Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study
Open accessAbstract
In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi‐center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event—acute splenic sequestration (ASS), vaso‐occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death—was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow‐up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ‐globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11‐0.73) and 0.16 (0.06‐0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.
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In 57 infants studied at 4.4±1 months of age and followed for approximately 19 months, HbF fell from 42% to 21% and was the strongest prognostic factor for disease complications.
“To identify prognostic factors for clinical complications, 57 infants were studied at 4.4 6 1 months of age and followed for ;19 months.HbF, which fell from 42% to 21% during the observation period, was the strongest prognostic factor for disease complications.64”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [64]
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Cites
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320 · see citing works
Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members
Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H., Jordan, L., Lanzkron, S. M., Lottenberg, R., Savage, W. J., et al. (2014) · JAMA · doi:10.1001/jama.2014.10517 · Cited by 1,599 · see citing works
Ware, R. E., de Montalembert, M., Tshilolo, L. M., & Abboud, M. R. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30193-9 · Cited by 1,004 · see citing works
Wang, W. C., Ware, R. E., Miller, S. T., Iyer, R. V., Casella, J. F., Minniti, C. P., Rana, S., Thornburg, C. D., Rogers, Z. R., Kalpatthi, R. V., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60355-3 · Cited by 803 · see citing works
Acute Chest Syndrome in Sickle Cell Disease: Clinical Presentation and Course
Vichinsky, E. P., Styles, L. A., Colangelo, L. H., Wright, E. C., Castro, O., Nickerson, B., & Disease, T. C. S. O. S. C. (1997) · Blood · doi:10.1182/blood.v89.5.1787 · Cited by 573 · see citing works
Prediction of Adverse Outcomes in Children with Sickle Cell Disease
Miller, S. T., Sleeper, L. A., Pegelow, C. H., Enos, L. E., Wang, W. C., Weiner, S. J., Wethers, D. L., Smith, J., & Kinney, T. R. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001133420203 · Cited by 508 · see citing works
Clark, M., Mohandas, N., & Shohet, S. B. (1983) · Blood · doi:10.1182/blood.v61.5.899.899 · Cited by 385 · see citing works
Self-citationTelfer, P. T., Coen, P. G., Chakravorty, S., Wilkey, O., Evans, J. P. M., Newell, H., Smalling, B., Amos, R. I. J., Stephens, A. D., Rogers, D., et al. (2007) · Haematologica · doi:10.3324/haematol.10937 · Cited by 356 · see citing works
The spleen and sickle cell disease: the sick(led) spleen
Brousse, V. A. M., Buffet, P. A., & Rees, D. C. (2014) · British Journal of Haematology · doi:10.1111/bjh.12950 · Cited by 291 · see citing works
Self-citationImpact of hydroxyurea on clinical events in the BABY HUG trial
Thornburg, C. D., Files, B. A., Luo, Z., Miller, S. T., Kalpatthi, R. V., Iyer, R. V., Seaman, P., Lebensburger, J. D., Alvarez, O. A., Thompson, B., et al. (2012) · Blood · doi:10.1182/blood-2012-03-419879 · Cited by 256 · see citing works
Adams, R. J. (2004) · Blood · doi:10.1182/blood-2003-08-2733 · Cited by 186 · see citing works
Biomarkers in sickle cell disease
Rees, D. C., & Gibson, J. S. (2011) · British Journal of Haematology · doi:10.1111/j.1365-2141.2011.08961.x · Cited by 153 · see citing works
Dodé, C., Krishnamoorthy, R., Lamb, J., & Rochette, J. (1993) · British Journal of Haematology · doi:10.1111/j.1365-2141.1993.tb04639.x · Cited by 147 · see citing works
Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer
Costa, L. M. D., Suner, L., Galimand, J., Bonnel, A., Pascreau, T., Couque, N., Fenneteau, O., & Mohandas, N. (2015) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2015.09.001 · Cited by 143 · see citing works
Self-citationReference Values and Hematologic Changes From Birth to 5 Years in Patients With Sickle Cell Disease
Brown, A. K. (1994) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1994.02170080026005 · Cited by 108 · see citing works
Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia
Makani, J., Menzel, S., Nkya, S. W., Cox, S. E., Drašar, E., Soka, D., Komba, A., Mgaya, J., Rooks, H., Vasavda, N., et al. (2010) · Blood · doi:10.1182/blood-2010-08-302703 · Cited by 101 · see citing works
Self-citationQuinn, C. T., Lee, N. J., Shull, E. P., Ahmad, N., Rogers, Z. R., & Buchanan, G. R. (2007) · Blood · doi:10.1182/blood-2007-07-100719 · Cited by 90 · see citing works
Sheehan, V., Luo, Z., Flanagan, J. M., Howard, T. A., Thompson, B. W., Wang, W. C., Kutlar, A., Ware, R. E., & BABY HUG Investigators (2013) · American Journal of Hematology · doi:10.1002/ajh.23457 · Cited by 89 · see citing works
Genetic association studies in β-hemoglobinopathies
Thein, S. L. (2013) · Hematology · doi:10.1182/asheducation-2013.1.354 · Cited by 78 · see citing works
Couque, N., Girard, D., Ducrocq, R., Boizeau, P., Haouari, Z., Missud, F., Holvoet, L., Ithier, G., Belloy, M., Odièvre, M., et al. (2016) · British Journal of Haematology · doi:10.1111/bjh.14015 · Cited by 76 · see citing works
