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Hamostaseologie 2019; 39(02): 203-207
DOI: 10.1055/s-0038-1673414
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Antiphospholipid Antibodies in a General Obstetric Population: Clinical Impact on Pregnancy Outcome and Relationship with the M2 Haplotype in the Annexin A5 (ANXA5) Gene

Michela Villani
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
Donatella Colaizzo
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
Pasquale Martinelli
2   Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
,
Filomena Cappucci
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
Lucia Fischetti
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
Giuseppe M. Maruotti
2   Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
,
Mariano Intrieri
3   Department of Medicine and Health Sciences “Vincenzo Tiberio,” University of Molise, Campobasso, Italy
,
Luigi Greco
4   Department of Pediatrics, University of Naples Federico II, Naples, Italy
,
Elena Chinni
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
Giovanni L. Tiscia
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
Maurizio Margaglione
5   Department of Medical Genetics, University of Foggia, Foggia, Italy
,
Elvira Grandone
1   Atherosclerosis and Thrombosis Unit, I.R.C.C.S. “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (Foggia), Italy
,
on behalf of PRENACEL Study Group › Author Affiliations
Further Information

Publication History

13 March 2018

13 August 2018

Publication Date:
10 October 2018 (online)

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Abstract

Antiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in the Annexin A5 gene have been shown to have a higher susceptibility to develop aPL antibodies. In a general obstetric population, we prospectively evaluated the possible relationship between: (1) aPL antibodies and M2 haplotype; and (2) aPL antibodies and/or M2 haplotype and obstetric outcomes. From a cohort of 3,097 consecutive pregnant women, 1,286 samples were analysed for the presence of both anti-cardiolipin and anti-human β2-glycoprotein I antibodies; samples with available DNA (n = 606) were also investigated for the M2 haplotype. Overall, 41/1,286 (3.2%) women showed the presence of aPL antibodies. Among them, 2 (4.8%) experienced a pregnancy loss and 38 (92.7%) gave birth to live-born babies (p-value = non-significant vs. those without aPL antibodies). M2 haplotype was identified in 140 (23.1%) out of 606 women with DNA available: 3/140 (2.1%) M2 carriers and 17/466 (3.6%) non-carriers tested positive for aPL antibodies, respectively (p-value = non-significant). In total, 15/150 (10%) M2 and/or aPL antibody carriers, and 38/445 (8.5%) non-aPL antibody and/or M2 carriers suffered from obstetric complications, respectively (p-value = non-significant). No relationship between aPL antibodies and M2 haplotype was found. Furthermore, neither aPL antibodies nor the M2 haplotype is associated with obstetric complications.

Zusammenfassung

Antiphospholipid (aPL) -Antikörper sind anerkannte Risikofaktoren für ungünstige geburtshilfliche Ergebnisse. Kürzlich wurde gezeigt dass Träger des M2-Haplotyps im Annexin-A5-Gen eine höhere Anfälligkeit für die Entwicklung von aPL-Antikörpern aufweisen. In einer allgemeinen geburtshilflichen Population untersuchten wir prospektiv die mögliche Beziehung zwischen: (1) aPL-Antikörpern und M2-Haplotyp; und (2) aPL-Antikörper und / oder M2-Haplotyp und geburtshilfliche Ergebnisse. Aus einer Kohorte von 3.097 konsekutiven Schwangeren wurden 1.286 Proben auf das Vorhandensein von sowohl Anti-Cardiolipin- als auch Anti-Human-β2-Glykoprotein-I-Antikörpern analysiert; Proben mit verfügbarer DNA (n = 606) wurden ebenfalls auf den M2-Haplotyp untersucht. Insgesamt zeigten 41 / 1.286 (32%) Frauen das Vorhandensein von aPL-Antikörpern. Unter ihnen hatten 2 (48%) einen Schwangerschaftsverlust und 38 (927%) gaben lebendgeborene Babys zur Welt (p-Wert = nicht-signifikant gegenüber denen ohne aPL-Antikörper). Der M2-Haplotyp wurde bei 140 (231%) von 606 Frauen mit verfügbarer DNA identifiziert: 3/140 (21%) M2-Träger und 17/466 (36%) Nichtträger die positiv auf aPL-Antikörper getestet wurden (p-Wert = nicht signifikant). Insgesamt litten 15/150 (10%) M2- und / oder aPL-Antikörperträger und 38/445 (85%) Nicht-aPL-Antikörper und / oder M2-Träger an geburtshilflichen Komplikationen (p-Wert = nicht signifikant). Es wurde keine Beziehung zwischen aPL-Antikörpern und M2-Haplotypen gefunden. Darüber hinaus sind weder aPL-Antikörper noch der M2-Haplotyp mit geburtshilflichen Komplikationen assoziiert.

