Can STOP Trial Velocity Criteria Be Applied to Iranian Children with Sickle Cell Disease? / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population. Transcranial Doppler (TCD) ultrasound is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We aimed to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes. METHODS: Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) were prospectively recruited from pediatric outpatient clinic over a period of 9 months. We performed TCD in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). RESULTS: Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10+/-4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (P<0.001). The right MCA TAMM (Time Averaged Maximum Mean) was significantly higher than in controls (125+5.52 cm/s vs. 92.5+1.63 cm/s, P<0.001). Left MCA did not show differences. The TICA TAMM was also different between cases and controls (P<0.05). CONCLUSIONS: Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities are higher as compared to healthy controls but appear much lower than those observed in STOP (Stroke Prevention Trial in Sickle Cell Anemia) studies. We hypothesize that some children at high risk may be present with velocities lower than 170-200 cm/s thresholds. A prospective validation of ethnicity-specific prognostic criteria is warranted.

Tissue doppler echocardiographic findings of left ventricle in children with sickle-cell anemia

Sickle-cell disease [SCD] is an inherited hemoglobin childhood disorder, frequently complicated by pulmonary hypertension and cardiac involvement. Cardiovascular events and complications are the leading cause of mortality and morbidity in patients with SCD. Tissue Doppler imaging and the myocardial performance index [Tei index], are simple indices for the assessment of the cardiac function. The purpose of this study was to assess the left ventricular function in children with SCD. Sixty-four patients with SCD [mean age = 11.7 +/- 5.5 years] were compared with 50 age matched healthy controls [mean age = 11.2 +/- 5.20 years]. Myocardial wall motion velocities at the lateral mitral annulus and the junction between the medial mitral annulus and the interventricular septum were assessed during systole [Sa], early diastole [Ea], and late diastole [Aa] through a four-chamber view using pulsed Doppler echocardiography. The ejection fraction and shortening fraction were estimated. The Tei index was estimated via tissue Doppler echocardiography. The results showed that Ea and Aa velocity in the mitral annulus and interventricular septum had no difference between the patients and controls [p value > 0.05], and nor was there any difference between the two groups as regards the Tei index, Ea/Aa, ejection fraction, and shortening fraction [p value > 0.05]. Sam wave velocity, however, had a significant difference between the two groups [p value < 0.038]. The Tei index is a sensitive indicator for the cardiac function in chronic diseases and the right ventricular function in some disorders such as SCD

Combined and alternative iron chelator drugs in treatment of thalassemia major

To assess the efficacy and safety of the sequential deferoxamine [DFO] and deferasirox/Osveral [OSV] [[Seq OSV/DFO]] protocol and combinations of Deferroxamine/ Deferiprone [Com DFO/DEF] in thalassemia major [TM] patients. A total of 148 male and 142 female patients of thalassemia major [TM] were enrolled in these studies. Out of 290 patients sixty two [31 male, 31 female] aged 6 to 30 years [mean: 18.5] entered into Seq OSV/DFO study and 228 TM [117 male, 111 female] aging 2 through 36 years [mean: 17] were eligible for Com DFO/DEF trial. Seq OSV/DFO was a regimen consisted of four days Osveral followed by three days deferoxamine and Com DFO/DEF was a protocol of DEF seven days a week, along with DFO of a minimum of two to four nights per week The duration of trial was six months. The efficacy was determined by comparison of pre and post treatment ferritin and safety was assessed by frequency of adverse drugs reaction [ADR]. For both regimens serum ferritin declined significantly and compliance response was excellent. During trials 33.8% and 21% of patients experienced at least one ADR for combination and sequential respectively. Deferoxamine [DFO] /deferasirox [OSV] and Deferroxamine/Deferiprone[DEF] are acceptable regimens with high efficacy, low toxicity and excellent compliances

new valid formula in differentiating iron deficiency Anemia from beta thalassemia trait

To compare the validity of a new index [HbxRDWx100/ [RBC] 2xMCHC] with twelve discriminating functions [DFs] to differentiate iron deficiency anemia [IDA] and beta-thalassemia trait [beta-TT]. A total of 823 patients [317 IDA and 506 beta-TT] aged 15 to 35-year-old were enrolled in this study. The diagnostic sensitivity, specificity and other validity parameters were calculated to assess the diagnostic reliability of the novel index [Keikhaei index [KI]] vis-a-vis the other published DFs [Mentzer Index [MI], Green and King Index [G and KI], red cell distribution width index [RDWI], England and Fraser Index [E and FI], Bessman and Feinstein index [B and FI], Telmissani et al index [TI], Srivastava and Bevington index [S and BI], Shine and Lal index [S and LI], Ricerca et al index [RI], Ehsani et al index [EI], Sirdah et al index [SI], and Red Blood Cell Count [RBC] were calculated in all patients. All thirteen DFs didn't have the sensitivity and specificity of 100%. The KI, RDWI, G and KI and E and FI showed the most sensitivity and specificity for both IDA and TT; moreover, the lowest reliable indices belonged to B and FI, S and LI and RI. According to Youden's index [YI], DFs in the order of highest to lowest were KI>G and KI>RDWI>E and FI>RBC>M I>EI>TI>SI>S and BI>RI>S and LI>B and FI

