The effect of ferritin levels on distal femoral cartilage thickness in patients with beta thalassaemia major.

INTRODUCTION: To the best of our knowledge, the present study is the first in the literature to assess distal femoral cartilage thickness and its relationship with ferritin levels in adult patients with beta thalassaemia major (BTM). MATERIALS AND METHODS: 45 patients with BTM and 45 healthy controls were included in the study. Ferritin and haemoglobin levels of the patient and healthy groups were determined by blood analysis and distal femoral cartilage thicknesses were measured via ultrasound. Then, the patient group was divided into subgroups according to whether their ferritin levels were below or above 2500 µg/L. They were then compared among themselves and with the healthy control group using the available data. RESULTS: Distal femoral cartilage thickness values were statistically significantly lower in the BTM group compared to the healthy control group (p values < 0.001). Patients with a ferritin level below 2500 µg/L had statistically significantly higher right and left average distal femoral cartilage thickness values than the patients with a ferritin level above 2500 µg/L (p = 0.029 and p = 0.019, respectively). The right and left average distal femoral cartilage thickness values of the patient subgroup with low ferritin levels were statistically similar to the control group (p = 0.146 and p = 0.164, respectively). CONCLUSION: Our study showed that thalassaemia patients are more likely to develop osteoarthritis (OA) than the normal population and possible OA development can be prevented by keeping the ferritin levels of these patients in the optimum range.

Associations Between Transcranial Doppler Flow Velocities, Laboratory Parameters, and Clinical Features in Turkish Children With Sickle Cell Disease.

OBJECTIVE: Stroke is one of the major complications of sickle cell disease (SCD). Stroke features either occlusion of, or stenosis at, the origin of one of the large intracerebral arteries, the internal carotid artery (ICA), and/or the middle cerebral artery (MCA). PURPOSE: We sought correlations between cerebral blood flow velocities and the laboratory and clinical findings of patients with SCD. MATERIALS AND METHODS: Fifty-three pediatric SCD patients (39 with HbSS, 14 with HbSß0) were analyzed. The mean patient age was 12.9±3.9 years. The control group contained 24 healthy individuals. The time-averaged maximum mean velocity (TAMMV) and resistive index (RI) of the MCA, the TAMMVs of the ICA and vertebral artery (VA), and the diameter of the VA were estimated through transcranial Doppler ultrasonography using a 2.5 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. We evaluated the relationships between the TAMMVs, laboratory parameters, and clinical findings. RESULTS: The mean±SD MCA TAMMV was 161.2±35.4 cm/s in patients with HbSS and 185.8±62.9 cm/s in patients with HbSß0. The mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 168.5±43.9 cm/s, 0.63±0.06, 116.8±25.5 cm/s, 69.2±18.5 cm/s, and 3.5±0.61 mm for all SCD patients, respectively. In the control group, the mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 103.8±28.8 cm/s, 0.53±0.04, 96.4±27.8 cm/s, 40.3±12.1 cm/s, and 3.4±0.6 mm, respectively. Although the differences were not significant, TAMMVs were higher in HbSß0 patients taking hydroxyurea; those with hemoglobin levels <8 g/dL, ferritin levels >1000 ng/dL, mean platelet volume >12 fL, or red cell distribution width >18%; or required chelation, or were below the third percentiles of weight and height. The TAMMV was significantly higher only in SCD patients who complained of headache. CONCLUSIONS: High ferritin and low hemoglobin levels, a high mean platelet volume, a high red cell distribution width, low weight (below the third percentile), and a short height (below the third percentile) may be associated with elevated cerebral blood flow velocities and an increased stroke risk in children with SCD. Children with such features should be closely followed-up through transcranial Doppler ultrasonography examination.

Evaluation of sleep quality and restless legs syndrome in adult patients with sickle cell anemia.

PURPOSE: To determine the prevalence of poor sleep quality and RLS in adult patients with sickle cell anemia (SCA). The second aim was to identify the risk factors for RLS and impairment of sleep quality in SCA patients. MATERIALS AND METHODS: Patients at least 18 years old, with hemoglobin electrophoresis confirmation of sickle cell disease, were included. Restless legs syndrome was diagnosed according to the International Restless Legs Syndrome Study Group criteria. The sleep quality of the patients was determined using the Pittsburgh Sleep Quality Index (PSQI) scale. The Epworth Sleepiness Scale (ESS) was used to assess excessive daytime sleepiness. RESULTS: Of 72 patients enrolled in the study, the median total PSQI score was 5 (R 1-17). The total PSQI score was significantly associated with increased age and number of acute severe or extremely severe painful crises during the previous year (p < 0.001, r = 0.45; p = 0.013, r = 0.291 respectively). Of 72 patients, 13 (18%) had RLS and 11 (15%) had excessive daytime sleepiness. The presence of RLS was significantly associated with increased age (p = 0.004). The presence of RLS was not associated with fetal hemoglobin, hemoglobin, hematocrit, or ferritin levels (p > 0.05 for all). CONCLUSION: The prevalence of RLS among this sample of adult patients with sickle cell anemia was much higher than that previously reported for the general Turkish population. The presence of RLS was an important cause of sleep disturbance in these adult patients with SCA.

