Skip to main content

Advertisement

SpringerLink
Log in

Pediatric APS: State of the Art

  • Antiphospholipid Syndrome (S Zuily, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of this report is to review recent research findings on APS in children and neonates.

Recent Findings

European evidence-based recommendations for diagnosis and treatment of pediatric APS has recently been published by the SHARE Initiative. Recent studies have shown a high prevalence of non-thrombotic manifestations in children with aPL, domains 4/5 specificity of ‘innocent’ anti-β2GPI antibodies in infants, and a higher risk for developmental delays and learning disabilities, hence, the need for neurodevelopmental monitoring in children born to mothers with APS. An International effort on creating a new diagnostic criteria for APS is underway.

Summary

Pediatric APS is a rare disease with significant differences from the APS in adults. Majority of the children with persistently positive aPL do not develop thrombotic events; however, relatively higher proportion of thrombosis in children is related to aPL positivity compared to adults; this may partly be due to the absence of common pro-thrombotic “second-hit” risk factors of adults such as atherosclerosis and cigarette smoking. Diagnosis of APS in children may be delayed or missed when adult APS criteria are used, because in pediatric APS, non-thrombotic clinical manifestations such as thrombocytopenia, hemolytic anemia, and neurological disorders such as migraine, epilepsy, and chorea may precede thrombotic manifestations. Around 20% of the children initially diagnosed with primary APS eventually develop SLE. Neonatal APS is rare; however, the offspring of mothers with APS are at a higher risk for developmental delays and learning disabilities; prematurity and IUGR may increase this risk. Regular assessment of neurodevelopmental status of these children should be performed. Thrombosis is a rare event in the offspring of mothers with APS; anticoagulation of such infants is not recommended. An international effort to create a new diagnostic criteria for APS is underway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 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(2):295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.x.

    Article  CAS  Google Scholar 

  2. Wulffraat NM, Vastert B, Consortium S. Time to share. Pediatr Rheumatol Online J. 2013;11(1):5. https://doi.org/10.1186/1546-0096-11-5.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Groot N, de Graeff N, Avcin T, Bader-Meunier B, Dolezalova P, Feldman B, et al. European evidence-based recommendations for diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative. Ann Rheum Dis. 2017;76(10):1637–41. https://doi.org/10.1136/annrheumdis-2016-211001Recent, international evidence-based recommendations based on EULAR operating procedures, to facilitate improvement and uniformity of care.

    Article  CAS  Google Scholar 

  4. Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999;42(7):1309–11. https://doi.org/10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F.

    Article  CAS  Google Scholar 

  5. Avcin T, Cimaz R, Meroni PL. Do we need an international consensus statement on classification criteria for the antiphospholipid syndrome in the paediatric population? Lupus. 2001;10(12):897–8. https://doi.org/10.1191/096120301701548427.

    Article  CAS  PubMed  Google Scholar 

  6. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019–27.

    Article  Google Scholar 

  7. Angelini L, Zibordi F, Zorzi G, Nardocci N, Caporali R, Ravelli A, et al. Neurological disorders, other than stroke, associated with antiphospholipid antibodies in childhood. Neuropediatrics. 1996;27(3):149–53. https://doi.org/10.1055/s-2007-973766.

    Article  CAS  PubMed  Google Scholar 

  8. Avcin T, Cimaz R, Silverman ED, Cervera R, Gattorno M, Garay S, et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics. 2008;122(5):e1100–7. https://doi.org/10.1542/peds.2008-1209Most comprehensive descriptive characteristics of pediatric APS from an international registry.

    Article  PubMed  Google Scholar 

  9. Avcin T, Cimaz R, Meroni PL. Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations. Lupus. 2002;11(1):4–10. https://doi.org/10.1191/0961203302lu146rr.

    Article  CAS  PubMed  Google Scholar 

  10. 15th Paediatric Rheumatology European Society (PreS) Congress London, UK. 14–17 September 2008. Abstracts. Pediatric rheumatology online journal. 2008;6 Suppl 1:P1-S34.

  11. Nuss R, Hays T, Manco-Johnson M. Childhood thrombosis. Pediatrics. 1995;96(2 Pt 1):291–4.

    CAS  PubMed  Google Scholar 

  12. Zamora-Ustaran A, Escarcega-Alarcon RO, Garcia-Carrasco M, Faugier E, Mendieta-Zeron S, Mendoza-Pinto C, et al. Antiphospholipid syndrome in Mexican children. Isr Med Assoc J. 2012;14(5):286–9.

    PubMed  Google Scholar 

  13. Ma J, Song H, Wei M, He Y. Clinical characteristics and thrombosis outcomes of paediatric antiphospholipid syndrome: analysis of 58 patients. Clin Rheumatol. 2018;37(5):1295–303. https://doi.org/10.1007/s10067-017-3776-5.

    Article  PubMed  Google Scholar 

  14. Avcin T, Ambrozic A, Kuhar M, Kveder T, Rozman B. Anticardiolipin and anti-beta(2) glycoprotein I antibodies in sera of 61 apparently healthy children at regular preventive visits. Rheumatology. 2001;40(5):565–73.

    Article  CAS  Google Scholar 

  15. Aguiar CL, Soybilgic A, Avcin T, Myones BL. Pediatric antiphospholipid syndrome. Curr Rheumatol Rep. 2015;17(4):27. https://doi.org/10.1007/s11926-015-0504-5.

    Article  CAS  PubMed  Google Scholar 

  16. Male C, Lechner K, Eichinger S, Kyrle PA, Kapiotis S, Wank H, et al. Clinical significance of lupus anticoagulants in children. J Pediatr. 1999;134(2):199–205.

    Article  CAS  Google Scholar 

  17. Burk CD, Miller L, Handler SD, Cohen AR. Preoperative history and coagulation screening in children undergoing tonsillectomy. Pediatrics. 1992;89(4 Pt 2):691–5.

