Skip to main content
SpringerLink
Log in

Madrid Newborn Sickle Cell Disease Cohort: clinical outcomes, stroke prevention and survival

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

In May 2003, Madrid established the universal newborn screening (NBS) for sickle cell disease (SCD). However, there are no studies resembling the evolution of a SCD neonate cohort followed according to national guidelines in Spain. The aim of this study is to describe the morbimortality and the stroke prevention programme in patients diagnosed by SCD NBS in Madrid. This is a multicentre, observational, prospective cohort study between 2003 and 2018; 187 patients diagnosed with SCD were included (151 HbSS, 6 HbSβ0, 27 HbSC, 3 HbSβ +), and median follow-up was 5.2 years (0.03–14.9). There were 5 deaths: 2 related to SCD in patients with severe genotype (HbSS/HbSβ0). Overall survival reached 95% and SCD-related survival 96.8%. The most frequent events were fever without focus, vaso-occlusive crises and acute chest syndromes. Eight strokes occurred in 5 patients which led to a 90.7% stroke-free survival in severe genotype patients (first stroke rate, 0.54 per 100 patient-years). Transcranial Doppler (TCD) was performed in 95% of eligible patients; 75% of children with pathological TCD remained stroke-free. Regarding HbSS/HbSβ0 patients, 50.1% received hydroxyurea and 9.5% haematopoietic stem cell transplantation. This study reflects the evolution of Madrid SCD cohort and provides morbimortality data similar to other developed countries.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data used in this study are not available.

Abbreviations

ACS :

Acute chest syndrome

CSSCD :

The Cooperative Study of Sickle Cell Disease

VOC :

Vaso-occlusive crisis

EAF :

Erythrocytapheresis

GVHD :

Graft-versus-host disease

HGUGM :

Gregorio Marañón General University Hospital

HSCT :

Haematopoietic stem cell transplantation

HU :

Hydroxyurea

MO :

Bone marrow

MRA :

Magnetic resonance angiography

MRI :

Magnetic resonance imaging

NBS :

Newborn screening

OS :

Overall survival

SCD :

Sickle cell disease

TCD :

Transcranial Doppler ultrasound

References

  1. Quinn CT, Rogers ZR, Buchanan GR (2004) Survival of children with sickle cell disease. Blood 103(11):4023–4027

    Article  CAS  PubMed  Google Scholar 

  2. Quinn CT, Rogers ZR, Mccavit TL, Buchanan GR (2010) Improved survival of children and adolescents with sickle cell disease. Blood 115(17):3447–3452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Telfer P, Coen P, Chakravorty S, Wilkey O, Evans J, Newell H et al (2007) Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica 92(7):905–912

  4. Bernaudin F, Verlhac S, Arnaud C, Kamdem A, Chevret S, Hau I, Coïc L, Leveillé E, Lemarchand E, Lesprit E, Abadie I, Medejel N, Madhi F, Lemerle S, Biscardi S, Bardakdjian J, Galactéros F, Torres M, Kuentz M, Ferry C, Socié G, Reinert P, Delacourt C, Berna DC (2011) Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood. 117(4):1130–40

    Article  CAS  PubMed  Google Scholar 

  5. Chaturvedi S, Debaun MR (2016) Evolution of sickle cell disease from a life-threatening disease of children to a chronic disease of adults: the last 40 years. Am J Hematol 91(1):5–14

    Article  PubMed  Google Scholar 

  6. Vichinsky E, Hurst D, Earles A, Kleman K, Lubin B (1988) Newborn screening for sickle cell disease: effect on mortality. Pediatrics 81(6):749–55

  7. Lee A, Thomas P, Cupidore L, Serjeant B, Serjeant G (1995) Improved survival in homozygous sickle cell disease: lessons from a cohort study. BMJ 11(7020):1600–1602

  8. Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G et al (1986) Prophylaxis with oral penicillin in children with sickle cell anemia. N Engl J Med 314(25):1593–1599

  9. Adamkiewicz TV, Silk BJ, Howgate J, Baughman W, Strayhorn G et al (2008) Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life. Pediatrics 121(3):562–569

    Article  PubMed  Google Scholar 

  10. Halasa NB, Shankar SM, Talbot TR, Arbogast PG, Mitchel EF, Wang WC et al (2007) Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 44(11):1428–1433

    Article  CAS  PubMed  Google Scholar 

  11. de Castro Lopes, Lobo C, Pinto JFC, Nascimento EM, Moura PG, Cardoso GP, Hankins JS (2013) The effect of hydroxycarbamide therapy on survival of children with sickle cell disease. Br J Haematol. 161(6):852–60

    Article  Google Scholar 

  12. Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP et al (2011) Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet 377(9778):1663–1672. https://doi.org/10.1016/S0140-6736(11)60355-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C et al (1998) Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 339(1):5–11

