Betül Biner

Factor V Leiden Mutation and Other Thrombophilia Markers in Childhood Ischemic Stroke

The aim of this study was to evaluate the association between ischemic childhood stroke and thrombophilia. The prevalence of thrombophilia risk factors in 30 unrelated children with ischemic stroke were compared with 33 age-matched control subjects. Patients and control group were tested for the presence of activated protein C (APC) resistance, antiphospholipid antibodies (APLA), increased factor VIII levels, and for the deficiency of protein C (PC), protein S (PS), and antithrombin. When APCR was detected in patients or in controls, factor V Leiden (FVL) mutation was also tested. Seventeen of 30 patients (56.6%) had at least one thrombophilia marker compared with only 5 of 33 control subjects (15.1%). Three children with ischemic stroke (10%) were affected with a combination of two or more thrombophilia markers whereas none of the children in the control group had a combination of risk factors. Seven of 30 children with ischemic stroke (23.3%) and one of 33 control subjects (3.03%) had APC resistance and in all of them FVL mutation were found. The prevalence of FVL mutation was higher among pediatric stroke patients than among control subjects (p < 0.05). None of the patients but one child from the control group (3.03%) had PS deficiency. Antithrombin and PC deficiencies and the presence of APLA and increased factor VIII levels were more frequent in the pediatric stroke patients than in controls but the difference was not statistically significant (p > 0.05). These data confirm that stroke in children is commonly associated with a combination of multiple risk factors and especially the prevalence of FVL mutation is increased in children with ischemic stroke compared with control subjects.

99mTc-HMPAO Brain Perfusion Single-Photon Emission Computed Tomography in Children with Down Syndrome: Relationship to Epilepsy, Thyroid Functions, and Congenital Heart Disease

In recent years, it has been possible for patients with Down syndrome to live longer with advanced medical treatment and social support. As a result, the problems of these patients, such as thyroid diseases, leukemia, and Alzheimer disease, would be encountered more frequently. In this study, we aimed to perform the brain perfusion of children with Down syndrome by technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) and to determine the relationship between brain perfusion and epilepsy, thyroid function tests, congenital heart disease, and level of mental and motor development. Thirty patients with Down syndrome, aged between 1 and 15 years, were included in our study. Demographic data, the existence of epilepsy and congenital heart defects, the level of mental and motor development, serum levels of thyroid hormones, and autoantibodies were determined. All patients underwent computed tomography (CT) and/or magnetic resonance imaging (MRI). Cerebral SPECT was performed in all cases to evaluate the brain perfusion pattern. According to the visual evaluation of cerebral SPECT results, hypoperfusion was detected in 11 cases (37%). Patients with cerebral hypoperfusion (group 1) and patients with normal cerebral perfusion (group 2) were compared. There was no difference between group 1 and group 2 in terms of demographic data, congenital heart defects, IQ levels, thyroid hormones, and autoantibodies, but the incidence of epilepsy was significantly higher in group 1 (P < .001). When motor and mental development levels were compared, it was found that cases in group 1 were significantly more retarded in personal-social and fine motor skills (P < .05). The present study showed that cerebral hypoperfusion in children with Down syndrome is mostly related to epilepsy and the other coexisting conditions, congenital heart disease and hypothyroidism. Patients with cerebral hypoperfusion also have more retarded developmental levels, especially in personal-social and fine motor skills. (J Child Neurol 2006;21:610—614; DOI 10.2310/7010.2006.00144).

