Study of Biological Markers in Children With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

Prospective Clinical Study on Early Inflammatory, Cell Adhesion and Hemostatic Plasmatic Markers of Endothelial Dysfunction in Children With Sickle Cell Disease (SCD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04839159
• Other study ID #: P2012/SCD1
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 10, 2012
• Est. completion date: June 30, 2021

Study information

• Verified date: April 2021
• Source: Queen Fabiola Children's University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sickle cell disease is associated with significant morbi-mortality hence the interest in an early and targeted care. At present, there is no plasmatic marker able to identify infants at higher risk of developping severe complications later in life. However, recent studies have demonstrated a correlation between certain complications of the disease and biomarkers of the endothelial dysfunction characterizing it.

Investigators prospectively followed a cohort of children diagnosed with SCD through the universal neonatal screening using inflammatory and haemostatic plasmatic markers to study their annual evolution. Investigators then will evaluate potential associations between these biological markers and the occurrence of SCD related complications. A secondary objective of this study is to evaluate the repercussions of therapeutic intervention on these markers.

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Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months and older

Eligibility

Inclusion Criteria:

• Patient aged less than 6 months

• Sickle cell syndrome SS, Sßthal or SC confirmed by hemoglobin electrophoresis

• Subjects legal representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to let participate their child in the study

Exclusion Criteria:

• Congenital abnormality other than sickle cell disease except for a glucose-6-phosphate-deshydrogenase

• Prematurity

• Initiation of the following therapies before enrollment: chronic transfusion regimen or bone marrow transplantation

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Other:
• Blood sampling
Blood sampling at the age of 6 and 12 months, 2-3-4 years
• Blood sampling
Blood sampling before any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres

Locations

Country	Name	City	State
Belgium	CHU Saint Pierre	Brussels
Belgium	HIS - Site Etterbeek-Ixelles	Brussels
Belgium	Hôpital Universitaire Des Enfants Reine Fabiola	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Queen Fabiola Children's University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (11)

Ballas SK, Lieff S, Benjamin LJ, Dampier CD, Heeney MM, Hoppe C, Johnson CS, Rogers ZR, Smith-Whitley K, Wang WC, Telen MJ; Investigators, Comprehensive Sickle Cell Centers. Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol. 2010 Jan;85(1):6-13. doi: 10.1002/ajh.21550. — View Citation

Charrin E, Ofori-Acquah SF, Nader E, Skinner S, Connes P, Pialoux V, Joly P, Martin C. Inflammatory and oxidative stress phenotypes in transgenic sickle cell mice. Blood Cells Mol Dis. 2016 Nov;62:13-21. doi: 10.1016/j.bcmd.2016.10.020. Epub 2016 Oct 28. — View Citation

Garrido VT, Proença-Ferreira R, Dominical VM, Traina F, Bezerra MA, de Mello MR, Colella MP, Araújo AS, Saad ST, Costa FF, Conran N. Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease. Br J Haematol. 2012 Sep;158(6):788-97. doi: 10.1111/j.1365-2141.2012.09218.x. Epub 2012 Jul 6. — View Citation

Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med. 2008 Nov 20;359(21):2254-65. doi: 10.1056/NEJMra0804411. Review. — View Citation

Gulbis B, Cotton F, Ferster A, Ketelslegers O, Dresse MF, Rongé-Collard E, Minon JM, Lé PQ, Vertongen F. Neonatal haemoglobinopathy screening in Belgium. J Clin Pathol. 2009 Jan;62(1):49-52. doi: 10.1136/jcp.2008.060517. — View Citation

Hoppe C, Klitz W, Noble J, Vigil L, Vichinsky E, Styles L. Distinct HLA associations by stroke subtype in children with sickle cell anemia. Blood. 2003 Apr 1;101(7):2865-9. Epub 2002 Nov 27. — View Citation

Horan J, Lerner N. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000 May 25;342(21):1612-3. — View Citation

Miller ST, Sleeper LA, Pegelow CH, Enos LE, Wang WC, Weiner SJ, Wethers DL, Smith J, Kinney TR. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000 Jan 13;342(2):83-9. — View Citation

Quinn CT, Lee NJ, Shull EP, Ahmad N, Rogers ZR, Buchanan GR. Prediction of adverse outcomes in children with sickle cell anemia: a study of the Dallas Newborn Cohort. Blood. 2008 Jan 15;111(2):544-8. Epub 2007 Oct 1. — View Citation

Sarray S, Saleh LR, Lisa Saldanha F, Al-Habboubi HH, Mahdi N, Almawi WY. Serum IL-6, IL-10, and TNFa levels in pediatric sickle cell disease patients during vasoocclusive crisis and steady state condition. Cytokine. 2015 Mar;72(1):43-7. doi: 10.1016/j.cyto.2014.11.030. Epub 2015 Jan 5. — View Citation

Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet. 2017 Jul 15;390(10091):311-323. doi: 10.1016/S0140-6736(17)30193-9. Epub 2017 Feb 1. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasmatic levels of IL-6 at 12 months of age	Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of IL-6 at 6 months of age	Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of IL-6 at 2 years of age	Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of IL-6 at 3 years of age	Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of IL-6 at 4 years of age	Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of IL-6 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of IL-1ß at 6 months of age	Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of IL-1ß at 12 months of age	Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of IL-1ß at 2 years of age	Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of IL-1ß at 3 years of age	Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of IL-1ß at 4 years of age	Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of IL-1ß before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of IL-8 at 6 months of age	Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of IL-8 at 12 months of age	Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of IL-8 at 2 years of age	Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of IL-8 at 3 years of age	Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of IL-8 at 4 years of age	Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of IL-8 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of IL-10 at 6 months of age	Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of IL-10 at 12 months of age	Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of IL-10 at 2 years of age	Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of IL-10 at 3 years of age	Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of IL-10 at 4 years of age	Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of IL-10 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of IL-12 at 6 months of age	Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of IL-12 at 12 months of age	Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of IL-12 at 2 years of age	Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of IL-12 at 3 years of age	Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of IL-12 at 4 years of age	Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of IL-12 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of TNF alpha at 6 months of age	Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of TNF alpha at 12 months of age	Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of TNF alpha at 2 years of age	Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of TNF alpha at 3 years of age	Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of TNF alpha at 4 years of age	Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of TNF alpha before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of ICAM-1 at 6 months of age	Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of ICAM-1 at 12 months of age	Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of ICAM-1 at 2 years of age	Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of ICAM-1 at 3 years of age	Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of ICAM-1 at 4 years of age	Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of ICAM-1 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of VCAM-1 at 6 months of age	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of VCAM-1 at 12 months of age	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of VCAM-1 at 2 years of age	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of VCAM-1 at 3 years of age	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of VCAM-1 at 4 years of age	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of VCAM-1 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic VCAM-1 levels after in vitro stimulation with LPS	Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay after in vitro stimulation with LPS	Plasmatic level of VCAM-1 after in vitro stimulation with LPS
Secondary	Plasmatic levels of E-selectine at 6 months of age	Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of E-selectine at 12 months of age	Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of E-selectine at 2 years of age	Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of E-selectine at 3 years of age	Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of E-selectine at 4 years of age	Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of E-selectine before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of P-selectine at 6 months of age	Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of P-selectine at 12 months of age	Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of P-selectine at 2 years of age	Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of P-selectine at 3 years of age	Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of P-selectine at 4 years of age	Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of P-selectine before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 6 months of age	Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 12 months of age	Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 2 years of age	Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 3 years of age	Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 4 years of age	Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of VEGF before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay	Before the introduction of any new sickle cell disease treatment
Secondary	Lag time parameter in thrombin generation assay at 6 months of age	Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	6 months of age
Secondary	Lag time parameter in thrombin generation assay at 12 months of age	Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	12 months of age
Secondary	Lag time parameter in thrombin generation assay at 2 years of age	Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	2 years of age
Secondary	Lag time parameter in thrombin generation assay at 3 years of age	Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	3 years of age
Secondary	Lag time parameter in thrombin generation assay at 4 years of age	Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	4 years of age
Secondary	Lag time parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	Before the introduction of any new sickle cell disease treatment
Secondary	Peak height parameter in thrombin generation assay at 6 months of age	Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	6 months of age
Secondary	Peak height parameter in thrombin generation assay at 12 months of age	Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	12 months of age
Secondary	Peak height parameter in thrombin generation assay at 2 years of age	Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	2 years of age
Secondary	Peak height parameter in thrombin generation assay at 3 years of age	Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	3 years of age
Secondary	Peak height parameter in thrombin generation assay at 4 years of age	Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	4 years of age
Secondary	Peak height parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	Before the introduction of any new sickle cell disease treatment
Secondary	Time to peak parameter in thrombin generation assay at 6 months of age	Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method	6 months of age
Secondary	Time to peak parameter in thrombin generation assay at 12 months of age	Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method	12 months of age
Secondary	Time to peak parameter in thrombin generation assay at 2 years of age	Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method	2 years of age
Secondary	Time to peak parameter in thrombin generation assay at 3 years of age	Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method	3 years of age
Secondary	Time to peak parameter in thrombin generation assay at 4 years of age	Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method	4 years of age
Secondary	Time to peak parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method	Before the introduction of any new sickle cell disease treatment
Secondary	Endogenous thrombin potential parameter in thrombin generation assay at 6 months of age	Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	6 months of age
Secondary	Endogenous thrombin potential parameter in thrombin generation assay at 12 months of age	Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	12 months of age
Secondary	Endogenous thrombin potential parameter in thrombin generation assay at 2 years of age	Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	2 years of age
Secondary	Endogenous thrombin potential parameter in thrombin generation assay at 3 years of age	Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	3 years of age
Secondary	Endogenous thrombin potential parameter in thrombin generation assay at 4 years of age	Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	4 years of age
Secondary	Endogenous thrombin potential parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method.	before the introduction of any new sickle cell disease treatment
Secondary	Plasmatic levels of Factor VIII at 6 months of age	Measurement of plasmatic levels of Factor VIII by flow cytometric assay	6 months of age
Secondary	Plasmatic levels of Factor VIII at 12 months of age	Measurement of plasmatic levels of Factor VIII by flow cytometric assay	12 months of age
Secondary	Plasmatic levels of Factor VIII at 2 years of age	Measurement of plasmatic levels of Factor VIII by flow cytometric assay	2 years of age
Secondary	Plasmatic levels of Factor VIII at 3 years of age	Measurement of plasmatic levels of Factor VIII by flow cytometric assay	3 years of age
Secondary	Plasmatic levels of Factor VIII at 4 years of age	Measurement of plasmatic levels of Factor VIII by flow cytometric assay	4 years of age
Secondary	Plasmatic levels of Factor VIII before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres	Measurement of plasmatic levels of Factor VIII by flow cytometric assay	Before the introduction of any new sickle cell disease treatment