  14. Rogers DW, Clarke JM, Cupidore L, Ramlal AM, Sparke BR, Serjeant GR (1978) Early deaths in Jamaican children with sickle cell disease. Br Med J 1(6126):1515–1516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gill FM, Sleeper L a, Weiner SJ, Brown AK, Bellevue R, Grover R, et al. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. Blood. 1995;86(2):776–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7606007

  16. García-Morín M, Bardón-Cancho EJ, Beléndez C, Zamarro R, Béliz-Mendiola C, González-Rivera M, Vecilla C, Llorente-Otones L, Pérez-Alonso V, Román SS, Sebastián E, Dulín E, Cela E (2020) Fifteen years of newborn sickle cell disease screening in Madrid, Spain: an emerging disease in a European country. Ann Hematol 99(7):1465–1474. https://doi.org/10.1007/s00277-020-04044-z

    Article  PubMed  Google Scholar 

  17. Bardón Cancho EJ, García-Morín M, Beléndez C, Velasco P, Benéitez D, Ruiz-Llobet A et al (2020) Update of the Spanish registry of haemoglobinopathies in children and adults. Med Clin (Barc) 155(3):95–103

    Article  PubMed  Google Scholar 

  18. Ministerio de Sanidad SS e I. Centros, Servicios y Unidades de Referencia del Sistema Nacional de Salud [Internet]. 2020. Available from: https://www.mscbs.gob.es/profesionales/CentrosDeReferencia/CentrosCSUR.htm. Accessed 12 Nov 2023

  19. Sociedad Española De Hematología Pediátrica (SEHP). Protocolo de Anemia de Células Falciformes o Drepanocitosis DREP-2002-SEHP. 2002. Available from: https://www.comunidad.madrid/hospital/gregoriomaranon/file/3425/download?token=fPtjNdS1. Accessed 12 Nov 2023

  20. SEHOP. Guía de práctica clínica de enfermedad de células falciformes. Sociedad Española de Hematología y Oncología Pediátricas SEHOP-2010. Available from: http://www.sehop.org/wp-content/uploads/2013/05/GU%C3%8DA-FALCIFORME-SEHOP-2010.pdf. Accessed 12 Nov 2023

  21. SEHOP. Enfermedad de células falciformes. Guía de práctica clínica Sociedad Española de Hematología y Oncología Pediátricas SEHOP-2019. ISBN: 978–84–944935–5–3. Available from: http://www.sehop.org/wp-content/uploads/2019/03/Guía-SEHOP-Falciforme-2019.pdf. Accessed 12 Nov 2023

  22. Brousse V, Kossorotoff M, de Montalembert M (2015) How I manage cerebral vasculopathy in children with sickle cell disease. Br J Haematol 170(5):615–625

    Article  PubMed  Google Scholar 

  23. Yazer MH, Lozano M, Crighton G, Greenway A, Comande M, Savoia H et al (2016) Transfusion service management of sickle-cell disease patients. Vox Sang 110(3):288–294

    Article  CAS  PubMed  Google Scholar 

  24. Regalado-Artamendi I, Pérez-Corral AM, García-Morín M, Cela E, Beléndez C, Bardón-Cancho EJ et al (2021) Complete RH and Kell matching related to low alloimmunisation risk in sickle cell disease: prevalence and risk factors of alloimmunisation in a Spanish Tertiary Care National Reference Centre. Blood Transfus 19(4):292–299

    PubMed  PubMed Central  Google Scholar 

  25. Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K, Krishnamurti L, Smith WR, Panepinto JA, Weatherall DJ, Costa FF, Vichinsky EP (2018) Sickle cell disease. Nat Rev Dis Primers 4:18010. https://doi.org/10.1038/nrdp.2018.10

    Article  PubMed  Google Scholar 

  26. Instituto de Estadística de la Comunidad de Madrid. Informe de población extranjera empadronada en la Comunidad de Madrid, enero 2018. 2018; Available from: https://www.comunidad.madrid/sites/default/files/informe_de_poblacion_enero_2018_definitivo.pdf

  27. Oligbu G, Fallaha M, Pay L, Ladhani S (2019) Risk of invasive pneumococcal disease in children with sickle cell disease in the era of conjugate vaccines: a systematic review of the literature. Br J Haematol 185(4):743–751

    Article  PubMed  Google Scholar 

  28. Scothorn DJ, Price C, Schwartz D, Terrill C, Buchanan GR, Shurney W et al (2002) Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke. J Pediatr 140(3):348–354

    Article  PubMed  Google Scholar 

  29. Dobson SR, Holden KR, Nietert PJ, Cure JK, Laver JH, Disco D et al (2002) Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events. Blood 99(9):3144–3150

