Although Sickle Cell Anemia (SCA) has been characterized at the molecular level, the pathophysiology of its protein manifestation the vasocclusive crisis (VOC) still remains obscure. The exact events that lead to microcirculatory impairment and obstruction by sickled erythrocytes involve a complex and dynamic sequence of events that dependent presumably as much on microcirculatory tone, the activation state of the endothelium, white cells, platelets, and the fluid phases of coagulation as it does on the surface and internal characteristics of the red cell and its content of sickle and fetal hemoglobin. This Center grant will attempt to address the areas enumerated above in a unique and prospective fashion with focus on the crucial window of time during which a watershed change occurs in the erythrocyte's internal characteristics i.e.-its hemoglobin content of S and F. We will meticulously correlate how these physiologic changes in hemoglobin content during the first few years of life will affect the state of activation of the other cellular elements of blood, coagulation factors and endothelium, and how these changes effect the protein clinical manifestations of the disease-VOC and the occurrence of pain. The incidence and the attributes of sickle pain in these infants and young children will be assessed in a comprehensive and prospective longitudinal study. Additionally, our research program will explore at the cellular and molecular level the rationale for potential use of interventional strategies directed at one of the life threatening complications of Sickle Cell Disease, the acute chest syndrome, and also investigate a second and interventional program designed for our children in late childhood and early adolescence which will increase their resilience and perceived control over their lives and illness. Thus, this Center Grant seeks to address various aspect of basic and translational research besides providing the support our patients require to lead independent and productive lives. The research projects will be supported by the traditional aspects of a Comprehensive Sickle Cell Center including education and counseling services, a diagnostic and laboratory core, and appropriate statistical and administrative support.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Comprehensive Center (P60)
Project #
5P60HL062148-04
Application #
6390241
Study Section
Special Emphasis Panel (ZHL1-CSR-Q (S1))
Program Officer
Evans, Gregory
Project Start
1998-06-08
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
4
Fiscal Year
2001
Total Cost
$1,749,484
Indirect Cost
Name
Thomas Jefferson University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Dampier, Carlton; Ely, Beth; Brodecki, Darcy et al. (2014) Pain characteristics and age-related pain trajectories in infants and young children with sickle cell disease. Pediatr Blood Cancer 61:291-6
Setty, B N Yamaja; Key, Nigel S; Rao, A Koneti et al. (2012) Tissue factor-positive monocytes in children with sickle cell disease: correlation with biomarkers of haemolysis. Br J Haematol 157:370-80
Barakat, Lamia P; Patterson, Chavis A; Daniel, Lauren C et al. (2008) Quality of life among adolescents with sickle cell disease: mediation of pain by internalizing symptoms and parenting stress. Health Qual Life Outcomes 6:60
Barakat, Lamia P; Patterson, Chavis A; Weinberger, Beverley Slome et al. (2007) A prospective study of the role of coping and family functioning in health outcomes for adolescents with sickle cell disease. J Pediatr Hematol Oncol 29:752-60
Ely, Beth; Alexander, Leslie B; Reed, Monica (2005) The working alliance in pediatric chronic disease management: a pilot study of instrument reliability and feasibility. J Pediatr Nurs 20:190-200
Stuart, Marie J; Nagel, Ronald L (2004) Sickle-cell disease. Lancet 364:1343-60
Dampier, Carlton; Setty, B N Yamaja; Eggleston, Barry et al. (2004) Vaso-occlusion in children with sickle cell disease: clinical characteristics and biologic correlates. J Pediatr Hematol Oncol 26:785-90
Dampier, Carlton; Ely, Elizabeth; Eggleston, Barry et al. (2004) Physical and cognitive-behavioral activities used in the home management of sickle pain: a daily diary study in children and adolescents. Pediatr Blood Cancer 43:674-8
Sharan, K; Surrey, S; Ballas, S et al. (2004) Association of T-786C eNOS gene polymorphism with increased susceptibility to acute chest syndrome in females with sickle cell disease. Br J Haematol 124:240-3
Setty, B N Yamaja; Stuart, Marie J; Dampier, Carlton et al. (2003) Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology. Lancet 362:1450-5

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