Laboratory criteria of the obstetrical antiphospholipid syndrome

Summary

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-β2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS).We report new data on a prospective multicenter European cohort of 109 pregnant women having APS.Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-β2-GPI IgM was present in three women.These results suggest that aCL and a-β2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS.The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.

Keywords

Anticardiolipin antibody - anti-beta2-glycoprotein I antibody - obstetrical antiphospholipid syndrome - thrombotic antiphospholipid syndrome - antiphospholipid syndrome diagnosis

• References

• 1 Wilson WA, Gharavi AE, 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.
• 2 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; 04: 295-306.
• 3 Kist WJ, Janssen NG, Kalk JJ. et al. Thrombophilias and adverse pregnancy outcome – A confounded problem!. Thromb Haemost 2008; 99: 77-85.
• 4 Tincani A, Bazzani C, Zingarelli S. et al. Lupus and the antiphospholipid syndrome in pregnancy and obstetrics: clinical characteristics, diagnosis, pathogenesis and treatment. Sem Thromb Haemost 2008; 34: 267-273.
• 5 Galli M, Reber G, De Moerloose P. et al. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost 2008; 06: 399-401.
• 6 Boffa MC, Aurousseau MH, Lachassinne E. et al. European register of babies born to mothers with antiphospholipid syndrome. Lupus 2004; 13: 713-717.
• 7 Tincani A, Allegri F, Sanmarco M. et al. Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determinations--a ooperative project of the European Antiphospholipid Forum. Thromb Haemost 2001; 86: 575-583.
• 8 Balestrieri G, Tincani A, Spatola L. et al. Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?. Lupus 1995; 04: 122-130.
• 9 Roussel V, Yi F, Jauberteau MO. et al. Prevalence and clinical significance of phospholipid antibodies in multiple sclerosis: a study of 89 patients. J Autoiommun 2000; 14: 259-265.
• 10 Cucnik S, Ambrozic A, Bozic B. et al. Antibeta2-glycoprotein I ELISA: methodology, determination of cut-off values in 434 healthy Caucasians and evaluation of monoclonal antibodies as possible international standards. Clin Chem Lab Med 2000; 38: 777-783.
• 11 Nicaise-Roland P, Aurousseau MH, Delaval A. et al. Levels of anticardiolipin and anti-beta2-glycoprotein1 antibodies in healthy new-born cord sera. Thromb Haemost 2008; 99: 1124-1126.
• 12 Avcin T, Ambrozic A, Bozic B. et al. Estimation of anticardiolipin antibodies, anti-b2 glycoprotein I antibodies and lupus anticoagulant in a prospective longitudinal study of children with juvenile idiopathic arthritis. Clin Exp Rheumatol 2002; 20: 101-108.
• 13 Brandt JT, Triplett DA, Alving B. et al. Criteria for the diagnosis of lupus anticoagulants an update. Thromb Haemost 1995; 74: 1185-1190.
• 14 Pourrat O, Jollit C, Gombert JM. et al. Clinical relevance of the recent update of the classification criteria for definite antiphospholipid syndrome: an obstetrical medicine clinic series of 107 patients. J Thromb Haemost 2006; 04: 295-306.
• 15 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: 178-184.
• 16 Tebo AE, Jaskowski TD, Phansalkar AR. et al. Diagnostic performance of phospholipid-specific assays for the evaluation of antiphospholipid syndrome. Am J Clin Pathol 2008; 129: 870-875.
• 17 Reber G, Tincani A, Sanmarco M. et al. European Forum on Antiphospholipid Antibodies Standardization Group. Variability of anti-beta2-glycoprotein I measurement by commercial assays. Thromb Haemost 2005; 94: 665-672.
• 18 Sanmarco M, Bardin N, Blank M. et al. Heterogeneity of anti-beta2-glycoprotein I antibodies. A factor of variability in test results. Thromb Haemost 2005; 93: 80-87.
• 19 Reber G, Shousboe 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.
• 20 Reber G, Tincani A, Sanmarco M. et al. Proposals for the measurement of anti-ß₂-glycoprotein I antibodies. Standardization Group of the European Forum on Antiphospholipid Antibodies. J Thromb Haemost 2004; 02: 1860-1862.
• 21 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.
• 22 Avcin T. Antiphospholipid syndrome in children. Curr Opin Rheumatol 2008; 20: 595-600.
• 23 Bauersachs RM, Dudenhausen J, Faridi A. et al. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb Haemost 2007; 98: 1237-1245.
• 24 Sanmarco M, Gayet S, Alessi MC. et al. Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis. A multicenter study with the participation of the European Forum on antiphospholipid antibodies. Thromb Haemost 2007; 97: 949-954.