    Article  CAS  PubMed  Google Scholar 

  30. Moser FG, Miller ST, Bello JA, Pegelow CH, Zimmerman RA, Wang WC et al (1996) The spectrum of brain MR abnormalities in sickle-cell disease: a report from the cooperative study of sickle cell disease. Am J Neuroradiol 17(5):965–972

    CAS  PubMed  PubMed Central  Google Scholar 

  31. DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA et al (2014) Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med 371(8):699–710

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gluckman E, Cappelli B, Bernaudin F, Labopin M, Volt F, Carreras J et al (2017) Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood 129(11):1548–1556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Qureshi A, Kaya B, Pancham S, Keenan R, Anderson J, Akanni M et al (2018) Guidelines for the use of hydroxycarbamide in children and adults with sickle cell disease: a British Society for Haematology Guideline. Br J Haematol 181(4):460–475

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank patients, their families, neonatal screening laboratory and also doctors and nursing staff at participating hospitals for their important work.

Funding

This study has not received any type of funding.

Author information

Authors and Affiliations

  1. Pediatric Oncology/Hematology/BMT Unit, Pediatric Department, Facultad de Medicina, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, C/ Maiquez, 9, 28007, Madrid, Spain

    Marina García-Morin, Eduardo J. Bardón-Cancho, Cristina Beléndez & Elena Cela

  2. Instituto Investigación Sanitaria Gregorio Marañón, Madrid, Spain

    Marina García-Morin, Eduardo J. Bardón-Cancho, Cristina Beléndez, José M. Bellón & Elena Cela

  3. Instituto Nacional de Investigación Biomédica en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain

    Cristina Beléndez & Elena Cela

  4. Newborn Screening Laboratory, Hospital General Universitario Gregorio Marañón, C/Maiquez, 9, 28007, Madrid, Spain

    Elena Dulín, Paula Blanco-Soto & Carolina Puertas-López

  5. Nursery, Sickle Cell Disease Newborn Screening, Pediatric Department, Pediatric Oncology/Hematology/BMT Unit, Madrid, Spain

    Mar Prieto-Medina

  6. Hematology Unit, Pediatric Department, Hospital Universitario de Móstoles, Móstoles, Madrid, Spain

    Áurea Cervera-Bravo

  7. Hematology Unit, Pediatric Department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain

    Lucía Llorente-Otones

  8. Pediatric Oncology and Hematology Unit, Pediatric Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Vanesa Pérez-Alonso

  9. Pediatric Oncology and Hematology Department, Hospital Universitario La Paz, Madrid, Spain

    Sonsoles San-Román

  10. Hematology Unit, Pediatric Department, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain

    Cruz Vecilla-Rivelles

  11. Hematology Department, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain

    Montserrat López-Rubio

  12. Pediatric Oncology and Hematology Department, Hospital Infantil Niño Jesús, Madrid, Spain

    Elena Sebastián

Authors
  1. Marina García-Morin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduardo J. Bardón-Cancho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Beléndez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Dulín
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paula Blanco-Soto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carolina Puertas-López
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mar Prieto-Medina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Áurea Cervera-Bravo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lucía Llorente-Otones
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vanesa Pérez-Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sonsoles San-Román
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Cruz Vecilla-Rivelles
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Montserrat López-Rubio
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Elena Sebastián
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. José M. Bellón
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Elena Cela
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MGM and EC designed and directed the project; MGM has mainly performed the data collection, but with the participation of EJBC, ACB, LLO, VPA, SSR, ES, CVR and MLR. MGM has performed the data analysis with the help of the biostatistician JMB. MGM has written the article with the collaboration and revision of EC, CB and ACB.

Corresponding author

Correspondence to Eduardo J. Bardón-Cancho.

Ethics declarations

Ethics approval and consent to participate

This is a human study that has been approved by the ethics committee “COMITÉ de ÉTICA HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN” and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study has also been approved by the Spanish Data Protection Agency.

Consent for publication

All authors declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere.

We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfy the criteria for authorship not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.

Conflicts of interest

The authors declare that they have no conflict of interest. The authors have non-financial interests to disclose. The authors have no competing interests to declare that are relevant to the content of this article. The authors have no financial or proprietary interests in any material discussed in this article.

Informed consent

Informed consent was obtained from all parents for being included in the study.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

García-Morin, M., Bardón-Cancho, E.J., Beléndez, C. et al. Madrid Newborn Sickle Cell Disease Cohort: clinical outcomes, stroke prevention and survival. Ann Hematol 103, 373–383 (2024). https://doi.org/10.1007/s00277-023-05539-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05539-1

Keywords

Search

Navigation