GENOTYPE IN CHILDREN AND ADOLESCENTS WITH SICKLE CELL DISEASE: RELATION TO VASCULAR COMPLICATIONS AND SUBCLINICAL ATHEROSCLEROSIS
(Abstract release date: 05/19/16)
EHA Library. ABDELGAWAD TANTAWY ZAGHLOUL A. 06/09/16; 135039; PB2139
Prof. AZZA ABDELGAWAD TANTAWY ZAGHLOUL
Contributions
Contributions
Abstract
Abstract: PB2139
Type: Publication Only
Background
Sickle cell disease (SCD) has a wide spectrum of complications. Many factors contribute to the variability in SCD including genetic determinants.
Aims
To assess the relation between different genotypes among 38 children and adolescents with SCD and vascular markers, iron overload as well as vascular complications and subclinical atherosclerosis.
Methods
SCD patients (21 males and 17 females), in steady state were studied. All patients were subjected to full history and thorough clinical examination with special emphasis on history of sickling crisis, cardiopulmonary disease, acute chest syndrome, stroke, bone manifestations, nephropathy, spleen status, transfusion history and hydroxyurea/chelation therapy. Laboratory investigations included hematological profile, liver and kidney functions, markers of hemolysis (lactate dehydrogenase [LDH] and indirect bilirubin) and serum ferritin. Soluble CD163 (sCD163) was measured by enzyme linked immunosorbent assay while analysis of platelet microparticles (PMPs) was done by flow cytometry. Pediatric SCD severity index was assessed based on both clinical and laboratory variables. DNA genotyping was identified using on polymerase chain reaction and reverse hybridization. Echocardiography and assessment of carotid intima media thickness were performed.
Results
Based upon DNA genotyping, patients were categorized as either homozygous sickle cell disease (HbSS) or heterozygous sickle cell disease (Hb S/β); 24 (63.2%) patients had sickle cell anemia (SCA), 10 (26.3%) patients had sickle βº thalassemia and 4 (10.5%) patients had sickle β+ thalassemia. Comparison between patients with SCA (n=24) and those with sickle β-thalassemia (n=14) revealed no significant difference as regards age, sex, anthropometric measures, Tanner stage, family history or residency (p>0.05). A trend towards higher incidence of consanguineous marriage among families of patients with sickle β-thalassemia was found (p=0.082). Patients with SCA had significantly higher incidence of pulmonary hypertension, acute chest syndrome, frequent sickling crisis, avascular bone necrosis and nehropathy while those with sickle β-thalassemia had higher incidence of splenectomy, viral hepatitits and heart disease (p<0.05). The degree of hemolysis and iron overload was increased in sickle β-thalassemia patients compared with SCA group as shown by elevated transfusion index, LDH and serum ferritin (p<0.05). Patients with SCA displayed an evident state of inflammation, vascular injury and subclinical atherosclerosis reflected by high white blood cells (p=0.018), monocyte count (p=0.017), HbS, sCD163 levels (p<0.001), PMPs (p<0.001) and CIMT (p=0.029). Upon comparing genotypes among patients with mild/moderate versus severe disease, SCA genotype represented the higher incidence in severity (80.8%) followed by sickle βº thalassemia (19.2%) while all patients with sickle β+ thalassemia (n=4) were in the mild/moderate group. Genotype, in addition to HbS and parameters of vascular dysfunction (sCD163, PMPs and CIMT) were independently related to disease severity in logistic regression analysis. The cutoff values the studied vascular markers in relation to disease severity were determined.
Conclusion
Our findings could be of pathophysiological importance, because they provide evidence that genotyping may not only have a role in predicting disease severity in young SCD patients but it is potentially involved in determining the type of vasculopathy developed in those patients, allowing better individualized treatment.
Session topic: E-poster
Keyword(s): Genotype, Pulmonary hypertension, Sickle cell disease, Vasoocclusive crisis
Type: Publication Only
Background
Sickle cell disease (SCD) has a wide spectrum of complications. Many factors contribute to the variability in SCD including genetic determinants.
Aims
To assess the relation between different genotypes among 38 children and adolescents with SCD and vascular markers, iron overload as well as vascular complications and subclinical atherosclerosis.
Methods
SCD patients (21 males and 17 females), in steady state were studied. All patients were subjected to full history and thorough clinical examination with special emphasis on history of sickling crisis, cardiopulmonary disease, acute chest syndrome, stroke, bone manifestations, nephropathy, spleen status, transfusion history and hydroxyurea/chelation therapy. Laboratory investigations included hematological profile, liver and kidney functions, markers of hemolysis (lactate dehydrogenase [LDH] and indirect bilirubin) and serum ferritin. Soluble CD163 (sCD163) was measured by enzyme linked immunosorbent assay while analysis of platelet microparticles (PMPs) was done by flow cytometry. Pediatric SCD severity index was assessed based on both clinical and laboratory variables. DNA genotyping was identified using on polymerase chain reaction and reverse hybridization. Echocardiography and assessment of carotid intima media thickness were performed.
