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Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study

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Valentine Brousse, Sara El Hoss, Naïm Bouazza, Cécile Arnaud, Francoise Bernaudin, Béatrice Pellegrino, Corinne Guitton, Marie Hélène Odièvre-Montanié, David Mames, Chantal Brouzes, Véronique Picard, Thao Nguyen-Khoa, Catia Pereira, Claudine Lapouméroulie, Serge Pissard, Kate Gardner, Stephan Menzel, Caroline Le Van Kim, Yves Colin-Aronovicz, Pierre Buffet & 5 more Narla Mohandas, Caroline Elie, Micheline Maier-Redelsperger, Wassim El Nemer, Mariane de Montalembert

Original languageEnglish
Pages (from-to)1411-1419
Number of pages9
JournalAmerican Journal of Hematology
Issue number11
Published1 Nov 2018

King's Authors


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 ( 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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