Skip to main content
Top
Published in: Journal of Thrombosis and Thrombolysis 2/2018

01-08-2018

Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome

Authors: Amihai Rottenstreich, Ariela Arad, Hadas Terespolsky, Uriel Elchalal, Hagai Amsalm, Batia Roth, Yosef Kalish

Published in: Journal of Thrombosis and Thrombolysis | Issue 2/2018

Login to get access

Abstract

Antiphospholipid syndrome (APLS) is caused by antiphospholipid autoantibodies, and manifests with vascular and/or obstetric complications. The factors associated with initial disease presentation and course are unknown. We assessed the antibody profile associated with disease presentation and with the development of vascular and obstetric complications in women with initially vascular or initially obstetric APLS. A review of records of APLS women at childbearing age followed at one center during 2006–2015. Of 126 women, median age at diagnosis 29 [23–37] years, 62 were initially diagnosed with purely obstetric APLS and 64 with purely vascular APLS. Baseline characteristics and antibody profile did not differ according to the initial diagnosis. At a mean follow-up duration of 61 ± 23 months, 19 (30.6%) with initially obstetric disease, and 20 (31.3%) with initially vascular disease, developed vascular and obstetric complications, respectively (P = 1.0). Among those with triple positivity [lupus anticoagulant (LAC)+, anticardiolipin (ACL)+, anti beta2-glycoprotein I (AB2GPI)+], a higher proportion developed both obstetric and vascular complications, compared to those with single or double positivity (42.3 vs. 16.4%, P = 0.002). In multivariate analysis, the presence of LAC (P = 0.008), ACL IgG (P = 0.009) or AB2GPI IgG (P = 0.01) was the only independent predictor of the development of both obstetric and vascular complications. Almost one-third of women with initially vascular or initially obstetric APLS developed mixed disease. The antibody profile was the only prognostic marker for disease course. The association found between LAC, ACL IgG or AB2GPI IgG, and patient outcomes could contribute to risk stratification and individualized patient management.
Literature
1.
go back to reference Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Lakos G, Tincani A, Kontopoulou-Griva I, Galeazzi M, Meroni PL, Derksen RHWM., De Groot PG, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC et al (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheumatol 46:1019–1027CrossRef Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Lakos G, Tincani A, Kontopoulou-Griva I, Galeazzi M, Meroni PL, Derksen RHWM., De Groot PG, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC et al (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheumatol 46:1019–1027CrossRef
2.
3.
go back to reference Cervera R, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Kiss E, Zeher MM, Tincani A, Kontopoulou-Griva I, Galeazzi M, Bellisai F, Meroni PL, Derksen RHWM., De Groot PG, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC et al (2009) Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 68:1428–1432CrossRefPubMed Cervera R, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Kiss E, Zeher MM, Tincani A, Kontopoulou-Griva I, Galeazzi M, Bellisai F, Meroni PL, Derksen RHWM., De Groot PG, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC et al (2009) Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 68:1428–1432CrossRefPubMed
4.
go back to reference Gris JC, Bouvier S, Nouvellon E, Lissalde-Lavigne G, Mercier E, Balducchi JP, Marès P (2017) Antiphospholid antibodies and the risk of pregnancy complications. Thromb Res 151:S34–S37CrossRefPubMed Gris JC, Bouvier S, Nouvellon E, Lissalde-Lavigne G, Mercier E, Balducchi JP, Marès P (2017) Antiphospholid antibodies and the risk of pregnancy complications. Thromb Res 151:S34–S37CrossRefPubMed
5.
go back to reference Brusch A (2016) The significance of anti-beta-2-glycoprotein i antibodies in antiphospholipid syndrome. Antibodies 5:16CrossRef Brusch A (2016) The significance of anti-beta-2-glycoprotein i antibodies in antiphospholipid syndrome. Antibodies 5:16CrossRef
6.
