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The antiphospholipid syndrome: a large elephant with many parts or an elusive chameleon disguised by many colours?

Autoimmunity Highlights volume 1, pages5–14(2010)Cite this article

Abstract

The antiphospholipid syndrome (APS) is characterized by a range of clinical features (primarily thrombosis and/or obstetric-related), together with the presence of antiphospholipid antibody (aPL) as detected by a diverse range of laboratory tests. APS remains a significant diagnostic and management challenge for clinicians across a wide range of specialties, some 30 years after APS was first described as a discrete clinical entity. This is due to ongoing issues regarding nomenclature, the diagnosis of APS in individual patients, the expanding range of recognized clinical manifestations and of APS-related laboratory tests, and management issues in particular APS patient subgroups (including obstetric and catastrophic APS). In addition to the presence of appropriate clinical features, the diagnosis of APS fundamentally requires the finding of positive aPL test result(s), which is hampered by ongoing problems with assay reproducibility and standardization. This review focuses on ongoing dilemmas and issues related to clinical and laboratory aspects of APS including: (1) diagnostic challenges posed by the protean clinical manifestations of APS; (2) current nomenclature and recent proposals for revision of the 2006 international classification criteria; (3) an overview of some key issues related to aPL testing; (4) potential pitfalls of applying the APS classification criteria as diagnostic criteria; and (5) the controversial subgroups of seronegative APS and non-APS aPL positivity.

References

  1. 1.

    Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306

  2. 2.

    Hughes GR (2007) Hughes syndrome. The antiphospholipid syndrome — a clinical overview. Clin Rev Allergy Immunol 32:3–11

  3. 3.

    Harris EN, Pierangeli SS (2008) Primary, secondary and catastrophic antiphospholipid syndrome: what’s in a name? Semin Thromb Hemost 34:219–226

  4. 4.

    Asherson RA (2008) The primary, secondary, catastrophic and seronegative variants of the antiphospholipid syndrome: A personal history long in the making. Semin Thromb Hemost 34:227–235

  5. 5.

    Roubey R (1996) Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum 39:1444–1454

  6. 6.

    Wong RC, Favaloro EJ (2008) Clinical features, diagnosis and management of the antiphospholipid syndrome. Semin Thromb Hemost 34:295–304

  7. 7.

    Palatinus A, Adams M (2009) Thrombosis in systemic lupus erythematosus. Semin Thromb Hemost 35:621–629

  8. 8.

    Siesdedos L, Munoz-Rodriguez FJ, Cervera R et al (1997) Primary antiphospholipid syndrome evolving into systemic lupus erythematosus. Lupus 6:285–286

  9. 9.

    Asherson RA, Cervera R, Merrill JT et al (2008) Antiphospholipid antibodies and the antiphospholipid syndrome: clinical significance and treatment. Semin Thromb Hemost 34:256–266

  10. 10.

    Mehdi AA, Salti I, Uthman I. Antiphospholipid syndrome: endocrinologic manifestations and organ involvement. Semin Thromb Hemost 2010 (in press)

  11. 11.

    Blume JE, Miller CC (2006) Antiphospholipid syndrome: a review and update for the dermatologist. Cutis 78:409–415

  12. 12.

    Miesbach W (2008) Neurological symptoms as a feature of the antiphospholipid syndrome. Semin Thromb Hemost 34:286–289

  13. 13.

    Miesbach W (2008) Antiphospholipid antibodies and antiphospholipid syndrome in patients with malignancies: features, incidence, identification and treatment. Semin Thromb Hemost 34:282–285

  14. 14.

    Tincani A, Bazzani C, Zingarelli S et al (2008) Lupus and the antiphospholipid syndrome in pregnancy and obstetrics: clinical characteristics, diagnosis, pathogenesis and treatment. Semin Thromb Hemost 34:267–273

  15. 15.

    Pierangeli SS, Chen PP, Raschi E et al (2008) Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost 34:236–250

  16. 16.

    Meroni PL, Tincani A. 12th International Congress on Anti-Phospholipid Antibodies. Florence, 18–20 April 2007. http://www.antiphospholipid.net/committees.html. Accessed 20th March 2010

  17. 17.

    Galli M, Reber G, de Moerloose P et al (2008) Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost 6:399–401

  18. 18.

    Favaloro EJ, Wong RC (2008) Laboratory testing and identification of antiphospholipid antibodies and the antiphospholipid syndrome II: Limitations, standardisation and clinical utility. Semin Thromb Hemost 34:309–312

  19. 19.

    Favaloro EJ, Wong RC (2008) Laboratory testing and identification of antiphospholipid antibodies and the antiphospholipid syndrome: a potpourri of problems, a compilation of possible solutions. Semin Thromb Hemost 34:389–410

  20. 20.

    Pengo V, Ruffatti A, Legnani C et al (2010) Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 8:237–242

  21. 21.

    Galli M (2010) The antiphospholipid triangle. J Thromb Haemost 8:234–236

  22. 22.

    Pengo V, Biasiolo A, Pegoraro C et al (2005) Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 93:147–152

  23. 23.

    Ruffatti A, Tonello M, Cavazzana A et al (2009) Laboratory classification categories and pregnancy outcome in patients with primary antiphospholipid syndrome prescribed antithrombotic therapy. Thromb Res 123:482–427

  24. 24.

    Ruffatti A, Tonello M, Del Ross T et al (2006) Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity. Thromb Haemost 96:337–341

  25. 25.