Self-citationA potential regulatory region for the expression of fetal hemoglobin in sickle cell disease
Pissard, S., & Beuzard, Y. (1994) · Blood · doi:10.1182/blood.v84.1.331.331 · Cited by 61 · see citing works
Self-citationg(HbF): a genetic model of fetal hemoglobin in sickle cell disease
Gardner, K., Fulford, T., Silver, N., Rooks, H., Angelis, N., Allman, M., Nkya, S., Makani, J., Howard, J., Kesse-Adu, R., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2017009811 · Cited by 43 · see citing works
Self-citationErythroid Adhesion Molecules in Sickle Cell Anaemia Infants: Insights Into Early Pathophysiology
Brousse, V. A. M., Colin, Y., Pereira, C., Arnaud, C., Odièvre, M. H., Boutemy, A., Guitton, C., de Montalembert, M., Lapouméroulie, C., Picot, J., et al. (2014) · EBioMedicine · doi:10.1016/j.ebiom.2014.12.006 · Cited by 38 · see citing works
Self-citationA systematic review of the literature for severity predictors in children with sickle cell anemia
Meier, E. R., Fasano, R. M., & Levett, P. (2017) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2017.01.014 · Cited by 33 · see citing works
Crizanlizumab in Sickle Cell Disease
Yu, Z., Blankenship, L., & Jaiyesimi, I. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1703162 · Cited by 27 · see citing works
Meier, E. R., Byrnes, C., Lee, Y. T., Wright, E. C., Schechter, A. N., Luban, N. L. C., & Miller, J. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070794 · Cited by 25 · see citing works
Meier, E. R., Fasano, R. M., Estrada, M., He, J., Luban, N. L. C., & McCarter, R. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.10.031 · Cited by 22 · see citing works
Costa, C., Pissard, S., Girodon, E., et al. (2003) · Molecular Diagnosis · doi:10.1007/bf03260020 · Cited by 12 · see citing works
Self-citationAutomated analysis of mature red blood cells and reticulocytes in SS and SC disease
Maïer-Redelsperger, M., Flahault, A., Neonato, M. G., Girot, R., & Labie, D. (2004) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2004.03.005 · Cited by 9 · see citing works
Are the risks of treatment to cure a child with severe sickle cell disease too high?
de Montalembert, M., Brousse, V. A. M., Chakravorty, S., Pagliuca, A., Porter, J. B., Telfer, P. T., Vora, A. J., & Rees, D. C. (2017) · BMJ · doi:10.1136/bmj.j5250 · Cited by 8 · see citing works
Self-citationPicot, J., Goudot, C., Berkenou, J., et al. (2013) · American Journal of Hematology · doi:10.1002/ajh.23597 · Cited by 7 · see citing works
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Research works printed but not linked: 1
- [2]2. Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell dis- ease. Lancet. 2017;390:311-323.
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Fetal hemoglobin in sickle cell anemia
Steinberg, M. H. (2020) · Blood · doi:10.1182/blood.2020007645 · Cited by 136 · see citing works
- Authors
- Brousse, V., El Hoss, S., Bouazza, N., Arnaud, C., Bernaudin, F., Pellegrino, B., Guitton, C., Odièvre‐Montanié, M., Mames, D., Brouzes, C., Picard, V., Nguyen‐Khoa, T., Pereira, C., Lapouméroulie, C., Pissard, S., Gardner, K., Menzel, S., Le Van Kim, C., Colin‐Aronovicz, Y., Buffet, P., Mohandas, N., Elie, C., Maier‐Redelsperger, M., El Nemer, W., & de Montalembert, M.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- UMR_S 1134 Biologie Intégrée du Globule Rouge Université Sorbonne Paris Cité/Université Paris Diderot/INSERM/INTS/Laboratoire d'Excellence GR‐Ex Paris France
- Sorbonne Paris Cité (FR)
- Hôpital Intercommunal de Créteil (FR)
- Service de Pédiatrie Centre Hospitalier Intercommunal de Créteil Créteil France
- Centre Hospitalier Intercommunal de Poissy (FR)
- Bicêtre Hospital (FR)
- Service de Pédiatrie, Hôpital Universitaire Armand Trousseau Paris France
- Hôpital Tenon (FR)
- Inserm (FR)
- Centre Hospitalier Universitaire Henri-Mondor (FR)
- King's College London (GB)
- New York Blood Center (US)
- Hôpital Cochin (FR)
- Laboratoire d'Hématologie Hôpital Universitaire Tenon Paris France
- Service de Pédiatrie et Maladies Infectieuses Hôpital Universitaire Necker‐Enfants Malades Paris France
- Corresponding author
- Brousse, Valentine
- ORCID
- Venue
- American Journal of Hematology
- Publisher
- Wiley
- Published
- 2018-09-21
- Volume
- 93
- Issue
- 11
- Pages
- 1411-1419
- ISSN
- 0361-8609 (ISSN-L)
- 1096-8652
- OpenAlex
- W2888059503
- Cited by
- 25
- References
- 31
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- “Investissements d'avenir” of the French National Research Agency (ANR-11-IDEX-0005-02)
- Laboratory of Excellence GR-Ex (ANR-11-LABX-0051)
- Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris
- French Ministry of Health (P071228)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Keywords
- sickle cell disease, infants, prognostic factors, fetal hemoglobin, hemoglobin levels, acute splenic sequestration, vaso-occlusive crisis, transfusion requirements, cerebral blood flow velocity, hemoglobin S-beta thalassemia, disease severity, early biomarkers
- MeSH terms
- Anemia, Sickle Cell, Blood Transfusion, Female, Fetal Hemoglobin, Hemoglobins, Hospitalization, Humans, Infant, Longitudinal Studies, Male, Prognosis, Severity of Illness Index, Cohort Studies, Biomarkers
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