    CAS  PubMed  Google Scholar 

  18. Gharavi AE, Pierangeli SS. Origin of antiphospholipid antibodies: induction of aPL by viral peptides. Lupus. 1998;7(Suppl 2):S52–4.

    Article  CAS  Google Scholar 

  19. Avcin T, Toplak N. Antiphospholipid antibodies in response to infection. Curr Rheumatol Rep. 2007;9(3):212–8.

    Article  CAS  Google Scholar 

  20. Mizumoto H, Maihara T, Hiejima E, Shiota M, Hata A, Seto S, et al. Transient antiphospholipid antibodies associated with acute infections in children: a report of three cases and a review of the literature. Eur J Pediatr. 2006;165(7):484–8. https://doi.org/10.1007/s00431-006-0117-0.

    Article  CAS  PubMed  Google Scholar 

  21. Mormile R, D'Alterio V, Treccagnoli G, Sorrentino P. Henoch-Schonlein purpura with antiphospholipid antibodies after influenza vaccination: how fearful is it in children? Vaccine. 2004;23(5):567–8. https://doi.org/10.1016/j.vaccine.2004.07.029.

    Article  PubMed  Google Scholar 

  22. Bizjak M, Bruck O, Kanduc D, Praprotnik S, Shoenfeld Y. Vaccinations and secondary immune thrombocytopenia with antiphospholipid antibodies by human papillomavirus vaccine. Semin Hematol. 2016;53(Suppl 1):S48–50. https://doi.org/10.1053/j.seminhematol.2016.04.014.

    Article  PubMed  Google Scholar 

  23. Katzav A, Kivity S, Blank M, Shoenfeld Y, Chapman J. Adjuvant immunization induces high levels of pathogenic antiphospholipid antibodies in genetically prone mice: another facet of the ASIA syndrome. Lupus. 2012;21(2):210–6. https://doi.org/10.1177/0961203311429550.

    Article  CAS  PubMed  Google Scholar 

  24. Cruz-Tapias P, Blank M, Anaya JM, Shoenfeld Y. Infections and vaccines in the etiology of antiphospholipid syndrome. Curr Opin Rheumatol. 2012;24(4):389–93. https://doi.org/10.1097/BOR.0b013e32835448b8.

    Article  CAS  PubMed  Google Scholar 

  25. Angelini L, Ravelli A, Caporali R, Rumi V, Nardocci N, Martini A. High prevalence of antiphospholipid antibodies in children with idiopathic cerebral ischemia. Pediatrics. 1994;94(4 Pt 1):500–3.

    CAS  PubMed  Google Scholar 

  26. Manco-Johnson MJ, Nuss R. Lupus anticoagulant in children with thrombosis. Am J Hematol. 1995;48(4):240–3.

    Article  CAS  Google Scholar 

  27. Kenet G, Aronis S, Berkun Y, Bonduel M, Chan A, Goldenberg NA, et al. Impact of persistent antiphospholipid antibodies on risk of incident symptomatic thromboembolism in children: a systematic review and meta-analysis. Semin Thromb Hemost. 2011;37(7):802–9. https://doi.org/10.1055/s-0031-1297171A meta-analysis describing the impact of antiphospholipid antibodies on the risk of thrombotic events in children.

    Article  CAS  PubMed  Google Scholar 

  28. Pengo V, Biasiolo A, Gresele P, Marongiu F, Erba N, Veschi F, et al. Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost. 2007;5(5):925–30. https://doi.org/10.1111/j.1538-7836.2007.02454.x.

    Article  CAS  PubMed  Google Scholar 

  29. Nakashima MO, Rogers HJ. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood Res. 2014;49(2):85–94. https://doi.org/10.5045/br.2014.49.2.85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Guerin J, Casey E, Feighery C, Jackson J. Anti-Beta 2-glycoprotein I antibody isotype and IgG subclass in antiphospholipid syndrome patients. Autoimmunity. 1999;31(2):109–16.

    Article  CAS  Google Scholar 

  31. Male C, Foulon D, Hoogendoorn H, Vegh P, Silverman E, David M, et al. Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus. Blood. 2005;106(13):4152–8. https://doi.org/10.1182/blood-2005-05-2048.

    Article  CAS  PubMed  Google Scholar 

  32. Tavil B, Ozyurek E, Gumruk F, Cetin M, Gurgey A. Antiphospholipid antibodies in Turkish children with thrombosis. Blood Coagul Fibrinolysis. 2007;18(4):347–52. https://doi.org/10.1097/MBC.0b013e32809cc95a.

    Article  CAS  PubMed  Google Scholar 

  33. Bonduel M, Hepner M, Sciuccati G, Pieroni G, Feliu-Torres A, Mardaraz C, et al. Factor V Leiden and prothrombin gene G20210A mutation in children with venous thromboembolism. Thromb Haemost. 2002;87(6):972–7.

    Article  CAS  Google Scholar 

  34. Hudson M, Herr AL, Rauch J, Neville C, Chang E, Ibrahim R, et al. The presence of multiple prothrombotic risk factors is associated with a higher risk of thrombosis in individuals with anticardiolipin antibodies. J Rheumatol. 2003;30(11):2385–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kontiainen S, Miettinen A, Seppala I, Verkasalo M, Maenpaa J. Antiphospholipid antibodies in children. Acta Paediatr. 1996;85(5):614–5.

    Article  CAS  Google Scholar 

  36. Andreoli L, Nalli C, Motta M, Norman GL, Shums Z, Encabo S, et al. Anti-beta(2)-glycoprotein I IgG antibodies from 1-year-old healthy children born to mothers with systemic autoimmune diseases preferentially target domain 4/5: might it be the reason for their 'innocent' profile? Ann Rheum Dis. 2011;70(2):380–3. https://doi.org/10.1136/ard.2010.137281.