Results
Based upon DNA genotyping, patients were categorized as either homozygous sickle cell disease (HbSS) or heterozygous sickle cell disease (Hb S/β); 24 (63.2%) patients had sickle cell anemia (SCA), 10 (26.3%) patients had sickle βº thalassemia and 4 (10.5%) patients had sickle β+ thalassemia. Comparison between patients with SCA (n=24) and those with sickle β-thalassemia (n=14) revealed no significant difference as regards age, sex, anthropometric measures, Tanner stage, family history or residency (p>0.05). A trend towards higher incidence of consanguineous marriage among families of patients with sickle β-thalassemia was found (p=0.082). Patients with SCA had significantly higher incidence of pulmonary hypertension, acute chest syndrome, frequent sickling crisis, avascular bone necrosis and nehropathy while those with sickle β-thalassemia had higher incidence of splenectomy, viral hepatitits and heart disease (p<0.05). The degree of hemolysis and iron overload was increased in sickle β-thalassemia patients compared with SCA group as shown by elevated transfusion index, LDH and serum ferritin (p<0.05). Patients with SCA displayed an evident state of inflammation, vascular injury and subclinical atherosclerosis reflected by high white blood cells (p=0.018), monocyte count (p=0.017), HbS, sCD163 levels (p<0.001), PMPs (p<0.001) and CIMT (p=0.029). Upon comparing genotypes among patients with mild/moderate versus severe disease, SCA genotype represented the higher incidence in severity (80.8%) followed by sickle βº thalassemia (19.2%) while all patients with sickle β+ thalassemia (n=4) were in the mild/moderate group. Genotype, in addition to HbS and parameters of vascular dysfunction (sCD163, PMPs and CIMT) were independently related to disease severity in logistic regression analysis. The cutoff values the studied vascular markers in relation to disease severity were determined.
Conclusion
Our findings could be of pathophysiological importance, because they provide evidence that genotyping may not only have a role in predicting disease severity in young SCD patients but it is potentially involved in determining the type of vasculopathy developed in those patients, allowing better individualized treatment.
Session topic: E-poster
Keyword(s): Genotype, Pulmonary hypertension, Sickle cell disease, Vasoocclusive crisis
Abstract: PB2139
Type: Publication Only
Background
Sickle cell disease (SCD) has a wide spectrum of complications. Many factors contribute to the variability in SCD including genetic determinants.
Aims
To assess the relation between different genotypes among 38 children and adolescents with SCD and vascular markers, iron overload as well as vascular complications and subclinical atherosclerosis.
Methods
SCD patients (21 males and 17 females), in steady state were studied. All patients were subjected to full history and thorough clinical examination with special emphasis on history of sickling crisis, cardiopulmonary disease, acute chest syndrome, stroke, bone manifestations, nephropathy, spleen status, transfusion history and hydroxyurea/chelation therapy. Laboratory investigations included hematological profile, liver and kidney functions, markers of hemolysis (lactate dehydrogenase [LDH] and indirect bilirubin) and serum ferritin. Soluble CD163 (sCD163) was measured by enzyme linked immunosorbent assay while analysis of platelet microparticles (PMPs) was done by flow cytometry. Pediatric SCD severity index was assessed based on both clinical and laboratory variables. DNA genotyping was identified using on polymerase chain reaction and reverse hybridization. Echocardiography and assessment of carotid intima media thickness were performed.