go back to reference Kelchtermans H, Pelkmans L, de Laat B, Devreese KM (2016) IgG/IgM antiphospholipid antibodies present in the classification criteria for the antiphospholipid syndrome: a critical review of their association with thrombosis. J Thromb Haemost 14:1530–1548CrossRefPubMed Kelchtermans H, Pelkmans L, de Laat B, Devreese KM (2016) IgG/IgM antiphospholipid antibodies present in the classification criteria for the antiphospholipid syndrome: a critical review of their association with thrombosis. J Thromb Haemost 14:1530–1548CrossRefPubMed
7.
go back to reference Opatrny L, David M, Kahn SR, Shrier I, Rey E (2006) Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J Rheumatol 33:2214–2221PubMed Opatrny L, David M, Kahn SR, Shrier I, Rey E (2006) Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J Rheumatol 33:2214–2221PubMed
8.
go back to reference Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306CrossRefPubMed Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306CrossRefPubMed
9.
go back to reference Brandt JT, Triplett DA, Alving B, Scharrer I (1995) 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 74:1185–1190CrossRefPubMed Brandt JT, Triplett DA, Alving B, Scharrer I (1995) 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 74:1185–1190CrossRefPubMed
10.
go back to reference Tincani A, Allegri F, Sanmarco M, Cinquini M, Taglietti M, Balestrieri G, Koike T, Ichikawa K, Meroni P, Boffa MC (2001) Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determination—a cooperative project of the European Antiphospholipid Forum. Thromb Haemost 86:575–583CrossRefPubMed Tincani A, Allegri F, Sanmarco M, Cinquini M, Taglietti M, Balestrieri G, Koike T, Ichikawa K, Meroni P, Boffa MC (2001) Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determination—a cooperative project of the European Antiphospholipid Forum. Thromb Haemost 86:575–583CrossRefPubMed
11.
go back to reference Reber G, Tincani A, Sanmarco M, de Moerloose P, Boffa MC (2004) Proposals for the measurement of anti-beta2-glycoprotein I antibodies. Standardization group of the European Forum on Antiphospholipid Antibodies. J Thromb Haemost 2:1860–1862CrossRefPubMed Reber G, Tincani A, Sanmarco M, de Moerloose P, Boffa MC (2004) Proposals for the measurement of anti-beta2-glycoprotein I antibodies. Standardization group of the European Forum on Antiphospholipid Antibodies. J Thromb Haemost 2:1860–1862CrossRefPubMed
12.
go back to reference Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, Rizzo N, Facchinetti F, Dall’Asta A, Visentin S, Sarno L, Xodo S, Bernabini D, Monari F, Roman A, Eke AC, Hoxha A, Ruffatti A, Schuit E, Martinelli P (2017) Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol 216:525.e1–525.e12PubMed Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, Rizzo N, Facchinetti F, Dall’Asta A, Visentin S, Sarno L, Xodo S, Bernabini D, Monari F, Roman A, Eke AC, Hoxha A, Ruffatti A, Schuit E, Martinelli P (2017) Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol 216:525.e1–525.e12PubMed
13.
go back to reference Chauleur C, Galanaud JP, Alonso S, Cochery-Nouvellon E, Balducchi JP, Marès P, Fabbro-Peray P, Gris JC (2010) Observational study of pregnant women with a previous spontaneous abortion before the 10th gestation week with and without antiphospholipid antibodies. J Thromb Haemost 8:699–706CrossRefPubMed Chauleur C, Galanaud JP, Alonso S, Cochery-Nouvellon E, Balducchi JP, Marès P, Fabbro-Peray P, Gris JC (2010) Observational study of pregnant women with a previous spontaneous abortion before the 10th gestation week with and without antiphospholipid antibodies. J Thromb Haemost 8:699–706CrossRefPubMed
14.
go back to reference Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE (2012) Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum 64:2311–2318CrossRefPubMedPubMedCentral Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE (2012) Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum 64:2311–2318CrossRefPubMedPubMedCentral
15.
go back to reference Gris JC, Bouvier S, Molinari N, Galanaud JP, Cochery-Nouvellon É, Mercier É, Fabbro-Peray P, Balducchi JP, Marès P, Quéré I, Dauzat M (2012) Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 119:2624–2632CrossRefPubMed Gris JC, Bouvier S, Molinari N, Galanaud JP, Cochery-Nouvellon É, Mercier É, Fabbro-Peray P, Balducchi JP, Marès P, Quéré I, Dauzat M (2012) Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 119:2624–2632CrossRefPubMed