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

OBJECTIVES: 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. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.

Mean Platelet Volume can Predict Cerebrovascular Events in Patients with Sickle Cell Anemia.

OBJECTIVE: The purpose of this study was to determine the impact of mean platelet volume (MPV) on the frequency and severity of vaso-occlusive and cerebrovascular events in patients with sickle cell anemia (SCA). METHODS: The 238 cases diagnosed with SCA were evaluated retrospectively with respect to the occurrence of painful crisis for the previous year. The incidence, severity and type of the vaso-occlusive crises of the patients with SCA between March 2010 and March 2011 were recorded. The last MPV values in patients who were free of erythrocyte transfusion for the last three months and who had no current vaso-occlusive crises were evaluated. All the patients were grouped according to the frequency of the crises for the previous year preceding the data collection. Group 1: 1 to 3 crises, Group 2: 4 to 5 and Group 3: 6 or more crises annually. RESULTS: In accordance with the results obtained during the evaluation of the cases diagnosed with sickle-cell anemia, MPV value was found to be significantly higher in patients with cerebrovascular events. Also MPV values increased with increasing incidence of the crises (r=0.297) (p=0.001). CONCLUSION: One of the contributing factors for this clinical heterogeneity may be related to the MPV values in patients with sickle cell anemia. The higher MPV values may be an early predictor of future cerebrovascular events in patients with sickle cell anemia and may require close follow-up and additional measures.

Spectrum of α-thalassemia mutations including first observation of - -(FIL) deletion in Hatay Province, Turkey.

Alpha thalassemia (α-thal) is one of the most common genetic disorders in the world. It is characterized by the absence or reduced expression of α-globin genes. The frequency of α-thal mutations in the province of Hatay in South Turkey is unknown. Therefore, in the present study, we aimed to investigate the spectrum of α-thal mutations in this province. Three hundred and nine patients were tested for α-thal mutations by using reverse dot blot hybridization technique and nine different mutations were detected in 97 of them. Among the 9 different mutations found, the most frequent mutations were the -α(3.7) (43.81%), -α2(-5nt) (6.70%), - -(MED) (5.67%) and α2(Poly A2) (2.57%). In the present study, - -(FIL) mutation was detected in a patient for the first time in Turkey. Our results indicated that α-thal mutations are highly heterogeneous and -α(3.7) is the most prevalent mutation in Hatay province of South Turkey. In addition, - -(FIL) mutation was detected in a patient for the first time in Turkey. This new finding may contribute to the establishment of a national mutation database and genetic counseling.

Neuroimaging Findings in Pediatric Patients with Thalassemia Major.

BACKGROUND: Cranial magnetic resonance imaging (MRI) studies about iron accumulation in children with thalassemia major are quite limited. AIM: This study aimed to detect neurological findings with cranial MRIs in the pediatric patients with thalassemia major who did not develop any neurological complications. MATERIALS AND METHODS: Pediatric patients with thalassemia major who followed in the Pediatric Hematology Unit between 1 July 2017 and 1 January 2019 were included in the study. The patients underwent cranial MRI scans. RESULTS: A total of 30 patients were included. The median age was 15 (range from 4-18) years old. We found that 7 patients had a splenectomy and 19 of the remaining 23 patients had splenomegaly. In addition, 13 of the patients had hepatomegaly, 10 had skeletal deformities, and 17 had growth retardation. The mean ferritin level was 3772.3 ± 2524.8. We detected various pathologies on cranial MRI images of 10 (33.3%) patients. In 3 of these patients, millimeter-sized ischemia-compatible lesions were found in the cerebral white matter, which did not fit any arterial area, and 5 patients had hyperintense lesions in the basal ganglia. CONCLUSION: Our study is valuable since 1/3 of our pediatric patients with thalassemia major were detected with intracranial pathology.

Hemoglobin H Disease in Turkey: Experience from Eight Centers.