    Article  CAS  PubMed  Google Scholar 

  37. Ambrozic A, Avicin T, Ichikawa K, Kveder T, Matsuura E, Hojnik M, et al. Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis. Int Immunol. 2002;14(7):823–30. https://doi.org/10.1093/intimm/dxf043.

    Article  CAS  PubMed  Google Scholar 

  38. Artenjak A, Locatelli I, Brelih H, Simonic DM, Ulcova-Gallova Z, Swadzba J, et al. Immunoreactivity and avidity of IgG anti-beta2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of beta2-glycoprotein I. Immunol Res. 2015;61(1–2):35–44. https://doi.org/10.1007/s12026-014-8578-0.

    Article  CAS  PubMed  Google Scholar 

  39. Cucnik S, Kveder T, Artenjak A, Ulcova Gallova Z, Swadzba J, Musial J, et al. Avidity of anti-beta2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Lupus. 2012;21(7):764–5. https://doi.org/10.1177/0961203312440057.

    Article  CAS  PubMed  Google Scholar 

  40. Cucnik S, Kveder T, Ulcova-Gallova Z, Swadzba J, Musial J, Valesini G, et al. The avidity of anti-beta2-glycoprotein I antibodies in patients with or without antiphospholipid syndrome: a collaborative study in the frame of the European forum on antiphospholipid antibodies. Lupus. 2011;20(11):1166–71. https://doi.org/10.1177/0961203311406308.

    Article  CAS  PubMed  Google Scholar 

  41. Moulis G, Delavigne K, Huguet F, Fortenfant F, Beyne-Rauzy O, Adoue D. Antiphospholipid antibodies and the risk of thrombosis: a comparative survey between chronic immune thrombocytopenia and primary antiphospholipid syndrome. Rev Med Interne. 2011;32(12):724–9. https://doi.org/10.1016/j.revmed.2011.07.014.

    Article  CAS  PubMed  Google Scholar 

  42. Sakai M, Shirahata A, Akatsuka J, Fujisawa K, Ohkawa H, Konishi S, et al. Antiphospholipid antibodies in children with idiopathic thrombocytopenic purpura. [Rinsho ketsueki]. Jpn J Clin Hematol. 2002;43(9):821–7.

    Google Scholar 

  43. Frison L, Lombardi A, Caputo I, Semenzato G, Fabris F, Vianello F. Relevance of antiphospholipid antibody profile in the clinical outcome of ITP: a single-centre study. Hematology. 2019;24(1):134–8. https://doi.org/10.1080/10245332.2018.1532649.

    Article  CAS  PubMed  Google Scholar 

  44. Avcin T, Jazbec J, Kuhar M, Zupancic M, Rozman B. Evans syndrome associated with antiphospholipid antibodies. J Pediatr Hematol Oncol. 2003;25(9):755–6.

    Article  Google Scholar 

  45. Anurathapan U, Sasanakul W, Sirachainan N, Kasemkosolsri C, Jaovisidha S, Chuansumrit A. Acquired hypoprothrombinemia inducing bleeding in a girl with transient antiphospholipid antibody: case report. J Med Assoc Thailand = Chotmaihet thangphaet. 2012;95(2):282–7.

    Google Scholar 

  46. Galland J, Mohamed S, Revuz S, de Maistre E, de Laat B, Marie PY, et al. Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies. Blood Coagul Fibrinolysis. 2016;27(5):580–2. https://doi.org/10.1097/MBC.0000000000000545.

    Article  PubMed  Google Scholar 

  47. Sellami M, Elloumi M, Fourati H, Ayadi N, Baklouti S. Combined hypoprothrombinemia-antiphospholipid syndrome in a patient suffering from lupus. Presse Med. 2004;33(6):391.

    Article  Google Scholar 

  48. Cetin Gedik K, Siddique S, Aguiar CL. Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome - report of three cases and review of the literature. Lupus. 2018;27(7):1190–7. https://doi.org/10.1177/0961203317751853.

    Article  CAS  PubMed  Google Scholar 

  49. Cimaz R, Romeo A, Scarano A, Avcin T, Viri M, Veggiotti P, et al. Prevalence of anti-cardiolipin, anti-beta2 glycoprotein I, and anti-prothrombin antibodies in young patients with epilepsy. Epilepsia. 2002;43(1):52–9.

    Article  CAS  Google Scholar 

  50. Eriksson K, Peltola J, Keranen T, Haapala AM, Koivikko M. High prevalence of antiphospholipid antibodies in children with epilepsy: a controlled study of 50 cases. Epilepsy Res. 2001;46(2):129–37.

    Article  CAS  Google Scholar 

  51. Islam MA, Alam F, Cavestro C, Calcii C, Sasongko TH, Levy RA, et al. Antiphospholipid antibodies in epilepsy: a systematic review and meta-analysis. Autoimmun Rev. 2018;17(8):755–67. https://doi.org/10.1016/j.autrev.2018.01.025.

    Article  CAS  PubMed  Google Scholar 

  52. Noureldine MH, Harifi G, Berjawi A, Haydar AA, Nader M, Elnawar R, et al. Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies? Lupus. 2016;25(13):1397–411. https://doi.org/10.1177/0961203316651747.

    Article  CAS  PubMed  Google Scholar 

  53. Islam MA, Alam F, Wong KK. Comorbid association of antiphospholipid antibodies and migraine: a systematic review and meta-analysis. Autoimmun Rev. 2017;16(5):512–22. https://doi.org/10.1016/j.autrev.2017.03.005.

    Article  PubMed  Google Scholar 

  54. Kopytek M, Natorska J, Undas A. Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are associated with Raynaud phenomenon and migraine in primary thrombotic antiphospholipid syndrome. Lupus. 2018;27(5):812–9. https://doi.org/10.1177/0961203317751644.

    Article  CAS  PubMed  Google Scholar 

  55. Noureldine MHA, Haydar AA, Berjawi A, Elnawar R, Sweid A, Khamashta MA, et al. Antiphospholipid syndrome (APS) revisited: would migraine headaches be included in future classification criteria? Immunol Res. 2017;65(1):230–41. https://doi.org/10.1007/s12026-016-8831-9.

