الفهرس 
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Abstract
Sickle cell disease (SCD) is a group of recessively inherited hemoglobinopathies. The clinical manifestations result primarily from hemolytic anemia and the effects of repeated vasoocclusion and ischemic injury that may affect almost every organ and can lead to considerable morbidity and mortality . Selectins are a family of cell adhesion molecules . Interactions between sickle reticulocytes, leucocytes,platelets and endothelial cells via these adhesion molecules occur in patients with SCD and may contribute to disease pathology . The aim of this work is to study changes in plasma P-selectin level in children patients with sickle cell anemia and sickle thalassemia . This study was conducted on two groups, the patient and the control group. 1- the patients group: Consisted of 30 patients, 15 females and 15 males who were previously diagnosed as having sickle cell anemia(12 patients) and sickle thalassemia (18 patients) . Most of our patients were out patients visiting the hospital with simple conditions or for follow up and blood transfusion ‘if needed’, 4 were admitted for VOC, ACS, hemolytic crisis and strcke. Patient group age ranged from 2 -16 years with a mean of 8.8 ± 4.9 years and median age of 7.8 years. 2-the controls group: Consisted of 20 normal children and adolescents, 10 females and 10 males of comparable age,sex,and socioeconomic standared.Their age ranged from 4-12.6 years with a mean of 8.5±4.1 years and median age of 7.5 years . All cases were subjected to the following: 1- Full history taking . 2- Thorough clinical examination . 3-Laboratory investigations: a-CBC. b- Plasma P-selectin level. In our study, there was no significant difference between patients and control group regarding age and gender. Both males and females were affected in nearly equal ratio. This is consisted with the autosomal mode of inheritance of SCD. There was highly significant difference between patients and control group regarding family history of SCD. +ve family history was found in 22 cases out of 30(73.3%), while no family history was found in families of the control group as any child with +ve family history of SCD was excluded. Consanguinity was highly significantly higher in patients than controls. It was +ve in 20 out of 30 families of the patients group(66.7%), while it was +ve in 4 out of 20 families of the control group(20 %). This is consistent with the recessive nature of the disease where consanguineous marriage between carriers will increase the incidence of the disease in the offsprings. The age of 1st presentation of SCD in our patients ranged from 3 months to 6 years old usually by vaso occlusive episodes, pallor or fever. This is confirmed by the fact that newborn with SCD is not generally anemic and is asymptomatic because of the protective effect of Hb F. After the 1st few months of life, as βs-globin production increases and HbF declines, the clinical symptoms of sickle cell anemia emerge. The clinical features of SCD and age of 1st presentation are extremely variable, due to complex interactions with many modulators of disease phenotype, including genetic and enviromental factors . In our study we found that mean hemoglobin level was significantly lower in patients than controls ,with a mean of 7.25 ± 1.42 (g/dl) in patients in contrast to 10.88 ± 1.32 in controls due to the chronic hemolytic nature of sickle cell anemia . we found no correlation between sp-selectin level and age of patien, age of 1st presentations of SCD, Gender, Consanguinity, Family history nor frequency of blood transfusion. In our study 7 patients (23.3%) were Splenectomized with a mean age of surgery 5.9±1.6 years. Causes of splenectomy were huge spleen, trauma to huge spleen, sequestration crisis and hypersplenism. It is predicted that platelet counts increases after splenectomy and so increase level of sp-selectin they produce, but in our study we found no correlation between sp-selectin level and surgical Splenectomy or age of the surgery. Regarding treatment, 20% of our studied patients were on hydroxyurea, 16.6% were on desferioxamine, 63.3% received neither of them. All our patients were on the standard treatment (calcium-vitamin D-piracetam-folic acid-L-Carnitine-vitamin B) . In our study we found no correlation between sp-selectin level and hydroxyurea usage. Platelet count and sp-selectin level were highly significantly higher in our patients than controls. A positive significant correlation between sp-selectin level and platelet count was found. We found that there was no correlation between sp-selectin level and Vaso-occlusive episodes. Most of our patients were outpatients visiting the hospital with simple conditions or for follow up and blood transfusion if needed,few were admitted for VOC,ACS, hemolytic crisis and strock. Platelet count and sp-selectin level were elevated in all of them nearly to the same extent. This diffeance in results between our results and results of other studies ,as we found that there was no correlation between sp-selectin level and vaso-occlusive episodes, or organs affection as Hepatosplenomegally may be attributed to that some of our patients who were in vaso occlusive episodes were on hydroxyurea which is thought to decrease expression of cell adhesion molecules. We acknowledge the limitation of our sub-analysis of severity to the small numbers of the studied group. sP-selectin is crucial in modulating leukocytes,platelets and endothelial cells adhesion during inflammatory response and thrombus formation. So as expected in SCD which is a chronic inflammatory and hypercoagulable state , WBC count was highly significantly higher in our patients than controls.We found a positive strong correlation between spselectin level and WBCs count CRP level was highly significantly higher in our patients than controls .We also found a positive strong correlation between sp-selectin level and CRP level. Serum ferritin is a widely available and cost-effective screening test for iron overload but can be unreliable in SCD due to the inflammatory nature of the condition, even in the steady state as ferritin is an acute-phase reactant. In our study serum ferritin level was significantly higher in our patients than controls. We found no correlation between sp-selectin level and serum ferritin level Regarding hemoglobin types, in our study we found that there was a negative correlation between HB A and sP-selectin level, no correlation between HB A2 and sp-selectin, no correlation between HBF and spselectin and positive moderate correlation between HBS and sp-selectin. We found no statistically significant difference in sP-selectin level in the 2genotypes Hb SB and Hb SS as well. SO we think that sp-selectin level in SCD is not affected by a single factor. Hydroxyurea, spleen, hemoglobin types and their level, medical condition at time of sample collection,CRP,organ dysfunction and even regularity in taking medications may all be key players affecting its level, factors overlap . So to judge the correlation between sp-selectin level and any other variant,2 groups similar in every thing except this variant should be examined . We concluded that the most significant predictors for sp-selectin level change are platelet and WBCs count. from this study we can recommend that: 1-Great care should be given to this vulnerable group of patients through regular follow up visits and by such preventive measures as vaccinations and penicillin prophylaxis. 2- Psychological support to these children and their families . 3-Patients and parents education about the chronic disease nature, how to deal with mild conditions,when to consult, importance of genetic counseling, follow up and regular treatment intake. 4- As we found increased plasma level of sP-selectin which is an evidence of platelet activation ,a key components in many pathophysiological changes in sickle cell disease , more researches on larger number of patients are needed to study using P-selectin as a marker for predicting vaso pathology in SCD, so early intervention may be done to prevent these VOC, and the potential utility of plasma levels sp-selectin to identify high-risk patients merits further investigation and short intervals follow up. 5- Researches should be done to search for useful therapeutic agents capable of antagonizing p-selectin that may alleviate disease severity.