Keywords

annexins - antiphospholipid antibodies - pregnancy

Schlüsselwörter

Annexine - Antiphospholipid-Antikörper - Schwangerschaft
 

  • References

  • 1 Kutteh WH, Hinote CD. Antiphospholipid antibody syndrome. Obstet Gynecol Clin North Am 2014; 41 (01) 113-132
    CrossrefPubMedGoogle Scholar
  • 2 Ruffatti A, Tonello M, Cavazzana A, Bagatella P, Pengo V. Laboratory classification categories and pregnancy outcome in patients with primary antiphospholipid syndrome prescribed antithrombotic therapy. Thromb Res 2009; 123 (03) 482-487
    CrossrefPubMedGoogle Scholar
  • 3 Biggioggero M, Meroni PL. The geoepidemiology of the antiphospholipid antibody syndrome. Autoimmun Rev 2010; 9 (05) A299-A304
    CrossrefPubMedGoogle Scholar
  • 4 Bogdanova N, Horst J, Chlystun M. , et al. A common haplotype of the annexin A5 (ANXA5) gene promoter is associated with recurrent pregnancy loss. Hum Mol Genet 2007; 16 (05) 573-578
    CrossrefPubMedGoogle Scholar
  • 5 Bouter A, Gounou C, Bérat R. , et al. Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair. Nat Commun 2011; 2: 270
    CrossrefPubMedGoogle Scholar
  • 6 Chinni E, Tiscia GL, Colaizzo D, Vergura P, Margaglione M, Grandone E. Annexin V expression in human placenta is influenced by the carriership of the common haplotype M2. Fertil Steril 2009; 91 (03) 940-942
    CrossrefPubMedGoogle Scholar
  • 7 Tiscia G, Colaizzo D, Chinni E. , et al. Haplotype M2 in the annexin A5 (ANXA5) gene and the occurrence of obstetric complications. Thromb Haemost 2009; 102 (02) 309-313
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Tiscia G, Colaizzo D, Favuzzi G. , et al. The M2 haplotype in the ANXA5 gene is an independent risk factor for idiopathic small-for-gestational age newborns. Mol Hum Reprod 2012; 18 (10) 510-513
    CrossrefPubMedGoogle Scholar
  • 9 Grandone E, Tiscia G, Colaizzo D. , et al. Role of the M2 haplotype within the annexin A5 gene in the occurrence of pregnancy-related venous thromboembolism. Am J Obstet Gynecol 2010; 203 (05) 461.e1-461.e5
    CrossrefPubMedGoogle Scholar
  • 10 Dahm AE, Tiscia G, Holmgren A. , et al. Genetic variations in the annexin A5 gene and the risk of pregnancy-related venous thrombosis. J Thromb Haemost 2015; 13 (03) 409-413
    CrossrefPubMedGoogle Scholar
  • 11 Bogdanova N, Baleva M, Kremensky I, Markoff A. The annexin A5 protective shield model revisited: inherited carriage of the M2/ANXA5 haplotype in placenta as a predisposing factor for the development of obstetric antiphospholipid antibodies. Lupus 2012; 21 (07) 796-798
    CrossrefPubMedGoogle Scholar
  • 12 Hiddink L, de Laat B, Derksen RH, de Groot PG, van Heerde WL. Annexin A5 haplotypes in the antiphospholipid syndrome. Thromb Res 2015; 135 (02) 417-419
    CrossrefPubMedGoogle Scholar
  • 13 Grandone E, Colaizzo D, Tiscia G. , et al; PRENACEL Study Group. Impact of common thrombophilias and JAK2 V617F on pregnancy outcomes in unselected Italian women. J Thromb Haemost 2011; 9 (03) 496-501
    CrossrefPubMedGoogle Scholar
  • 14 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 (02) 295-306
    CrossrefPubMedGoogle Scholar
  • 15 Infante-Rivard C, David M, Gauthier R, Rivard GE. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss. A case-control study. N Engl J Med 1991; 325 (15) 1063-1066
    CrossrefPubMedGoogle Scholar
  • 16 Amengual O, Fujita D, Ota E. , et al. Primary prophylaxis to prevent obstetric complications in asymptomatic women with antiphospholipid antibodies: a systematic review. Lupus 2015; 24 (11) 1135-1142
    CrossrefPubMedGoogle Scholar