The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?

INTRODUCTION: Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. METHODS: This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. RESULTS: One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. CONCLUSIONS: The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.

Presentation of Compound Heterozygous Hemoglobin Constant Spring and Hemoglobin Pakse in Neonates.

BACKGROUND: Mutations causing α thalassemia are divided into deletion and nondeletion groups. In the nondeletion group, hemoglobin constant spring (Hb CS) and hemoglobin Pakse (Hb Pakse) are both caused by a termination codon mutation leading to elongation of the α2 globin gene. In the case of Hb CS, the mutation is TAA→CAA, whereas the mutation causing Hb Pakse is TAA→TAT. Clinical hematologic phenotypes are not significantly different. It is important to identify compound heterozygotes for purposes of genetic counseling. METHODS: We report 5 neonates with compound heterozygous Hb CS/Hb Pakse mutations with respect to clinical courses, hematologic profiles, and management. RESULTS: Among 5 cases (3 male babies and 2 female babies) with mean birth weight 2982 g (range, 2660 to 3440 g), 3 were diagnosed as compound heterozygous Hb CS/Hb Pakse, 1 as homozygous Hb E with compound heterozygous Hb CS/Hb Pakse, and 1 as heterozygous Hb E with compound heterozygous Hb CS/Hb Pakse. Clinical manifestations included fetal anemia (1 case), neonatal hyperbilirubinemia (5), neonatal anemia (2), hepatosplenomegaly (1), and cholestatic jaundice (1). Three cases required a single phototherapy; 2 cases needed double phototherapy for treatment of severe hyperbilirubinemia. During the first few months of life, all cases had mild anemia, slightly low mean corpuscular volume, wide red cell distribution width, and low red cell counts. At 1 to 3 years of age, all patients still had mild microcytic hypochromic anemia with Hb levels around 10 g/dL, increased reticulocyte count, and wide red cell distribution width. CONCLUSIONS: Misdiagnosis of Hb Pakse could occur via Hb typing using Hb electrophoresis, because the band comigrates with that of Hb CS. DNA study is the definitive method for diagnosis.

Effect of Yisui Shengxue Granule () on the oxidative damage of erythrocytes from patients with hemoglobin H disease.

OBJECTIVE: To investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease. METHODS: Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined. RESULTS: In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment. CONCLUSIONS: YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of ß-globin chains.

Sensitivity of different thalassaemia genotypes to food mutagens in the Comet assay.

Thalassaemia is a heterogeneous group of inherited anaemias, characterised by a reduction or total absence of one or more of the globin chains of haemoglobin. Individuals with thalassaemia major require regular blood transfusions in order to maintain their haemoglobin concentration at an appropriate level. An essential treatment in parallel with transfusions is iron chelation therapy to remove excess iron deposited in tissues from the transfused blood. The high iron levels in these patients make free oxygen radicals accessible, for example, through Fenton-type chemistry, and generate superoxide and hydroxyl radicals. Increased oxygen radical capacity is known to be associated with cancer and ageing. In a previous study, it has been shown that peripheral blood lymphocytes isolated from a sickle/beta thal double heterozygote-sickle phenotype thalassaemia patient, who was not undergoing chelation therapy, showed increased sensitivity to the effects of oxygen radicals and iron salts by comparison with lymphocytes from normal controls. Furthermore, in a later study, this patient also showed increased sensitivity to the dietary food mutagen 3-amino-1-methyl-5H-pyridol(4,3-b)indole (Trp-P-2) when compared to the control. The present study, therefore, investigated whether the above observation could be duplicated using different food mutagens in different thalassaemia genotypes. The effect of the food mutagens 2-amino-2-methylimidazolo(4,5-f)quinolone (IQ) and 2-amino-1-methyl-6-phenylimidazol(4,5-b)pyridine (PhIP) on lymphocytes of three different thalassaemia patients, a beta-thalassaemia major, a beta-thalassaemia/Hb E, and an alpha-thalassaemia trait with a 3.7-kb deletion, who were not undergoing chelation therapy were investigated using the Comet assay. All three thalassaemia genotypes showed increased sensitivity to both IQ and PhIP in comparison to the control, although with PhIP at the highest two concentrations (50 and 75 microM) the differences monitored with the alpha-thalassaemia trait were found not to be statistically significant (P > 0.05).