The purpose of this study was to research the problem of hemoglobin H (HbH) disease, to reveal the distribution patterns among different health centers, and to emphasize the importance of this disease for Turkey. A total of 273 patients were included from 8 hemoglobinopathy centers. The Antakya Hemoglobinopathy Center reported 232 patients and the remaining 7 centers reported 41 patients. PubMed was also searched for published articles related to Turkish patients with HbH disease, and we found 16 articles involving a total of 198 HbH patients. Most of the patients were reported from Antakya; thus, special attention should be paid to this region. This is a preliminary study to investigate the extent of the problem of HbH disease and it emphasizes the need for hematology associations or the Ministry of Health to record all cases of HbH disease in Turkey.

Anxiety, depression and quality of life in patients with beta thalassemia major and their caregivers.

Mental health and health related quality of life is commonly affected in patients with chronic problems and their caregivers. In the present study, it was aimed to assess depression and anxiety in patients with beta thalassemia major (BTM) and in their caregivers; and to evaluate effects of these disorders on quality of life. The study was carried out in a district Hereditary Hemoglobinopathy Center and included 88 patients with BTM and 63 of their caregivers. All subjects were assessed using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Short Form-36 (SF-36) by a trained psychiatry resident via face-to-face interview. The BDI scores were 17 or above in 20.5% of the patients with BTM and 28.6% of their caregivers (P = 0.248). Of the patients with BTM, there were mild anxiety symptoms in 19.3%, while moderate and severe anxiety symptoms in 14.8% and 4.5%, respectively. Anxiety levels were similar between the patients with BTM and their caregivers (P = 0.878). It was found that BDI and BAI scores were negatively correlated to scores of physical health and mental health components of SF-36 in patients with BTM and their caregivers. In linear regression analysis, it was seen that depression affected physical and mental health of the patients with BTM and their caregivers regardless from anxiety. BTM leads an increase in the frequency of depression and anxiety in both patients and their caregivers, and affects negatively physical and mental components of quality of life.

Lipoprotein subfraction profile and HDL-associated enzymes in sickle cell disease patients.

Although hypocholesterolemia is a reported finding in sickle cell disease (SCD), low-density lipoprotein (LDL)/high-density lipoprotein (HDL) subfractions and HDL-associated enzymes have not been determined in SCD patients. Blood was collected from 38 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients who had not received blood transfusions in the last 3 months. Serum lipids were measured by automated analyzer while LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Serum levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were significantly decreased, while TG levels were significantly increased in SCD patients compared to controls. A significant decrease in intermediate-density lipoprotein (IDL)-C, IDL-B, IDL-A and LDL-1 fractions were seen in SCD patients, while no significant difference was observed in small dense LDL particles. A significant decrease was seen in HDL-large, HDL-intermediate and HDL-small fractions in SCD patients versus controls. Levels of LCAT and ApoA-1 protein measured in SCD patients were significantly lower while no significant difference was observed in CETP and ApoB protein levels compared to controls. The reduction observed in LDL- and HDL-C in SCD patients was reflected as significantly decreased IDL, LDL-1 and HDL-subfractions. Decreased HDL subfractions may possibly lead to the reduced ApoA-1 and LCAT protein levels observed in SCD patients.

Nocturnal enuresis in sickle cell disease and thalassemia major: associated factors in a clinical sample.

In this study, we aimed to investigate the prevalence and associated factors of nocturnal enuresis in sickle cell disease (SCD) and thalassemia major (TM) patients in a single center from Turkey. One hundred and six patients, 51 (48.1 %) with TM and 55 (51.9 %) with SCD, and 80 age-matched healthy controls were included in the study. Semi-structured interviews were conducted with the caregivers of pediatric and adult patients. The interview included questions on nocturnal enuresis and psychosocial variables. Patients' hospital files were reviewed to search for disease-related factors. Twenty-eight of the patients (26.4 %) and three (3.7 %) of the controls had nocturnal enuresis. Younger age, TM diagnosis, family history of nocturnal enuresis and family problems were found to be more frequent in patients with nocturnal enuresis. Among the patients with SCD, frequencies of hospitalization and painful crises were found to be higher in those with enuresis. According to the binary logistic regression analysis, diagnosis of TM (p = 0.031, OR = 0.262) and younger age (p = 0.005, OR = 0.869) were found to be independent risk factors for nocturnal enuresis in the patient group. Nocturnal enuresis is a common problem in children and young adults with TM and SCD. Associated factors in both conditions will be clarified with future studies.