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• Comments on the Reassessment of the 2006 revised antiphospholipid syndriome classification criteria
  Antonio R. Cabral
  Published on: 22 March 2007

• Published on: 22 March 2007

  Comments on the Reassessment of the 2006 revised antiphospholipid syndriome classification criteria

  • Antonio R. Cabral, Research Investigator
  • Other Contributors:
    • Javier Cabiedes

  Dear Editor, The recent retrospective study by Kaul et al(1) on the assessment of the 2006 revised classification criteria for definite antiphospholipid syndrome (2) sets the ground for at least three issues. a) The inclusion of “non-criteria aPL features” in the revised APS criteria is indeed a step forward, but it appears that it requires revaluation, particularly with regards to the addition of thrombocytopenia as a dist...

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  Dear Editor, The recent retrospective study by Kaul et al(1) on the assessment of the 2006 revised classification criteria for definite antiphospholipid syndrome (2) sets the ground for at least three issues. a) The inclusion of “non-criteria aPL features” in the revised APS criteria is indeed a step forward, but it appears that it requires revaluation, particularly with regards to the addition of thrombocytopenia as a distinct clinical criteria. As known, this hematological manifestation was amongst the first clinical features recognized as part of the syndrome (3), it is actually more frequent than pregnancy morbidity in large series of APS patients (4,5) and, aCL and anti-ß2-glycoprotein-I antibodies (anti-ß2GP-I) bind strongly to activated platelets in vitro via ß2GP-I (6).

  In Kaul’s series, 16 patients with aPL had thrombocytopenia (11 had a vascular event and 5 were classified as being “asymptomatic”) while 9 patients fulfilled the pregnancy morbidity as the only criteria for APS. b) Four patients (10%) had APS according to the 2006 criteria, but not by the 1998 criteria, due to the fact that those patients fulfilled the IIc serological criteria, that is, they had anti-ß2GP-I as the only antibody. This is in agreement with earlier papers that reported the existence of aCL-negative, anti-ß2GP -I-positive patients, with or without systemic lupus erythematosus (SLE), but with otherwise clinical manifestations of the APS (7,8). Kaul´s finding also confirms that aCL (-), LAC (-), anti-ß2GP-I (+) patients account for 5-10% of patients with antiphospholipid syndrome (9,10). c) Kaul´s et al studied 82 “asymptomatic” patients, 39 of them met at least one serological criteria for APS; assuming that the remainder 43 patients were asymptomatic and aPL negative, the sensitivity and specificity of aCL alone for APS is 0.28 and 0.67, 0.09 and 0.98 for anti-ß2GP-I alone, 0.28 and 0.59 for more than one aPL and 0.52 and 0.52 for all serological criteria, respectively. This finding confirms previous data showing that aCL have high sensitivity and low specificity for APS while anti-ß2GP-I have higher specificity and lower sensitivity than aCL for APS.

  More than a decade ago, it has been our contention that antibodies toß2GP-I are comprised by at least two subpopulations, one directed against a cryptic epitope (detected by the conventional aCL ELISA) and another one reactive with the native protein (detected by the modified ELISA with purified ß2GP-I as antigen). Thus, both immunoassays detect antibodies to ß2GP-I, while the conventional aCL ELISA also detects antibodies reactive with cardiolipin proper (authentic aCL). This latter phenomenon may thus explain the low specificity of aCL for APS (In Kual´s series, 54% of asymptomatic patients had aCL).

  The Sapporo APS criteria were developed by the experts’ opinions on the subject, while the amended criteria were born after an appraisal of the existing evidence on clinical and laboratory features of APS 1. What it is clearly needed is a large multinational study to objectively and prospectively validate the revised criteria and, why not, to challenge them with those developed 15 years ago after the systematic study of 667 patients with SLE 4

  References

  1. Kaul MS, Erkan D, Sammaritano L, Lockshin MD. Assessment of the 2006 revised antiphospholipid syndrome classification criteria. Ann Rheum Dis 2007.

  2. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306.

  3. Hughes GRV. Hughes' syndrome: the antiphospholipid syndrome. A historical view. Lupus 1998;2:1-4.

  4. Alarcón-Segovia D, Pérez-Vázquez ME, Villa AR, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum 1992;21:275-86.

  5. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MTet al. Antiphospholipid syndrome. Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum 2002;46:1019-27.

  6. Vázquez-Mellado J, Llorente L, Alarcón-Segovia D. Exposure of anionic phospholipids upon platelet activation permits binding of ß2-glycoprotein-I and through it IgG antiphospholipid antibodies. Studies in platelets from patients with antiphospholipid syndrome and normal subjects. J Autoimmunity 1994;7:335-48.

  7. Cabral AR, Amigo MC, Cabiedes J, Alarcón-Segovia D. The antiphospholipid/cofactor syndromes. A primary variant with antibodies to ß2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. Am J Med 1996;101:472-81.

  8. Alarcón-Segovia D, Mestanza M, Cabiedes J, Cabral AR. The antiphospholipid/cofactor syndromes. II. A variant in patients with systemic lupus erythematosus with antibodies to ß2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. J Rheumatol 1997;24:1545-51.

  9. Damoiseaux J, Wijffels M, Willems GM, Bevers EM, Spaanderman ME, van Pampus EC et al. The antiphospholipid/cofactor syndrome: results of routine screening for antibodies to ß2-GPI upon suspicion of the antiphospholipid syndrome. Scand J Rheumatol 2004;33(6):441-2.

  10. 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;102:2717-23.

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  Conflict of Interest:
  None declared.

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