    Article  CAS  PubMed  Google Scholar 

  56. Sanna G, Bertolaccini ML, Hughes GR. Hughes syndrome, the antiphospholipid syndrome: a new chapter in neurology. Ann N Y Acad Sci. 2005;1051:465–86. https://doi.org/10.1196/annals.1361.088.

    Article  CAS  PubMed  Google Scholar 

  57. Tufano A, Di Minno MND, Guida A, Lembo M, Di Minno G, Galderisi M. Cardiac manifestations of antiphospholipid syndrome: clinical presentation, role of cardiac imaging, and treatment strategies. Semin Thromb Hemost. 2019;45(5):468–77. https://doi.org/10.1055/s-0039-1692702.

    Article  CAS  PubMed  Google Scholar 

  58. Clauss SB, Manco-Johnson MJ, Quivers E, Takemoto C, Spevak PJ. Primary antiphospholipid antibody syndrome and cardiac involvement in a child. Pediatr Cardiol. 2003;24(3):292–4. https://doi.org/10.1007/s00246-002-0273-6.

    Article  CAS  PubMed  Google Scholar 

  59. Bakshi M, Khemani C, Vishwanathan V, Anand RK, Khubchandani RP. Mycoplasma pneumonia with antiphospholipid antibodies and a cardiac thrombus. Lupus. 2006;15(2):105–6. https://doi.org/10.1191/0961203306lu2258cr.

    Article  CAS  PubMed  Google Scholar 

  60. Abisror N, Mekinian A, Lachassinne E, Nicaise-Roland P, De Pontual L, Chollet-Martin S, et al. Autism spectrum disorders in babies born to mothers with antiphospholipid syndrome. Semin Arthritis Rheum. 2013;43(3):348–51. https://doi.org/10.1016/j.semarthrit.2013.07.001.

    Article  CAS  PubMed  Google Scholar 

  61. Lageix F, Nicaise-Roland P, Houlier M, Zylberberg P, Dubrel M, Heulin M, et al. Association between the presence of antiphospholipid antibodies and the occurrence of autism spectrum disorder in childhood. Arch Pediatr. 2015;22(11):1140–6. https://doi.org/10.1016/j.arcped.2015.08.007.

    Article  CAS  PubMed  Google Scholar 

  62. Careaga M, Hansen RL, Hertz-Piccotto I, Van de Water J, Ashwood P. Increased anti-phospholipid antibodies in autism spectrum disorders. Mediat Inflamm. 2013;2013:935608. https://doi.org/10.1155/2013/935608.

    Article  CAS  Google Scholar 

  63. Orsino A, Schneider R, DeVeber G, Grant R, Massicotte P, Canning P, et al. Childhood acute myelomonocytic leukemia (AML-M4) presenting as catastrophic antiphospholipid antibody syndrome. J Pediatr Hematol Oncol. 2004;26(5):327–30.

    Article  Google Scholar 

  64. Miesbach W, Asherson RA, Cervera R, Shoenfeld Y, Gomez Puerta J, Bucciarelli S, et al. The catastrophic antiphospholipid (Asherson's) syndrome and malignancies. Autoimmun Rev. 2006;6(2):94–7. https://doi.org/10.1016/j.autrev.2006.06.012.

    Article  CAS  PubMed  Google Scholar 

  65. Berkun Y, Padeh S, Barash J, Uziel Y, Harel L, Mukamel M, et al. Antiphospholipid syndrome and recurrent thrombosis in children. Arthritis Rheum. 2006;55(6):850–5. https://doi.org/10.1002/art.22360.

    Article  CAS  PubMed  Google Scholar 

  66. Campos LM, Kiss MH, D'Amico EA, Silva CA. Antiphospholipid antibodies and antiphospholipid syndrome in 57 children and adolescents with systemic lupus erythematosus. Lupus. 2003;12(11):820–6. https://doi.org/10.1191/0961203303lu471oa.

    Article  CAS  PubMed  Google Scholar 

  67. Ahluwalia J, Singh S, Garewal G. Antiphospholipid antibodies in children with systemic lupus erythematosus: a prospective study in northern India. Rheumatol Int. 2005;25(7):530–5. https://doi.org/10.1007/s00296-004-0501-x.

    Article  CAS  PubMed  Google Scholar 

  68. Seaman DE, Londino AV Jr, Kwoh CK, Medsger TA Jr, Manzi S. Antiphospholipid antibodies in pediatric systemic lupus erythematosus. Pediatrics. 1995;96(6):1040–5.

    CAS  PubMed  Google Scholar 

  69. Avcin T, Silverman ED. Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome. Lupus. 2007;16(8):627–33. https://doi.org/10.1177/0961203307079036.

    Article  CAS  PubMed  Google Scholar 

  70. Molta C, Meyer O, Dosquet C, Montes de Oca M, Babron MC, Danon F, et al. Childhood-onset systemic lupus erythematosus: antiphospholipid antibodies in 37 patients and their first-degree relatives. Pediatrics. 1993;92(6):849–53.

    CAS  PubMed  Google Scholar 

  71. Gattorno M, Buoncompagni A, Molinari AC, Barbano GC, Morreale G, Stalla F, et al. Antiphospholipid antibodies in paediatric systemic lupus erythematosus, juvenile chronic arthritis and overlap syndromes: SLE patients with both lupus anticoagulant and high-titre anticardiolipin antibodies are at risk for clinical manifestations related to the antiphospholipid syndrome. Br J Rheumatol. 1995;34(9):873–81.

    Article  CAS  Google Scholar 

  72. Berube C, Mitchell L, Silverman E, David M, Saint Cyr C, Laxer R, et al. The relationship of antiphospholipid antibodies to thromboembolic events in pediatric patients with systemic lupus erythematosus: a cross-sectional study. Pediatr Res. 1998;44(3):351–6. https://doi.org/10.1203/00006450-199809000-00014.

