Some predisposing factors for stroke in children with sickle cell anemia

ABSTRACT

This study was done to detect cases of silent and clinically overt strokes in children with sickle cell anemia [SCA] either in the steady or thrombotic crisis states as well as to evaluate the role of some laboratory and genetic parameters as predisposing factors for development of stroke including fibrin peptide-A [FPA], thrombinantithrombin 111 complex [TAT], fibrin degradation products [D dimer], platelet endothelial cell adhesion molecule-l [PECAM-1] and molecular genetic study of the angiotensin converting enzyme [ACE] gene polymorphism. The study included 20 children with SCA diagnosed clinically, hematologically and confirmed by hemoglobin electrophoresis. They were divided into two groups, group I; included 10 children with SCA in steady state and group PI; included 10 SCA children in thrombotic crisis. Another 10 healthy children with matched age and sex were taken as a control group. All the studied groups were subjected to full clinical examination, measurements of FPA, TAT, D-dimer and PECAM-1 as well as molecular genetic study of the ACE gene polymorphism. Brain computed axial tomography [CT] scan and/or magnetic resonance imaging [MRI] as well as electro-encephalographic studies [EEG] were done only for patient groups. Results showed that silent ischemic brain infarction evidenced only by CT scan and/or MRI was present in one patient in group I [10%] and one patient in group II [10%]. On the other hand, two patients in group II [20%] were presented by clinically overt strokes. Thus, according to the presence or absence of stroke either silent or clinically overt there were stroke group [4 children] and non-stroke group [16 children]. Laboratory results showed that the levels of FPA, TAT, D-dimer and PECAM-1 were significantly elevated in SCA patients both in the steady and crisis states as compared to control, with more evident significant elevation in group I1 [thrombotic crisis] as compared to group I [steady state]. Stroke group showed significant elevation in all the studied parameters; FPA, TAT, D-dimer and PECAM-1 as compared with non-stroke group. The molecular study results showed that the frequencies of both DD genotype and D allele of ACE gene in the thrombotic crisis were significantly higher than in the control group and that all stroke group children are of DD genotype. In conclusion; significant increase in FPA, TAT, D-dimer and PECAM-1 levels as well as the presence of ACE D allele of the ACE gene are significant predisposing factors for stroke in children with SCA either in the steady or in the crisis states which may recommend regular follow-up by thorough neurological examination and neuro-imaging studies for early detection of silent brain infarction as well as the preventive use of effective therapies as repeated blood transfusion and bone marrow transplantation