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CD34+ Hematopoietic Stem Cell Count Is Predictive of Vascular Event Occurrence in Children with Sickle Cell Disease

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Abstract

Background/Objectives

Sickle cell disease (SCD) complications mostly result from vascular dysfunction, concerning systemic microvasculature and cerebral large vessels. The aim of this cohort study was to identify potential circulating biomarkers predictive for further vascular event occurrence in pediatric SCD.

Methods

We consecutively enrolled 108 children with SCD at steady state, aged 3–18 years old (median 9.8 years). Hematology, coagulation, hemolysis, endothelial, platelet and vascular activation parameters were recorded at inclusion. Neurovascular and systemic vascular events were prospectively recorded during a mean follow-up period of 27 months.

Results

Patients at steady state displayed significantly higher hemolysis and platelet activation markers, higher leukocyte, CD34+ hematopoietic stem cell and microvesicle counts, and a pro-coagulant profile compared to controls matched for age and ethnicity. Circulating endothelial cell or nucleosome level did not differ. During the follow-up period, 36 patients had at least one neurovascular (n = 12) or systemic vascular event (n = 25). In a multivariate model, high CD34+ cell count was the best predictor for the occurrence of a vascular event (OR 1.2 for 1000 cell/mL increase, 95% CI [1.049–1.4], p = 0.013, sensitivity 53%, specificity 84% for a threshold of 8675 cells/mL).

Conclusion

CD34+ cell count at steady state is a promising biomarker of further vascular event in children with SCD.

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Acknowledgements

The authors would like to thank Florence Desvard, Yann Brunel, Laurent Garcia, Aurélie Dumont, and Peggy Tournoux for their excellent technical assistance. The French Institute for Medical Research INSERM funded Dr. M. Kossorotoff for this study.

Author information

Authors and Affiliations

  1. Inserm UMR-S1140, Faculté de Pharmacie, Paris, France

    Manoelle Kossorotoff, Dominique Lasne, David M. Smadja & Pascale Gaussem

  2. AP-HP, Child Neurology, French center for pediatric stroke, Hôpital Universitaire Necker-Enfants malades, 149 rue de Sèvres, 75015, Paris, France

    Manoelle Kossorotoff & Isabelle Desguerre

  3. AP-HP, Pediatric Sickle Cell Clinic, Hôpital Universitaire Necker-Enfants malades and Laboratory of Excellence, GR-Ex, Paris, France

    Mariane De Montalembert & Valentine Brousse

  4. Sorbonne Paris Cité, Université Paris Descartes, Paris, France

    Mariane De Montalembert, Emmanuel Curis, David M. Smadja, Isabelle Desguerre, Damien Bonnet & Pascale Gaussem

  5. AP-HP, Laboratoire d’hématologie, Hôpital Universitaire Necker-Enfants malades, Paris, France

    Dominique Lasne

  6. Laboratoire de biomathématiques, plateau iB2, Faculté de Pharmacie, Paris, France

    Emmanuel Curis

  7. AP-HP, Service d’hématologie biologique, Hôpital Européen Georges Pompidou, Paris, France

    David M. Smadja, Sebastien Bertil & Pascale Gaussem

  8. Inserm UMR-S1076, UFR de Pharmacie, Aix Marseille Université, Marseille, France

    Romaric Lacroix & Elodie Masson

  9. AP-HP, M3C-Necker, Cardiologie Congénitale et Pédiatrique, Hôpital Universitaire Necker-Enfants malades, Paris, France

    Damien Bonnet

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  1. Manoelle Kossorotoff
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  2. Mariane De Montalembert
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  3. Valentine Brousse
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  4. Dominique Lasne
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  5. Emmanuel Curis
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  6. David M. Smadja
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Correspondence to Manoelle Kossorotoff.

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Kossorotoff, M., De Montalembert, M., Brousse, V. et al. CD34+ Hematopoietic Stem Cell Count Is Predictive of Vascular Event Occurrence in Children with Sickle Cell Disease. Stem Cell Rev and Rep 14, 694–701 (2018). https://doi.org/10.1007/s12015-018-9835-8

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