16.
go back to reference Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, Lockshin MD, Petri M, Merrill JT, Sammaritano LR, Kim MY, Salmon JE (2016) Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med 3:e000131CrossRefPubMedPubMedCentral Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, Lockshin MD, Petri M, Merrill JT, Sammaritano LR, Kim MY, Salmon JE (2016) Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med 3:e000131CrossRefPubMedPubMedCentral
17.
go back to reference Alijotas-Reig J, Ferrer-Oliveras R, Ruffatti A, Tincani A, Lefkou E, Bertero MT, Coloma-Bazan E, de Carolis S, Espinosa G, Rovere-Querini P, Kuzenko A, Valverde EE, Robles A, Cervera R, Canti V, Fredi M, Gil-Aguado A, Lundelin K, Llurba E, Melnychuk T et al (2015) The European Registry on obstetric antiphospholipid syndrome (EUROAPS): a survey of 247 consecutive cases. Autoimmun Rev 14:387–395CrossRefPubMed Alijotas-Reig J, Ferrer-Oliveras R, Ruffatti A, Tincani A, Lefkou E, Bertero MT, Coloma-Bazan E, de Carolis S, Espinosa G, Rovere-Querini P, Kuzenko A, Valverde EE, Robles A, Cervera R, Canti V, Fredi M, Gil-Aguado A, Lundelin K, Llurba E, Melnychuk T et al (2015) The European Registry on obstetric antiphospholipid syndrome (EUROAPS): a survey of 247 consecutive cases. Autoimmun Rev 14:387–395CrossRefPubMed
18.
go back to reference Ruffatti A, Tonello M, Cavazzana A, Bagatella P, Pengo V (2009) Laboratory classification categories and pregnancy outcome in patients with primary antiphospholipid syndrome prescribed antithrombotic therapy. Thromb Res 123:482–487CrossRefPubMed Ruffatti A, Tonello M, Cavazzana A, Bagatella P, Pengo V (2009) Laboratory classification categories and pregnancy outcome in patients with primary antiphospholipid syndrome prescribed antithrombotic therapy. Thromb Res 123:482–487CrossRefPubMed
19.
go back to reference Ruffatti A, Tonello M, Visentin MS, Bontadi A, Hoxha A, De Carolis S, Botta A, Salvi S, Nuzzo M, Rovere-Querini P, Canti V, Mosca M, Mitic G, Bertero MT, Pengo V, Boffa MC, Tincani A (2011) Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology 50:1684–1689CrossRefPubMed Ruffatti A, Tonello M, Visentin MS, Bontadi A, Hoxha A, De Carolis S, Botta A, Salvi S, Nuzzo M, Rovere-Querini P, Canti V, Mosca M, Mitic G, Bertero MT, Pengo V, Boffa MC, Tincani A (2011) Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology 50:1684–1689CrossRefPubMed
20.
go back to reference Stojanovich L, Markovic O, Marisavljevic D, Elezovic I, Ilijevski N, Stanisavljevic N (2012) Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study. Lupus 21:338–345CrossRefPubMed Stojanovich L, Markovic O, Marisavljevic D, Elezovic I, Ilijevski N, Stanisavljevic N (2012) Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study. Lupus 21:338–345CrossRefPubMed
21.
go back to reference Marchetti T, de Moerloose P, Gris JC (2016) Antiphospholipid antibodies and the risk of severe and non-severe pre-eclampsia: The NOHA case-control study. J Thromb Haemost 14:675–684CrossRefPubMed Marchetti T, de Moerloose P, Gris JC (2016) Antiphospholipid antibodies and the risk of severe and non-severe pre-eclampsia: The NOHA case-control study. J Thromb Haemost 14:675–684CrossRefPubMed
22.
go back to reference Arad A, Proulle V, Furie RA, Furie BC, Furie B (2011) Beta2 glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model. Blood 117(24):3453–3459CrossRefPubMedPubMedCentral Arad A, Proulle V, Furie RA, Furie BC, Furie B (2011) Beta2 glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model. Blood 117(24):3453–3459CrossRefPubMedPubMedCentral
23.
go back to reference Neville C, Rauch J, Kassis J, Chang ER, Joseph L, Le Comte M, Fortin PR (2003) Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies. Thromb Haemost 90(1):108–115CrossRefPubMedPubMedCentral Neville C, Rauch J, Kassis J, Chang ER, Joseph L, Le Comte M, Fortin PR (2003) Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies. Thromb Haemost 90(1):108–115CrossRefPubMedPubMedCentral
24.
