38 (4) 412-420
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Willis R, Harris EN, Pierangeli SS. Current international initiatives in antiphospholipid antibody testing. Semin Thromb Hemost 2012; 38 (4) 360-374
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Willis R, Harris EN, Pierangeli SS. Pathogenesis of the antiphospholipid syndrome. Semin Thromb Hemost 2012; 38 (4) 305-321
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Teruya J, West AG, Suell MN. Lupus anticoagulant assays: questions answered and to be answered. Arch Pathol Lab Med 2007; 131 (6) 885-889
    PubMedGoogle Scholar