الفهرس 
SICKLE CELL DISEASEOnly 14 pages are availabe for public view
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Abstract
S
ickle cell disease (SCD) is a hematological inherited disorder that have multiple-system involvement. Major pathobiological processes for SCD are HbS polymerization, vaso-occlusion, hemolysis-mediated endothelial dysfunction and sterile inflammation.
Vascular complications of sickle cell disease can be divided into two main groups: those caused by large vessel vasculopathy (cerebrovascular disease, pulmonary hypertension, priapism and leg ulcers) and those caused by vaso-occlusive ischemic events leading to painful episodes and progressive organ damage (hyposplenism, osteonecrosis, retinopathy, nephropathy, acute chest syndrome and liver damage).
Prior studies have described that VEs are associated with poor outcomes in the short term and decreased quality of life in patients over the long term.
The main aim of our study was to evaluate the circulating CD34 as a novel predictive marker of occurrence of peripheral vascular event in children with sickle cell disease in their steady state and relate their levels to number(s) and type(s) of VEs in the following 6 months.
CD34 is considered as a cell surface marker that is expressed by a broad range of cells including hematopoietic, stromal, epithelial, and endothelial cells. Although the function of CD34 as a surface antigen is still unknown, it has been linked to inhibition or facilitation of adhesion, cell proliferation, and regulation of differentiation.
This study was an exploratory study, conducted at Pediatrics hematology-oncology unit at Ain Shams University Children’s Hospital, where 50 children with sickle cell disease were enrolled at their steady state, aged 6 months - 16 years. Flow cytometry was done for quantification of circulating CD34+ at inclusion and compared to age and sex matched control. And patients were followed up for 6 months for vascular events.
In our study, patients who developed peripheral vascular events on follow up has statistically significant higher level of previous neurovascular events, previous peripheral vascular events and previous history of VOC with p-value 0.015, 0.001 and 0.001 respectively.
There was significantly higher percentage TLC, neutrophil count, platelet count and CD34+ in patients with peripheral vascular events after 6 months of follow up with p-value 0.015, 0.008, 0.042 and 0.022; respectively.
Our study revealed significant higher level of CD34+ among sickle cell disease patients compared to age and sex matched control with p-value <0.001 as well as statistically significant higher level of CD34 among patients who developed vascular events on follow up compared to those who did not suffer from vascular events with p-value 0.022.
In this study there was no statistically significant difference found between patients with and without peripheral vascular events after 6 months of follow up regarding liver size by US, pulmonary pressure by TRV and R.TAMMAX by TCD at steady state except L.TAMMAX was significantly higher in those with peripheral vascular events after 6 months of follow up than those without with p-value 0.028.
The multivariate logistic regression analysis by backward (Wald) method shows that the most important factors associated with occurrence of vascular events after 6 months of treatment were CD34+ >4340 with p-value = 0.003 followed by type of transfusion with p-value = 0.016.
There is statistically significant positive correlation found between CD34+ and TLC, neutrophils, lymphocytes, PLT, uric acid, retics, T.bilirubin, and albumin/ creat ratio in urine with p-value 0.001, 0.001, 0.002, 0.044, <0.001, <0.001, <0.001 and 0.012.
There is also significant positive correlation found between CD34+ and right TAMMAX at follow up with p-value 0.004.
However no statistically significant correlation found between CD34+ and initial Hb electrophoresis S, F, Serum ferritin, LDH, PT, INR, PTT and Plt-leukocytic complex with p-value 0.063, 0.329, 0.057, 0.261, 0.411, 0.389 and 0.967.
There is statistically significant correlation between CD34+ and peripheral vascular events and VOC after 6 months of follow up with p-value 0.022 and 0.022; respectively.
Receiver operating characteristic curve (ROC) for CD34+ level to differentiate between patients with and without vascular events after 6 months of treatment showed that shows that the best cut off point between patients with and without vascular events after 6 months of treatment regarding CD34+ level was found >4340/ml with sensitivity of 62.07%, specificity of 85.71% and area under curve (AUC) of 0.691.
Conclusion:
CD34+ cell count appears as a promising marker of peripheral vascular event occurrence in children with SCD. A large prospective study including CD34+ count with a longer duration of follow up of patients with SCD is needed to validate these findings.