    Article  CAS  PubMed  Google Scholar 

  73. Gedalia A, Molina JF, Garcia CO, Doggett S, Espinoza LR, Gharavi AE. Anticardiolipin antibodies in childhood rheumatic disorders. Lupus. 1998;7(8):551–3. https://doi.org/10.1191/096120398678920659.

    Article  CAS  PubMed  Google Scholar 

  74. Ravelli A, Caporali R, Di Fuccia G, Zonta L, Montecucco C, Martini A. Anticardiolipin antibodies in pediatric systemic lupus erythematosus. Arch Pediatr Adolesc Med. 1994;148(4):398–402.

    Article  CAS  Google Scholar 

  75. Avcin T, Benseler SM, Tyrrell PN, Cucnik S, Silverman ED. A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus. Arthritis Rheum. 2008;59(2):206–13. https://doi.org/10.1002/art.23334.

    Article  PubMed  Google Scholar 

  76. Ahluwalia J, Singh S, Naseem S, Suri D, Rawat A, Gupta A, et al. Antiphospholipid antibodies in children with systemic lupus erythematosus: a long-term clinical and laboratory follow-up status study from northwest India. Rheumatol Int. 2014;34(5):669–73. https://doi.org/10.1007/s00296-013-2736-x.

    Article  CAS  PubMed  Google Scholar 

  77. Al-Mayouf SM, AlSaleem A, Al-Hussain T, Al Sonbul A, AlMana H. The impact of antiphospholipid antibodies in children with lupus nephritis. Int J Pediatr Adolesc Med. 2015;2(3–4):147–51. https://doi.org/10.1016/j.ijpam.2015.08.002.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Southwood TR, Roberts-Thomson PJ, Ahern MJ, Shepherd K, McEvoy R, Ziegler JB, et al. Autoantibodies in patients with juvenile chronic arthritis and their immediate family relatives. Ann Rheum Dis. 1990;49(12):968–72. https://doi.org/10.1136/ard.49.12.968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Caporali R, Ravelli A, De Gennaro F, Neirotti G, Montecucco C, Martini A. Prevalence of anticardiolipin antibodies in juvenile chronic arthritis. Ann Rheum Dis. 1991;50(9):599–601. https://doi.org/10.1136/ard.50.9.599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Caporali R, Ravelli A, Ramenghi B, Montecucco C, Martini A. Antiphospholipid antibody associated thrombosis in juvenile chronic arthritis. Arch Dis Child. 1992;67(11):1384–5. https://doi.org/10.1136/adc.67.11.1384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Andrews A, Hickling P. Thrombosis associated with antiphospholipid antibody in juvenile chronic arthritis. Lupus. 1997;6(6):556–7. https://doi.org/10.1177/096120339700600616.

    Article  CAS  PubMed  Google Scholar 

  82. Diniz RE, Goldenberg J, Andrade LE, Leser PG, Silva NP, Roizenblatt S, et al. Antiphospholipid antibodies in rheumatic fever chorea. J Rheumatol. 1994;21(7):1367–8.

    CAS  PubMed  Google Scholar 

  83. Meglic A, Grosek S, Benedik-Dolnicar M, Avcin T. Atypical haemolytic uremic syndrome complicated by microangiopathic antiphospholipid-associated syndrome. Lupus. 2008;17(9):842–5. https://doi.org/10.1177/0961203308091634.

    Article  CAS  PubMed  Google Scholar 

  84. Souza FH, Levy-Neto M, Shinjo SK. Antiphospholipid syndrome and dermatomyositis/polymyositis: a rare association. Rev Bras Reumatol. 2012;52(4):642–4.

    Article  Google Scholar 

  85. Sherer Y, Livneh A, Levy Y, Shoenfeld Y, Langevitz P. Dermatomyositis and polymyositis associated with the antiphospholipid syndrome-a novel overlap syndrome. Lupus. 2000;9(1):42–6. https://doi.org/10.1177/096120330000900108.

    Article  CAS  PubMed  Google Scholar 

  86. da Silva F, de Carvalho J. Rheumatic fever associated with antiphospholipid syndrome: systematic review. J Immunol Res. 2014;2014:614591. https://doi.org/10.1155/2014/614591.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74(6):1011–8. https://doi.org/10.1136/annrheumdis-2013-204838.

    Article  CAS  PubMed  Google Scholar 

  88. Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med. 2003;349(12):1133–8. https://doi.org/10.1056/NEJMoa035241.

    Article  CAS  PubMed  Google Scholar 

  89. Haley KM. Neonatal venous thromboembolism. Front Pediatr. 2017;5:136. https://doi.org/10.3389/fped.2017.00136.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the full-term infant. Blood. 1987;70(1):165–72.

    Article  CAS  Google Scholar 

  91. Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol/Oncol. 1990;12(1):95–104.

    Article  CAS  Google Scholar 

  92. Thornburg C, Pipe S. Neonatal thromboembolic emergencies. Semin Fetal Neonatal Med. 2006;11(3):198–206. https://doi.org/10.1016/j.siny.2006.01.005.

    Article  PubMed  Google Scholar 

  93. Nowak-Gottl U, Kurnik K, Manner D, Kenet G. Thrombophilia testing in neonates and infants with thrombosis. Semin Fetal Neonatal Med. 2011;16(6):345–8. https://doi.org/10.1016/j.siny.2011.07.005.

    Article  PubMed  Google Scholar 

  94. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988;72(5):1651–7.

    Article  CAS  Google Scholar 

  95. Boffa MC, Lachassinne E, Boinot C, De Carolis S, Rovere-Querini P, Avcin T, et al. European registry of babies born to mothers with antiphospholipid syndrome: a result update. Lupus. 2009;18(10):900–4. https://doi.org/10.1177/0961203309106951.

