Serum Soluble Transferrin Receptor in Heterozygous β-Thalassaemia: Application in the Diagnosis of Iron Deficiency and as Hematologic Marker of Erythroid Activity According to Thalassaemic Genotypes (β0 vs β+).
Authors: Calvo-Villas Jose Manuel , Zapata María Francisca , Alvarez Ivan , de la Iglesia Silvia , Cuesta Jorge , Carreter Elena , Sicilia Francisco 
Published: October 2019

Although an increased level of serum soluble transferrin receptor (sTfR) have been found in both heterozygous β-thalassaemia patients with iron deficiency and in those with more severe genotype (β0), it is not a useful marker of iron deficiency status associated to β-thalassaemia. The aim of this study was to analyse the use of two biochemical parameters (sTfR and sTfR/log of ferritin ratio) to determine the iron status and to evaluate the degree of erythropoietic activity in a group of 221 β-thalassaemic heterozigotes patients (155 β0 and 66 β+). Serum ferritin and transferrin saturation index were measured in order to establish the iron status. Of the whole group, 51 patients were iron defficient (βthal-ID) while the remaining 170 were iron sufficient (βthal-IS). Based on the combination of β-thalassaemia genotype and iron status, patients were classified into four subgroups:

β0thalassaemia and iron-sufficient (β0thal-IS) (n=124); β0thalassaemia and iron-deficient (β0thal-ID) (n=31); β+thalassaemia and iron-sufficient (β+thal-IS) (n=46); β+thalassaemia and iron-deficient (β+thal-ID) (n=20).

258 healthy and 56 iron-deficient individuals were used as controls. All the haematological parameters were measured by using analyzer Coulter® GEN-S™. Haemoglobins A2 (Hb A2) and F (HbF) were analysed by high performance liquid chromatography and molecular analysis was performed by real-time PCR and direct sequencing techniques. Chemical, inmunoturbidimetrical and nephelometric methods were used to measure iron status as well as sTfR. Comparison of haemalogical and biochemical parameters between subgroups was performed by using the t-student test and correlation analysis was calculated by using least-squares regression model. Mean sTfR level obtained was 2.63 ± 0.8 mg/dL and 2.57 ± 1.1 mg/dL in βthal-ID and βthal-IS patients respectively (p=0.783). Soluble transferrin receptor showed a positive correlation with HbA2, HbF and reticulocyte count values in βthal-IS patients (r=0.208 [p<0.05], r=0.440 [p<0.0001] and r=0.393 [p<0.00001] respectively) while it did not reach a significant correlation in βthal-ID patients. Mean sTfR/log sFt ratio was 2.75 ± 1.6 and 1.34 ± 0.5 in βthal-ID and βthal-IS patients (p<0.001). Interestingly, sTfR level was significantly higher in β0thal-IS patients when compared with β+thal-IS patients (2.76 ± 0.9 vs 1.42 ± 0.4) (p<0.001) as a result of an increased globin chains imbalance related to the β0 genotype. In the other hand, in the comparison between β0thal-ID and β+thal-ID subgroups neither sTfr level (2.71 ± 0.7 vs 2.40 ± 1.1) (p=0.417) nor sTfR/log sFt ratio (2.93 ± 1.7 vs 2.24 ± 1.3) (p=0.371) showed significant difference. In summary, sTfR/log sFt ratio is a valid parameter for diagnosis of iron deficiency associated to heterozygous β-thalassaemia. Unlike the findings observed in β-thalassaemic heterozigotes with normal iron status, sTfR level is not useful to evaluate the genotype severity in those with iron deficiency. Consequently, iron status should be determined before using sTfR as a parameter to provide a reliable estimation of the ineffective erythropoiesis related to the severity of β-thalassaemia genotypes.