    Favaloro EJ, Wong RC (2009) Current clinical and laboratory practice for the investigation of the antiphospholipid syndrome: findings from the 2008 Australasian antiphospholipid antibody survey. Pathology 41:666–675

  26. 26.

    Pierangeli SS, Harris EN (2008) A quarter of a century in anticardiolipin antibody testing and attempted standardization has led us to here, which is? Semin Thromb Hemost 34:313–328

  27. 27.

    Andreoli L, Rizzini S, Allegri S et al (2008) Are the current attempts at standardisation of antiphospholipid antibodies still useful? Emerging technologies signal a shift in direction. Semin Thromb Hemost 34:356–360

  28. 28.

    Reber G, Boehlen F, de Moerloose P (2008) Technical aspects in laboratory testing for antiphospholipid antibodies: is standardisation an impossible dream? Semin Thromb Hemost 34:340–346

  29. 29.

    Favaloro EJ, Wong RC, Silvestrini R et al (2005) A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin antibody, and beta2-glycoprotein I antibody testing. Semin Thromb Hemost 31:73–84

  30. 30.

    Favaloro EJ, Silvestrini R (2002) 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 118:548–557

  31. 31.

    Reber G, Arvieux J, Comby E et al (1995) 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 73:444–452

  32. 32.

    Tincani A, Filippini M, Scarsi M et al (2009) European attempts for the standardisation of the antiphospholipid antibodies. Lupus 18:913–919

  33. 33.

    Pengo V, Tripodi A, Reber G et al (2009) Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 7:1737–1740

  34. 34.

    Wong RC, Wilson RJ, Pollock W et al (2004) Anti-cardiolipin antibody testing and reporting practices among laboratories participating in a large external quality assurance program. Pathology 36:174–181

  35. 35.

    Wong RC, Gillis D, Adelstein S et al (2004) Consensus guidelines on anti-cardiolipin antibody testing and reporting. Pathology 36:63–68

  36. 36.

    Wong RC, Favaloro EJ, Adelstein S et al (2008) Consensus guidelines on anti-beta 2 glycoprotein I testing and reporting. Pathology 40:58–63

  37. 37.

    Galli M, Luciani D, Bertolini G et al (2003) Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 101:1827–1832

  38. 38.

    Galli M, Luciani D, Bertolini G et al (2003) Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 102:2717–2723

  39. 39.

    Wilson WA, Gharavi AE, Koike T et al (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311

  40. 40.

    Lockshin MD, Sammaritano LR, Schwartzman S (2000) Validation of the Sapporo criteria for antiphospholipid syndrome. Arthritis Rheum 43:440–443

  41. 41.

    Galli M (2008) Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome. Semin Thromb Hemost 34:329–334

  42. 42.

    de Groot PG, Derksen RH, de Laat B (2008) Twenty-two years of failure to set-up undisputed assays to detect patients with the antiphospholipid antibodies. Semin Thromb Hemost 34:347–355

  43. 43.

    Wong RC, Favaloro EJ (2008) A consensus approach to the formulation of guidelines for laboratory testing and reporting of antiphospholipid antibody assays. Semin Thromb Hemost 34:361–372

  44. 44.

    Miret C, Cervera R, Reverter JC et al (1997) Antiphospholipid syndrome without antiphospholipid antibodies at the time of the thrombotic event: transient ’seronegative’ antiphospholipid syndrome? Clin Exp Rheumatol 15:541–544

  45. 45.

    Bland MJ, Altman DG (1995) Multiple significance tests: the Bonferroni method. BMJ 310:170

  46. 46.

    Metjian A, Lim W (2009) ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis? Hematology Am Soc Hematol Educ Program pp 247–249

  47. 47.

    Helbert M, Bodger S, Cavenagh J et al (2001) Optimising testing for phospholipid antibodies. J Clin Pathol 54:693–698

  48. 48.

    Erkan D, Harrison MJ, Levy R et al (2007) Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum 56:2382–2391

  49. 49.

    Devreese K, Hoylaerts MF (2009) Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome. Eur J Haematol 83:1–16

  50. 50.

    Hunt BJ (2008) Paediatric antiphospholipid antibodies and antiphospholipid syndrome. Semin Thromb Hemost 34:274–281

  51. 51.

    Espinosa G, Bucciarelli S, Asherson RA et al (2008) Morbidity and mortality in the catastrophic antiphospholipid syndrome: pathophysiology, causes of death and prognostic factors. Semin Thromb Hemost 34:290–294

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Affiliations

  1. Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, WSAHS, Westmead, NSW, 2145, Australia
    • Emmanuel J. Favaloro
  2. Division of Immunology, Pathology Queensland Central Laboratory, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia
    • Richard C. W. Wong
Authors
  1. Emmanuel J. Favaloro
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  2. Richard C. W. Wong
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Correspondence to Emmanuel J. Favaloro.

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Favaloro, E.J., Wong, R.C.W. The antiphospholipid syndrome: a large elephant with many parts or an elusive chameleon disguised by many colours?. Autoimmun Highlights 1, 5–14 (2010). https://doi.org/10.1007/s13317-010-0003-7

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Keywords

  • Anti-beta-2-glycoprotein-I antibodies
  • Anticardiolipin antibodies
  • Antiphospholipid antibodies
  • aPL
  • Antiphospholipid syndrome
  • APS
  • Clinical features
  • Criteria
  • Diagnosis

Autoimmunity Highlights

ISSN: 2038-3274

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