Manoelle Kossorotoff1,2, Mariane De Montalembert3,4, Valentine Brousse3, Dominique Lasne5,6, Emmanuel Curis4,7, David M Smadja5,4,8, Romaric Lacroix9, Sebastien Bertil8, Elodie Masson9, Isabelle Desguerre10,4, Damien Bonnet4,11, Pascale Gaussem5,4,8. 1. Inserm UMR-S1140, Faculté de Pharmacie, Paris, France. manoelle.kossorotoff@aphp.fr. 2. AP-HP, Child Neurology, French center for pediatric stroke, Hôpital Universitaire Necker-Enfants malades, 149 rue de Sèvres, 75015, Paris, France. manoelle.kossorotoff@aphp.fr. 3. AP-HP, Pediatric Sickle Cell Clinic, Hôpital Universitaire Necker-Enfants malades and Laboratory of Excellence, GR-Ex, Paris, France. 4. Sorbonne Paris Cité, Université Paris Descartes, Paris, France. 5. Inserm UMR-S1140, Faculté de Pharmacie, Paris, France. 6. AP-HP, Laboratoire d'hématologie, Hôpital Universitaire Necker-Enfants malades, Paris, France. 7. Laboratoire de biomathématiques, plateau iB2, Faculté de Pharmacie, Paris, France. 8. AP-HP, Service d'hématologie biologique, Hôpital Européen Georges Pompidou, Paris, France. 9. Inserm UMR-S1076, UFR de Pharmacie, Aix Marseille Université, Marseille, France. 10. AP-HP, Child Neurology, French center for pediatric stroke, Hôpital Universitaire Necker-Enfants malades, 149 rue de Sèvres, 75015, Paris, France. 11. AP-HP, M3C-Necker, Cardiologie Congénitale et Pédiatrique, Hôpital Universitaire Necker-Enfants malades, Paris, France.
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.
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.
Authors: S T Miller; L A Sleeper; C H Pegelow; L E Enos; W C Wang; S J Weiner; D L Wethers; J Smith; T R Kinney Journal: N Engl J Med Date: 2000-01-13 Impact factor: 91.245
Authors: Michael R DeBaun; Sharada A Sarnaik; Mark J Rodeghier; Caterina P Minniti; Thomas H Howard; Rathi V Iyer; Baba Inusa; Paul T Telfer; Melanie Kirby-Allen; Charles T Quinn; Françoise Bernaudin; Gladstone Airewele; Gerald M Woods; Julie Ann Panepinto; Beng Fuh; Janet K Kwiatkowski; Allison A King; Melissa M Rhodes; Alexis A Thompson; Mark E Heiny; Rupa C Redding-Lallinger; Fenella J Kirkham; Hernan Sabio; Corina E Gonzalez; Suzanne L Saccente; Karen A Kalinyak; John J Strouse; Jason M Fixler; Mae O Gordon; J Phillip Miller; Michael J Noetzel; Rebecca N Ichord; James F Casella Journal: Blood Date: 2011-11-17 Impact factor: 22.113
Authors: Ann T Farrell; Julie Panepinto; C Patrick Carroll; Deepika S Darbari; Ankit A Desai; Allison A King; Robert J Adams; Tabitha D Barber; Amanda M Brandow; Michael R DeBaun; Manus J Donahue; Kalpna Gupta; Jane S Hankins; Michelle Kameka; Fenella J Kirkham; Harvey Luksenburg; Shirley Miller; Patricia Ann Oneal; David C Rees; Rosanna Setse; Vivien A Sheehan; John Strouse; Cheryl L Stucky; Ellen M Werner; John C Wood; William T Zempsky Journal: Blood Adv Date: 2019-12-10