Pitfalls in the Diagnosis of Immune Thrombocytopenic Purpura in Children: 4 Case Reports

Acute idiopathic thrombocytopenic purpura is the most common cause of thrombocytopenia in childhood, and diagnosis of idiopathic thrombocytopenic purpura is made clinically based on the exclusion of other causes of thrombocytopenia. Patients with diverse causes of thrombocytopenia are sometimes erroneously diagnosed as having idiopathic thrombocytopenic purpura. However, for the prevention of misdiagnoses, careful inspection of peripheral blood smear is of utmost importance. This report presents 4 cases presumed as acute idiopathic thrombocytopenic purpura that were finally identified as pseudothrombocytopenia, inherited macrothrombocytopenia (MHY9 disorders) possibly Epstein syndrome, Bernard-Soulier syndrome, and drug-induced thrombocytopenia. They draw attention to the importance of platelet morphology to exclude inherited macrothrombocytopenia and history to exclude drug-induced thrombocytopenia. Better diagnostic approaches would be possible by the awareness of these relatively rare causes of isolated thrombocytopenia.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: a large cohort real-life experience from Turkey (REACH-THEM)

To evaluate the long‐term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion‐dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey.

Factor VIII Levels in Children With Ischemic Stroke

Recently, factor VIII (FVIII) levels were suggested to be high in some adult patients with ischemic stroke and that is thought to be familial. This is not always true for children, however, because there has been no genetic mutation found that led to FVIII elevation (1–3). In our study titled “Factor V Leiden Mutation and Other Thrombophilia Markers in Childhood Ischemic Stroke” (4), published previously in Clinical and Applied Thrombosis/Hemostasis, we argued about the relationship between FVIII levels and ischemic stroke in childhood. We wanted to propose this subject again because there is no consensus about it. This retrospective case-controlled study included 30 children with ischemic stroke who were diagnosed and followed in a single center for mentally and physically handicapped children between January 2000 and December 2002. Neonatal stroke patients and patients presenting with transient symptoms were excluded. The age of the patients was between 1.5 and 15 years (7.1 ± 4.6 years). The definition of ischemic stroke included the presence of an acute thrombotic cerebrovascular event that manifested as hemiplegia, aphasia, visual or balance disturbance, or seizures. In all patients the diagnosis of cerebral ischemic stroke was confirmed by computed tomographic (CT) and/or magnetic resonance imaging (MRI) scans. Thirty-three healthy control subjects from the Pediatrics Outpatient Clinic, ages between 6 months and 15 years (6.8 ± 3.2 years), were enrolled in the age-matched control group. Patients with acute febrile illness, coagulation abnormalities, neurological disease, and chronic inflammatory diseases were excluded. The FVIII level in 30 unrelated children with ischemic stroke has been compared with 33 agematched control subjects. Patients and the control group were tested for the presence of increased factor VIII levels. FVIII activities were measured by the coagulometric assay (Diagnostica Stago, Paris, France). Patients were diagnosed with increased factor VIII levels if its value was > 2 SD of the mean age-adjusted level of control subjects (>200%). Fisher’s exact test was used to compare the prevalence of a combination of factors between patients and control subjects. A P value < 0.05 was considered to be statistically significant. When stroke occurred none of the patients had a condition predisposing to stroke, such as immobilization, sepsis, surgery, dehydration, trauma, or malignancy. Four patients (13.3%) and one control subject (3.03%) were diagnosed with increased factor VIII levels and this difference between groups was not statistically significant (P > 0.05) (Table 1). Recently, new laboratory phenotypes such as high FVIII associated with an increased risk of venous thrombosis have been reported (3). Elevated FVIII is a strong risk factor for recurrence (5). In patients with thrombosis, the high levels of FVIII persist over time and are not caused by acute phase reactions (1,5,6). In the general population, the prevalence of elevated FVIII levels ( 150 IU/dL) is 11%, whereas it has been found in 25 % of patients with a first episode of venous thrombosis (2). In a pediatric thrombosis study of both venous and arterial disease, high levels of FVIII have been calculated to increase the risk of thrombosis approximately 11-fold (7). Although no variations in the FVIII gene associated with high FVIII levels have been identified, FVIII levels tend to show a familial clustering (8). Also, the mechanism between elevated FVIII and thrombosis remains unknown; it is partly mediated through an acquired activated protein C resistance (9). In the present study an increased factor VIII level is not identified to be more common in stroke patients. In addition to this, we found a case with ischemic stroke associated with a combination of