Results
Based upon DNA genotyping, patients were categorized as either homozygous sickle cell disease (HbSS) or heterozygous sickle cell disease (Hb S/β); 24 (63.2%) patients had sickle cell anemia (SCA), 10 (26.3%) patients had sickle βº thalassemia and 4 (10.5%) patients had sickle β+ thalassemia. Comparison between patients with SCA (n=24) and those with sickle β-thalassemia (n=14) revealed no significant difference as regards age, sex, anthropometric measures, Tanner stage, family history or residency (p>0.05). A trend towards higher incidence of consanguineous marriage among families of patients with sickle β-thalassemia was found (p=0.082). Patients with SCA had significantly higher incidence of pulmonary hypertension, acute chest syndrome, frequent sickling crisis, avascular bone necrosis and nehropathy while those with sickle β-thalassemia had higher incidence of splenectomy, viral hepatitits and heart disease (p<0.05). The degree of hemolysis and iron overload was increased in sickle β-thalassemia patients compared with SCA group as shown by elevated transfusion index, LDH and serum ferritin (p<0.05). Patients with SCA displayed an evident state of inflammation, vascular injury and subclinical atherosclerosis reflected by high white blood cells (p=0.018), monocyte count (p=0.017), HbS, sCD163 levels (p<0.001), PMPs (p<0.001) and CIMT (p=0.029). Upon comparing genotypes among patients with mild/moderate versus severe disease, SCA genotype represented the higher incidence in severity (80.8%) followed by sickle βº thalassemia (19.2%) while all patients with sickle β+ thalassemia (n=4) were in the mild/moderate group. Genotype, in addition to HbS and parameters of vascular dysfunction (sCD163, PMPs and CIMT) were independently related to disease severity in logistic regression analysis. The cutoff values the studied vascular markers in relation to disease severity were determined.
Conclusion
Our findings could be of pathophysiological importance, because they provide evidence that genotyping may not only have a role in predicting disease severity in young SCD patients but it is potentially involved in determining the type of vasculopathy developed in those patients, allowing better individualized treatment.
Session topic: E-poster
Keyword(s): Genotype, Pulmonary hypertension, Sickle cell disease, Vasoocclusive crisis
Type: Publication Only
Background
Sickle cell disease (SCD) has a wide spectrum of complications. Many factors contribute to the variability in SCD including genetic determinants.
Aims
To assess the relation between different genotypes among 38 children and adolescents with SCD and vascular markers, iron overload as well as vascular complications and subclinical atherosclerosis.
Methods
SCD patients (21 males and 17 females), in steady state were studied. All patients were subjected to full history and thorough clinical examination with special emphasis on history of sickling crisis, cardiopulmonary disease, acute chest syndrome, stroke, bone manifestations, nephropathy, spleen status, transfusion history and hydroxyurea/chelation therapy. Laboratory investigations included hematological profile, liver and kidney functions, markers of hemolysis (lactate dehydrogenase [LDH] and indirect bilirubin) and serum ferritin. Soluble CD163 (sCD163) was measured by enzyme linked immunosorbent assay while analysis of platelet microparticles (PMPs) was done by flow cytometry. Pediatric SCD severity index was assessed based on both clinical and laboratory variables. DNA genotyping was identified using on polymerase chain reaction and reverse hybridization. Echocardiography and assessment of carotid intima media thickness were performed.
Results
Based upon DNA genotyping, patients were categorized as either homozygous sickle cell disease (HbSS) or heterozygous sickle cell disease (Hb S/β); 24 (63.2%) patients had sickle cell anemia (SCA), 10 (26.3%) patients had sickle βº thalassemia and 4 (10.5%) patients had sickle β+ thalassemia. Comparison between patients with SCA (n=24) and those with sickle β-thalassemia (n=14) revealed no significant difference as regards age, sex, anthropometric measures, Tanner stage, family history or residency (p>0.05). A trend towards higher incidence of consanguineous marriage among families of patients with sickle β-thalassemia was found (p=0.082). Patients with SCA had significantly higher incidence of pulmonary hypertension, acute chest syndrome, frequent sickling crisis, avascular bone necrosis and nehropathy while those with sickle β-thalassemia had higher incidence of splenectomy, viral hepatitits and heart disease (p<0.05). The degree of hemolysis and iron overload was increased in sickle β-thalassemia patients compared with SCA group as shown by elevated transfusion index, LDH and serum ferritin (p<0.05). Patients with SCA displayed an evident state of inflammation, vascular injury and subclinical atherosclerosis reflected by high white blood cells (p=0.018), monocyte count (p=0.017), HbS, sCD163 levels (p<0.001), PMPs (p<0.001) and CIMT (p=0.029). Upon comparing genotypes among patients with mild/moderate versus severe disease, SCA genotype represented the higher incidence in severity (80.8%) followed by sickle βº thalassemia (19.2%) while all patients with sickle β+ thalassemia (n=4) were in the mild/moderate group. Genotype, in addition to HbS and parameters of vascular dysfunction (sCD163, PMPs and CIMT) were independently related to disease severity in logistic regression analysis. The cutoff values the studied vascular markers in relation to disease severity were determined.
Conclusion
Our findings could be of pathophysiological importance, because they provide evidence that genotyping may not only have a role in predicting disease severity in young SCD patients but it is potentially involved in determining the type of vasculopathy developed in those patients, allowing better individualized treatment.
Session topic: E-poster
Keyword(s): Genotype, Pulmonary hypertension, Sickle cell disease, Vasoocclusive crisis
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