    Article  PubMed  Google Scholar 

  96. Mekinian A, Lachassinne E, Nicaise-Roland P, Carbillon L, Motta M, Vicaut E, et al. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis. 2013;72(2):217–22. https://doi.org/10.1136/annrheumdis-2011-201167A prospective study describing the long-term outcomes of children born to mothers with APS.

    Article  PubMed  Google Scholar 

  97. Motta M, Chirico G, Rebaioli CB, Faden D, Lojacono A, Allegri F, et al. Anticardiolipin and anti-beta2 glycoprotein I antibodies in infants born to mothers with antiphospholipid antibody-positive autoimmune disease: a follow-up study. Am J Perinatol. 2006;23(4):247–51. https://doi.org/10.1055/s-2006-939533.

    Article  PubMed  Google Scholar 

  98. Patra S, Krishnamurthy S, Seth A, Beri S, Aneja S. Bilateral optic neuritis in pediatric systemic lupus erythematosus with antiphospholipid antibody syndrome. Indian J Pediatr. 2011;78(2):234–6. https://doi.org/10.1007/s12098-010-0228-5.

    Article  PubMed  Google Scholar 

  99. Garty BZ, Ludomirsky A, Danon YL, Peter JB, Douglas SD. Placental transfer of immunoglobulin G subclasses. Clin Diagn Lab Immunol. 1994;1(6):667–9.

    Article  CAS  Google Scholar 

  100. Ruffatti A, Calligaro A, Hoxha A, Trevisanuto D, Ruffatti AT, Gervasi MT, et al. Laboratory and clinical features of pregnant women with antiphospholipid syndrome and neonatal outcome. Arthritis Care Res. 2010;62(3):302–7. https://doi.org/10.1002/acr.20098.

    Article  CAS  Google Scholar 

  101. Boffa MC, Lachassinne E. Infant perinatal thrombosis and antiphospholipid antibodies: a review. Lupus. 2007;16(8):634–41. https://doi.org/10.1177/0961203307079039.

    Article  PubMed  Google Scholar 

  102. Peixoto MV, de Carvalho JF, Rodrigues CE. Clinical, laboratory, and therapeutic analyses of 21 patients with neonatal thrombosis and antiphospholipid antibodies: a literature review. J Immunol Res. 2014;2014:672603. https://doi.org/10.1155/2014/672603.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Jeremic K, Stefanovic A, Dotlic J, Stojnic J, Kadija S, Vilendecic Z, et al. Neonatal outcome in pregnant patients with antiphospholipid syndrome. J Perinat Med. 2015;43(6):761–8. https://doi.org/10.1515/jpm-2014-0118.

    Article  CAS  PubMed  Google Scholar 

  104. Botet F, Romera G, Montagut P, Figueras J, Carmona F, Balasch J. Neonatal outcome in women treated for the antiphospholipid syndrome during pregnancy. J Perinat Med. 1997;25(2):192–6.

    Article  CAS  Google Scholar 

  105. Tabbutt S, Griswold WR, Ogino MT, Mendoza AE, Allen JB, Reznik VM. Multiple thromboses in a premature infant associated with maternal phospholipid antibody syndrome. J Perinatol. 1994;14(1):66–70.

    CAS  PubMed  Google Scholar 

  106. De Carolis MP, Salvi S, Botta A, Cocca C, Garufi C, Lanzone A, et al. Cerebral sinovenous thrombosis in neonatal antiphospholipid syndrome: a new entity? Lupus. 2015;24(3):231–4. https://doi.org/10.1177/0961203314560207.

    Article  PubMed  Google Scholar 

  107. Nacinovich R, Galli J, Bomba M, Filippini E, Parrinello G, Nuzzo M, et al. Neuropsychological development of children born to patients with antiphospholipid syndrome. Arthritis Rheum. 2008;59(3):345–51. https://doi.org/10.1002/art.23311.

    Article  CAS  PubMed  Google Scholar 

  108. Brewster JA, Shaw NJ, Farquharson RG. Neonatal and pediatric outcome of infants born to mothers with antiphospholipid syndrome. J Perinat Med. 1999;27(3):183–7. https://doi.org/10.1515/JPM.1999.025.

    Article  CAS  PubMed  Google Scholar 

  109. Nalli C, Iodice A, Andreoli L, Galli J, Lojacono A, Motta M, et al. Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome. Lupus. 2017;26(5):552–8. https://doi.org/10.1177/0961203317694960.

    Article  CAS  PubMed  Google Scholar 

  110. Marder W, Romero VC, Ganser MA, Hyzy MA, Gordon C, McCune WJ, et al. Increased usage of special educational services by children born to mothers with systemic lupus erythematosus and antiphospholipid antibodies. Lupus Sci Med. 2014;1(1):e000034. https://doi.org/10.1136/lupus-2014-000034.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Berkun Y, Kenet G. Pediatric antiphospholipid syndrome. Isr Med Assoc J. 2008;10(1):45–7.

    PubMed  Google Scholar 

  112. Gordon O, Almagor Y, Fridler D, Mandel A, Qutteineh H, Yanir A, et al. De novo neonatal antiphospholipid syndrome: a case report and review of the literature. Semin Arthritis Rheum. 2014;44(2):241–5. https://doi.org/10.1016/j.semarthrit.2014.04.003.

    Article  PubMed  Google Scholar 

  113. Berkun Y, Simchen MJ, Strauss T, Menashcu S, Padeh S, Kenet G. Antiphospholipid antibodies in neonates with stroke--a unique entity or variant of antiphospholipid syndrome? Lupus. 2014;23(10):986–93. https://doi.org/10.1177/0961203314531842.

    Article  CAS  PubMed  Google Scholar 

  114. Paro-Panjan D, Kitanovski L, Avcin T. Neonatal antiphospholipid syndrome associated with heterozygous methylentetrahydrofolate reductase C677T and prothrombin G20210A gene mutations. Rheumatology. 2007;46(4):720–1. https://doi.org/10.1093/rheumatology/kem011.

