Prevention and management of stroke in sickle cell disease

Sickle Cell Disease(SCD) is one of the most common hemoglobinopathies in the world which causes stroke. The management of stroke depends on the manifestations and the age of the patient. Especially in childhood, anatomic and physiological abnormalities of CNS may be a predisposing factors. Stroke mostly affects the distal segments of the Internal Carotid Artery, but also middle and anterior segments of the cerebral arteries are involved. The most important predisposing factors are the arterial malformations, stenosis and obstructions in cranial arteries, generally involving Internal Carotid Artery, frequently Proximal Middle Cerebral or Anterior Cerebral Arteries. After infarcts at brain vessels, most frequent clinical findings are hemiparesis or hemiplegia, impaired speech, focal seizures, gait disturbances. Risk factors for predisposing stroke are prior transient ischemia, baseline Hb decrease, acute chest sydrome within previous two weeks, systolic blood pressure rises, leucocyte increases. The patient with silent stroke or transient ischemic attacks may be asymptomatic or without neurological symptoms. Neuroimaging abnormalities may be seen without significant clinical findings in children with SCD. We talk about silent stroke if there are neuroradiological abnormalities without clinical findings. Children with silent strokes are more prone to new strokes. If there is a significant stroke a ischemic stroke often present with focal neurological signs and symptoms. If patient is asymptomatic or have suspected stroke, first step may be performance of Transcranial Doppler Ultrasonography (TCD). Children with time-averaged mean velocity (TAMV), measured in Middle Carotid Artery or in distal internal carotid Artery abnormally elevated, defined as TAMV&ge;200cm/sec, have sixfold increase for stroke than those with normal TAMV&le;170cm/sec. For these patients under the risk of stroke, chronic blood transfusion is recommended for prevention of primary stroke events. Because of high oxygene demand in children, the child with SCD who also has anemia is at particular risk. The management of acute stroke includes to rule out hemorrhage, stabilize vital signs, careful use of hydration and RBCs transfusion. Exchange blood with normal RBCs is mandatory; it will improve tissue perfusion and oxygenation. Long-term management of stroke is directed to prevent recurrences with fluids supplementation, a chronic transfusion programme at least for 6 months with exchange transfusion or erythrocytapheresis for reducing the HbS under 30%. After 3 years of HbS levels to be maintained &lt;30%, the HbS leveles can be raised safely to less than 50% if the patient has remained neurologically stable. Indefinite chronic transfusion programme was advised for the patients with abnormal TCD values. Hydroxyurea (HU) is an alternative therapy in reducing TCD values and to try to increase HbF improving the clinical outcome. Periodical cranial Doppler ultrasound examination and selective red blood cell transfusions &lsquo;d be useful for stroke prevention.&nbsp;镰状细胞病(SCD)是世上最常见的血红蛋白病，可致中风 中风防治受症状表现和病人的年龄所左右。 尤其对于患儿，中枢神经系统的组织异常和生理异常可能是诱病因素。 中风通常影响颈内动脉的末端，但也会牵连到脑动脉的中段和前段。 中风最重要的诱病因素有动脉畸形、器官狭窄和大脑动脉阻塞，一般和到颈内动脉有关，但牵连到大脑中动脉或大脑前动脉更为常见。 脑血管梗塞后，通常临床发现轻偏瘫或偏瘫、语言障碍、病灶性颠痫和步态障碍等。 诱病性中风具有的风险包括：前两周内引起短暂性局部缺血、血红蛋白含量减少和急性胸痛综合症，然后导致收缩压升高和白血球增加。 轻度中风或短暂性脑缺血发作的患者可能无症候或无神經症狀。 在没重大临床发现的情况下，镰状细胞病患儿可做脑神经成像检查，异常亦会发现。 下边我们将讨论无临床表现情况下神经放射性异常。 轻度中风的患儿再次中风的可能性很大。 如果中风严重，脑缺血的出现经常伴随着局部性神經系統症候和症状 如果患者无症候或疑似中风，首先应进行经颅多普勒超声（TCD）检查。 在异常抬升的中动脉或内动脉末端测量时间平均血流速度(TAMV)，结果为TAMV&ge;200cm/sec，该患者中风的可能性是正常情况（TAMV&le;170cm/sec）的六倍。建议对有中风危险的患者采取慢速输血的方法，以防止主要中风事件。 由于儿童对氧的需求量高，患镰状细胞病同时伴有贫血的儿童危险系数尤其高。 急性中风防治的措施包括：排除溢血的可能性、稳定生命体征、谨慎利用水和作用和（血红细胞）RBCs输血 必须使用正常的RBCs交换血液；提高组织灌注和氧化作用。 中风的长期防治旨在阻止再次补充液体，用交换输血或红细胞除去法慢速输血至少6个月，以便把血红蛋白含量减少到30%以下。 血红蛋白含量&lt;30% 保持3年后，如果患者神经稳定，可将其升高到50%以下。 TCD值不正常的患者，建议采取不定期慢速输血程序。 作为降低TCU值的备用疗法，羟基脲（HU）尝试提高HbF的含量，达到改善临床结果的目的。 防止中风有效的措施包括定期对大脑进行多普勒超声检查和有选择性的进行血红细胞输血。</p

Hemoglobinopathies in Turkey

[No abstract available

Plasma, erythrocyte and urinary selenium levels in sickle cell homozygotes and traits.