go back to reference Bramham K, Hunt BJ, Germain S, Calatayud I, Khamashta M, Bewley S, Nelson-Piercy C (2010) Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus 19:58–64CrossRefPubMed Bramham K, Hunt BJ, Germain S, Calatayud I, Khamashta M, Bewley S, Nelson-Piercy C (2010) Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus 19:58–64CrossRefPubMed
25.
go back to reference Mayer-Pickel K, Eberhard K, Lang U, Cervar-Zivkovic M (2017) Pregnancy outcome in women with obstetric and thrombotic antiphospholipid syndrome—a retrospective analysis and a review of additional treatment in pregnancy. Clin Rev Allergy Immunol 53:54–67CrossRefPubMed Mayer-Pickel K, Eberhard K, Lang U, Cervar-Zivkovic M (2017) Pregnancy outcome in women with obstetric and thrombotic antiphospholipid syndrome—a retrospective analysis and a review of additional treatment in pregnancy. Clin Rev Allergy Immunol 53:54–67CrossRefPubMed
26.
go back to reference Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD (2001) High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum 44:1466–1467CrossRefPubMed Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD (2001) High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum 44:1466–1467CrossRefPubMed
27.
go back to reference Drozidnsky G, Hadar E, Shmueli A, Gabbay-Benziv R, Shiber S (2017) Obstetric antiphospholipid syndrome and long term arterial thrombosis risk. J Thromb Thrombolysis 44:1–5CrossRef Drozidnsky G, Hadar E, Shmueli A, Gabbay-Benziv R, Shiber S (2017) Obstetric antiphospholipid syndrome and long term arterial thrombosis risk. J Thromb Thrombolysis 44:1–5CrossRef
28.
go back to reference Lefèvre G, Lambert M, Bacri J-L, Dubucquoi S, Quemeneur T, Caron C, Launay D, Houfflin-Debarge V, Hachulla E, Kyndt X, Subtil D, Hatron P-Y (2011) Thrombotic events during long-term follow-up of obstetric antiphospholipid syndrome patients. Lupus 20:861–865CrossRefPubMed Lefèvre G, Lambert M, Bacri J-L, Dubucquoi S, Quemeneur T, Caron C, Launay D, Houfflin-Debarge V, Hachulla E, Kyndt X, Subtil D, Hatron P-Y (2011) Thrombotic events during long-term follow-up of obstetric antiphospholipid syndrome patients. Lupus 20:861–865CrossRefPubMed
29.
go back to reference Shi H, Zheng H, Yin Y-F, Hu Q-Y, Teng J-L, Sun Y, Liu H-L, Cheng X-B, Ye J-N, Su Y-T, Wu X-Y, Zhou J-F, Norman GL, Gong H-Y, Shi X-M, Peng Y-B, Wang X-F, Yang C-D (2017) Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome. Clin Chem Lab Med 56:614–624CrossRef Shi H, Zheng H, Yin Y-F, Hu Q-Y, Teng J-L, Sun Y, Liu H-L, Cheng X-B, Ye J-N, Su Y-T, Wu X-Y, Zhou J-F, Norman GL, Gong H-Y, Shi X-M, Peng Y-B, Wang X-F, Yang C-D (2017) Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome. Clin Chem Lab Med 56:614–624CrossRef
30.
go back to reference Chaturvedi S, McCrae KR (2017) Clinical risk assessment in the antiphospholipid syndrome: current landscape and emerging biomarkers. Curr Rheumatol Rep 19:43CrossRefPubMed Chaturvedi S, McCrae KR (2017) Clinical risk assessment in the antiphospholipid syndrome: current landscape and emerging biomarkers. Curr Rheumatol Rep 19:43CrossRefPubMed
31.
go back to reference Sugiura-Ogasawara M, Omae Y, Kawashima M, Toyo-Oka L, Khor S-S, Sawai H, Horita T, Atsumi T, Murashima A, Fujita D, Fujita T, Morimoto S, Morishita E, Katsuragi S, Kitaori T, Katano K, Ozaki Y, Tokunaga K (2017) The first genome-wide association study identifying new susceptibility loci for obstetric antiphospholipid syndrome. J Hum Genet 62:831–838CrossRefPubMed Sugiura-Ogasawara M, Omae Y, Kawashima M, Toyo-Oka L, Khor S-S, Sawai H, Horita T, Atsumi T, Murashima A, Fujita D, Fujita T, Morimoto S, Morishita E, Katsuragi S, Kitaori T, Katano K, Ozaki Y, Tokunaga K (2017) The first genome-wide association study identifying new susceptibility loci for obstetric antiphospholipid syndrome. J Hum Genet 62:831–838CrossRefPubMed
Metadata
Title
Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome
Authors
Amihai Rottenstreich
Ariela Arad
Hadas Terespolsky
Uriel Elchalal
Hagai Amsalm
Batia Roth
Yosef Kalish
Publication date
01-08-2018
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 2/2018
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-018-1672-8

Other articles of this Issue 2/2018

Journal of Thrombosis and Thrombolysis 2/2018 Go to the issue