    Article  CAS  PubMed  Google Scholar 

  115. Asherson RA, Piette JC. The catastrophic antiphospholipid syndrome 1996: acute multi-organ failure associated with antiphospholipid antibodies: a review of 31 patients. Lupus. 1996;5(5):414–7. https://doi.org/10.1177/096120339600500516.

    Article  CAS  PubMed  Google Scholar 

  116. Cabral M, Abadesso C, Conde M, Almeida H, Carreiro H. Catastrophic antiphospholipid syndrome: first signs in the neonatal period. Eur J Pediatr. 2011;170(12):1577–83. https://doi.org/10.1007/s00431-011-1548-9.

    Article  CAS  PubMed  Google Scholar 

  117. Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa MC, Piette JC, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003;12(7):530–4. https://doi.org/10.1191/0961203303lu394oa.

    Article  CAS  PubMed  Google Scholar 

  118. Cervera R, Font J, Gomez-Puerta JA, Espinosa G, Cucho M, Bucciarelli S, et al. Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome. Ann Rheum Dis. 2005;64(8):1205–9. https://doi.org/10.1136/ard.2004.025759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: updated diagnostic algorithms. Autoimmun Rev. 2010;10(2):74–9. https://doi.org/10.1016/j.autrev.2010.08.005.

    Article  PubMed  Google Scholar 

  120. Manco-Johnson MJ, Wang M, Goldenberg NA, Soep J, Gibson E, Knoll CM, et al. Treatment, survival, and thromboembolic outcomes of thrombotic storm in children. J Pediatr. 2012;161(4):682–8 e1. https://doi.org/10.1016/j.jpeds.2012.03.042.

    Article  PubMed  Google Scholar 

  121. Garcia-Carrasco M, Mendoza-Pinto C, Macias-Diaz S, Vazquez de Lara F, Etchegaray-Morales I, Galvez-Romero JL, et al. The role of infectious diseases in the catastrophic antiphospholipid syndrome. Autoimmun Rev. 2015;14(11):1066–71. https://doi.org/10.1016/j.autrev.2015.07.009.

    Article  CAS  PubMed  Google Scholar 

  122. Peddi VR, Kant KS. Catastrophic secondary antiphospholipid syndrome with concomitant antithrombin III deficiency. J Am Soc Nephrol. 1995;5(11):1882–7.

    CAS  PubMed  Google Scholar 

  123. Hudson N, Duffy CM, Rauch J, Paquin JD, Esdaile JM. Catastrophic haemorrhage in a case of paediatric primary antiphospholipid syndrome and factor II deficiency. Lupus. 1997;6(1):68–71. https://doi.org/10.1177/096120339700600110.

    Article  CAS  PubMed  Google Scholar 

  124. Asherson RA, Cervera R, Piette JC, Shoenfeld Y, Espinosa G, Petri MA, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine. 2001;80(6):355–77.

    Article  CAS  Google Scholar 

  125. Berman H, Rodriguez-Pinto I, Cervera R, Gregory S, de Meis E, Rodrigues CE, et al. Pediatric catastrophic antiphospholipid syndrome: descriptive analysis of 45 patients from the "CAPS Registry". Autoimmun Rev. 2014;13(2):157–62. https://doi.org/10.1016/j.autrev.2013.10.004A descriptive analysis of pediatric patients from the CAPS registry.

    Article  PubMed  Google Scholar 

  126. Arnaud L, Mathian A, Devilliers H, Ruffatti A, Tektonidou M, Forastiero R, et al. Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies. Autoimmun Rev. 2015;14(3):192–200. https://doi.org/10.1016/j.autrev.2014.10.019.

    Article  CAS  PubMed  Google Scholar 

  127. Arnaud L, Mathian A, Ruffatti A, Erkan D, Tektonidou M, Cervera R, et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis. Autoimmun Rev. 2014;13(3):281–91. https://doi.org/10.1016/j.autrev.2013.10.014.

    Article  CAS  Google Scholar 

  128. Jung H, Bobba R, Su J, Shariati-Sarabi Z, Gladman DD, Urowitz M, et al. The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum. 2010;62(3):863–8. https://doi.org/10.1002/art.27289.

    Article  CAS  PubMed  Google Scholar 

  129. Belizna C. Hydroxychloroquine as an anti-thrombotic in antiphospholipid syndrome. Autoimmun Rev. 2015;14(4):358–62. https://doi.org/10.1016/j.autrev.2014.12.006.

    Article  CAS  PubMed  Google Scholar 

  130. Bertolaccini ML, Contento G, Lennen R, Sanna G, Blower PJ, Ma MT, et al. Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome. J Autoimmun. 2016;75:30–8. https://doi.org/10.1016/j.jaut.2016.04.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Urbanski G, Caillon A, Poli C, Kauffenstein G, Begorre MA, Loufrani L, et al. Hydroxychloroquine partially prevents endothelial dysfunction induced by anti-beta-2-GPI antibodies in an in vivo mouse model of antiphospholipid syndrome. PLoS One. 2018;13(11):e0206814. https://doi.org/10.1371/journal.pone.0206814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Nuri E, Taraborelli M, Andreoli L, Tonello M, Gerosa M, Calligaro A, et al. Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome. Immunol Res. 2017;65(1):17–24. https://doi.org/10.1007/s12026-016-8812-z.

    Article  CAS  PubMed  Google Scholar 

  133. Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, Crowther M, Derksen R, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus. 2011;20(2):206–18. https://doi.org/10.1177/0961203310395803.