PubMedID: 8249189Plasma, erythrocyte and urinary selenium levels were determined in 21 sickle cell homozygote patients, 20 siblings with sickle cell traits, 29 parents and in 21 healthy controls with an HbAA pattern. The mean levels of plasma and erythrocyte selenium and the daily urinary selenium depletion were found to be lower in the HbSS patients than in the controls (p 0.05). The mean erythrocyte selenium levels were found to be decreased in the parents as compared with the controls (p < 0.05), which indicates that urinary selenium losses may be replenished primarily by sources in the plasma and in the erythrocytes before stores in the other parts of the body are used

Natural coagulation inhibitors (protein C, protein S, antithrombin) in patients with sickle cell anemia in a steady state

PubMedID: 11737735Background: Patients with sickle cell anemia (SCA) run the risk of having decreased levels of natural coagulation inhibitors. This may be due to either hemostatic abnormalities or hepatic dysfunction. This study is designed to evaluate coagulation profiles of patients with SCA in a steady state and to determine whether hypercoagulable state is present or not. Methods: Seventeen children with SCA in a steady state were included in this study. The routine hematological evaluation was done with a coulter-counter. Reticulocyte percentage and blood coagulation tests were also determined. The coagulation inhibitors such as protein C (as activated partial thromboplastine time prolongation time), protein S (as Factor V inhibition) and antithrombin (colorimetric assay) were measured in all cases. Results: In the coagulation profile, mean euglobuline lysis time and mean fibrin degradation product levels were both significantly higher in the patient group than in the control group (P < 0.05), although other parameters were within normal limits. The values for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and indirect reacting bilirubin were significantly higher in the patient group than in the control group (P < 0.001, P < 0.005, P < 0.0001, respectively). The serum protein levels were normal. Mean factor V level was significantly lower and mean factor VIII level was found significantly higher in the patient group than in the control group (P < 0.05 and P < 0.005, respectively). Protein C and AT levels were lower in patients with SCA than in control subjects (P < 0.001). Protein S levels were also lower in the patient group than in the control group, but the difference between the two groups was not significant (P < 0.05). Conclusion: It is indicated that antithrombotic functions of patients with SCA are handicapped even in a steady state; and both hemostatic abnormalities and hepatic dysfunction contribute to low levels of natural coagulation inhibitors

Modeling of voltage output charge-pump phase frequency detector in tuning loops

Resonant inverters mostly employ tuning loops based on a phase-locked-loop (PLL) circuit. Some commercially available PLL chips, frequently used in this application, include a voltage output charge-pump phase frequency detector (CP/PFD) rather than well-known current output CP/PFD, which complicates the analysis of the loop. We present a new model for voltage output CP/PFD and an analysis of a tuning loop using this model. The proposed model employs the resistance multiplication approach, which is applicable for the circuits containing periodically operated switches. It is shown that a voltage output CP/PFD in conjunction with a simple RC low-pass filter can be modeled using a dc voltage source, a phase error controlled resistor, and a capacitor. The theoretical study is verified by experimental results

Thyroid functions in mild and severe forms of sickle cell anemia

PubMedID: 8942004In the present study, the weight, height, bone age and growth indices of 24 children with homozygote sickle cell anemia were measured and the relationship of these parameters to thyroid function was evaluated and compared with 14 healthy controls in the same age group. The patients consisted of two groups with either mild (n = 12) or severe (n = 12) clinical courses. There was no difference between both patient groups or with the control group with respect to weight (P > 0.05). However, the difference between the mean height percentiles of the homozygote-severe group and the control group was found to be statistically significant (P 0.05). These results show that patients with severe clinical courses may have short stature but their thyroid hormones are within normal limits during the first decade of life. 1996 Japan Pediatric Society

Vascular endothelial growth factor levels in childhood acute lymphoblastic and myeloblastic leukemia

Angiogenesis has been associated with the growth, dissemination and metastasis and has been shown to be a prognostic. Although there are some data suggesting that angiogenesis may have a role in the pathophysiology of leukemia, its role in patient prognosis is yet to be defined. We analyzed the expression level of vascular endothelial growth factor (VEGF), an angiogenesis promoter and its possible- prognostic value in bone marrow samples at the time of diagnosis and remission of acute childhood leukemia patients. Besides 46 patients diagnosed as ALL or AML, 16 children were also included as a control group in the study. Our data have demonstrated that VEGF levels of AML patients were found higher than the control group statistically (P = 0.022). However we could not find any significant difference between VEGF levels of diagnosis and remission in both AML and ALL groups by blastic VEGF expression (P > 0.05). In this study the higher levels of VEGF in AML patients is one of the main findings although we were not able to assess any role of VEGF in predicting prognosis in pediatric leukemia patients by evaluating blastic cell VEGF expression. These results have demonstrated that the relationship between angiogenesis or angiogenesis promoters and hematological malignancies is not clear and simple as different methods or different cells beside different angiogenesis promotors are involved to these studies. So that not only tumor cells and their cytokines but also surrounding cells and their cytokines must be taken into consideration with the standardized study methods in the further studies to obtain a promising treatment approach. © 2011 Indian Society of Haematology & Transfusion Medicine