Serum zinc level in thalassemia major

To compare serum zinc level between Thalassemia Major [TM] patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine [DFO] and 31 were on the combination of DFO and deferiprone [DEF] protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15 +/- 5years. Mean serum zinc level was 68.97 +/- 21.12microg/dl, 78.10 +/- 28.50 microg/dl, and 80.16 +/- 26.54 microg/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran

Evaluation of pulmonary function in beta-thalassemia major patients

To describe and quantify the functional change of the lung in patients with beta-thalassemia major [TM] and determine the correlation between pulmonary function test [PFT] results with hemoglobin, ferritin and age changes. Pulmonary function tests were performed on 60 transfusion-dependent patients with TM, ranging in age from 10 to 45 years. Percent-predicted values for forced expiratory volume in one second [FEV1], and forced expiratory flows [FEF] 25-75% were significantly reduced, whereas forced expiratory vital capacity [FVC] and FEV1/FVC were closed to normal limits, indicating a restrictive disease. All factors including; FVC, FEV1, and FEV1/FVC, FEF 25-75% were negatively correlated with age and ferritin levels. In contrast, all factors including; FVC, FEV1, and FEV1/FVC, FEF 25-75% were positively correlated with hemoglobin [Hb]. We performed linear regression analysis to study the simultaneous influence of the presence of age, ferritin, and Hb on obstructive PFT indexes. Pulmonary function test results were normal in only 32 [53.3%] of 60 patients and the rest 28 cases [46.7%] showed abnormal pulmonary function. FEV1 and FEF25%-75% have significant negative correlation with age [r=- 0.64 p[r]=0.003 and r=- 0.58 p[r]=0.02 respectively], also have significant positive correlation with Hb [r=0.31 p[r]=0.015 and r=0.33 p[r]=0.01 respectively], and only FEF25%-75% has significant negative correlation with ferritin [r=-0.26 p[r]=0.04]. The present study has shown that restrictive disease and reduced lung diffusing capacity are the predominant abnormalities of pulmonary function in patients with TM. The low hemoglobin concentration and a fall in the diffusing capacity of the alveolar-capillary membrane, together with the dependence of the reduced pulmonary diffusing capacity on age and serum ferritin levels, as well as of the entity of restrictive disease on age, suggests that pulmonary dysfunctions in patients with TM are due mainly to lung fibrosis and/or interstitial edema related to iron overload

Cord compression due to extramedullary hematopoiesis in two patients of beta -thalassemia intermedia

Thalassemia is the most important hemoglobinopathy in Khuzestan province. Thalassemia intermedia [TI] is a genetically heterogenous disease and can result from many different genetic lesions. We report two cases of TI-EMH caused by two separate mechanism and their successful management. Magnetic Resonance Imaging [MRI] is the best diagnostic method in these cases. Management can be done via: Transfusion therapy, Radiotherapy, Hydroxyurea [HU], and Surgery. A 17 years old girl with beta-TI previously asymptomatic presented with back pain and leg weakness which started one month ago. The other patient was 25 years old man referred to hospital with back pain, paresthesia, urine frequency and impairment of gait. In the first case the cause of cord compression was the osseous expansion while in the second patient it was related to soft tissue EMH. First patient was successfully treated with low dose radiotherapy and HU. Radiotherapy was initiated with 200cGY fractions to a total dose of 1600cGY and HU 10mg/kg/day. At the end of radiotherapy, the patient was ambulatory with mild residual weakness. She was regularly followed for two years; at present she is active and asymptomatic. The second patient was successfully treated with low-dose radiotherapy and HU. Radiotherapy was started in 200cGY fractions to a total dose of 1600cGY and HU was given at 10mg/kg/day. At the end of radiotherapy the patient was ambulatory with mild residual weakness. He was regularly followed for six months. At his last visit, he was able to walk and climb stair without any assistance. His neurological examination was much better than before. The most common site of spinal epidural extramedullary hematopoiesis is the posterior aspect in the thoracic spine. EMH can be prevented by regular transfusion therapy which corrects anemia and thereby abolishes the stimulus for EMH. Surgical decompression is the method of choice for the management of EMH because histological diagnosis can be established and immediate decompression of the mass can be achieved. This is especially important to decompress the spinal cord quickly in patients with epidural mass caused by EMH. The disadvantages of surgical intervention include risk of excessive bleeding due to high vascularity of the mass and higher incidence of recurrence. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with an intrathoracic mediastinal mass