    Article  CAS  PubMed  Google Scholar 

  134. Jackson WG, Oromendia C, Unlu O, Erkan D, DeSancho MT, Antiphospholipid Syndrome Alliance for Clinical T, et al. Recurrent thrombosis in patients with antiphospholipid antibodies and arterial thrombosis on antithrombotic therapy. Blood Adv. 2017;1(25):2320–4. https://doi.org/10.1182/bloodadvances.2017008185.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Giron-Gonzalez JA, Garcia del Rio E, Rodriguez C, Rodriguez-Martorell J, Serrano A. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004;31(8):1560–7.

    PubMed  Google Scholar 

  136. Rodriguez-Pinto I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, Espinosa G, et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016;15(12):1120–4. https://doi.org/10.1016/j.autrev.2016.09.010A descriptive analysis of 500 patients enrolled in the International CAPS Registry.

    Article  Google Scholar 

  137. Iglesias-Jimenez E, Camacho-Lovillo M, Falcon-Neyra D, Lirola-Cruz J, Neth O. Infant with probable catastrophic antiphospholipid syndrome successfully managed with rituximab. Pediatrics. 2010;125(6):e1523–8. https://doi.org/10.1542/peds.2009-2939.

    Article  PubMed  Google Scholar 

  138. Nageswara Rao AA, Arteaga GM, Reed AM, Gloor JM, Rodriguez V. Rituximab for successful management of probable pediatric catastrophic antiphospholipid syndrome. Pediatr Blood Cancer. 2009;52(4):536–8. https://doi.org/10.1002/pbc.21878.

    Article  PubMed  Google Scholar 

  139. Berman H, Rodriguez-Pinto I, Cervera R, Morel N, Costedoat-Chalumeau N, Erkan D, et al. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmun Rev. 2013;12(11):1085–90. https://doi.org/10.1016/j.autrev.2013.05.004A descriptive analysis of the use of rituximab in pediatric CAPS.

    Article  CAS  PubMed  Google Scholar 

  140. Ruffatti A, Tarzia V, Fedrigo M, Calligaro A, Favaro M, Macor P, et al. Evidence of complement activation in the thrombotic small vessels of a patient with catastrophic antiphospholipid syndrome treated with eculizumab. Autoimmun Rev. 2019;18(5):561–3. https://doi.org/10.1016/j.autrev.2019.03.015.

    Article  PubMed  Google Scholar 

  141. Lonati PA, Scavone M, Gerosa M, Borghi MO, Pregnolato F, Curreli D, et al. Blood cell-bound C4d as a marker of complement activation in patients with the antiphospholipid syndrome. Front Immunol. 2019;10:773. https://doi.org/10.3389/fimmu.2019.00773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Chaturvedi S, Brodsky RA, McCrae KR. Complement in the pathophysiology of the antiphospholipid syndrome. Front Immunol. 2019;10:449. https://doi.org/10.3389/fimmu.2019.00449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Rovere-Querini P, Canti V, Erra R, Bianchi E, Slaviero G, D'Angelo A, et al. Eculizumab in a pregnant patient with laboratory onset of catastrophic antiphospholipid syndrome: a case report. Medicine. 2018;97(40):e12584. https://doi.org/10.1097/MD.0000000000012584.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Guillot M, Rafat C, Buob D, Coppo P, Jamme M, Rondeau E, et al. Eculizumab for catastrophic antiphospholipid syndrome-a case report and literature review. Rheumatology. 2018;57(11):2055–7. https://doi.org/10.1093/rheumatology/key228.

    Article  PubMed  Google Scholar 

  145. Zikos TA, Sokolove J, Ahuja N, Berube C. Eculizumab induces sustained remission in a patient with refractory primary catastrophic antiphospholipid syndrome. J Clin Rheumatol. 2015;21(6):311–3. https://doi.org/10.1097/RHU.0000000000000290.

    Article  PubMed  Google Scholar 

  146. Strakhan M, Hurtado-Sbordoni M, Galeas N, Bakirhan K, Alexis K, Elrafei T. 36-year-old female with catastrophic antiphospholipid syndrome treated with eculizumab: a case report and review of literature. Case Rep Hematol. 2014;2014:704371. https://doi.org/10.1155/2014/704371.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Shapira I, Andrade D, Allen SL, Salmon JE. Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis Rheum. 2012;64(8):2719–23. https://doi.org/10.1002/art.34440.

    Article  CAS  PubMed  Google Scholar 

  148. Tarr T, Lakos G, Bhattoa HP, Szegedi G, Shoenfeld Y, Kiss E. Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus. Lupus. 2007;16(5):324–8. https://doi.org/10.1177/0961203307077993.

    Article  CAS  PubMed  Google Scholar 

  149. Cervera R, Boffa MC, Khamashta MA, Hughes GR. The Euro-Phospholipid project: epidemiology of the antiphospholipid syndrome in Europe. Lupus. 2009;18(10):889–93. https://doi.org/10.1177/0961203309106832.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was partially supported by the Slovenian Research Agency grant L7-8274 and by the University Medical Center Ljubljana research grant 20180093.

Author information

Authors and Affiliations

  1. Pediatric Rheumatology, Children’s Hospital of University of Illinois, 840 S. Wood St, 1206 CSB, Chicago, 60612, USA

    Arzu Soybilgic

  2. Department of Allergology, Rheumatology and Clinical Immunology, Children’s Hospital, University Medical Center, Faculty of Medicine, University of Ljubljana, Bohoriceva 20, 1525, Ljubljana, Slovenia

    Tadej Avcin

Authors
  1. Arzu Soybilgic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tadej Avcin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arzu Soybilgic.

Ethics declarations

Conflict of Interest

Dr. Avcin reports grants from Slovenian Research Agency, during the conduct of the study; personal fees from AbbVie, personal fees from Octapharma, personal fees from Shire, outside the submitted work.

Dr. SOYBILGIC has nothing to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Antiphospholipid Syndrome

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soybilgic, A., Avcin, T. Pediatric APS: State of the Art. Curr Rheumatol Rep 22, 9 (2020). https://doi.org/10.1007/s11926-020-0887-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-020-0887-9

Keywords

Search

Navigation