Peripheral Blood Erythrocyte Parameters in Β-Thalassemia Minor with Coexistent Iron Deficiency: Comparisons between Iron-Deficient and -Sufficient Carriers

Round 1

Reviewer 1 Report

The authors of this manuscript report the change in haematological values in healthy subjects with beta thalassemia in the presence of iron deficiency (ID).

The manuscript is well written and comprehensive. It would have been interesting to correlate the mutations of the beta globin gene in BTM subjects and the variation of HbA2 in BTM-ID + and ID- subjects. These data could further make the manuscript more interesting to readers

Author Response

Thank you for your helpful comments.

To confirm the carrier state, genetic analysis of β-thalassemia are not performed in pediatric cases in our country and our clinic. Thus the causative β-thalassemia mutations in our study population are not known. Their diagnosis is based on CBC and HPLC results PLUS parental study (presence of a similar situation in at least one parent would indicate thalassemia). Hence, the diagnosis is definitive but the causative mutations are not known.

As you suggested, different β-thalassemia mutations have different effects on Hb A2 levels and, more importantly, on CBC parameters. Hb A2 levels in ID+ and ID- carriers are presented in Table 2 but, unfortunately, correlation  between Hb A2 levels and mutations is not available. It is our hope that further studies with advanced genetical laboratory facilities will facilitate clarification of such important points.

We added a paragraph in the revised manuscript to adress this issue. 

Since thalassemia mutations leading to erythrocyte changes are population specific, considering this situation in future AI tools in different populations might be helpful.

Reviewer 2 Report

Thanks for carrying out the work. It would be better if you could have derived a mathematical model for predicting change in the RBC indices in the presence of iron deficiency. Since there is an overlap between the two groups, I would suggest you to prioritise the parameters one should look at, if there is suspected iron deficiency in a beta thalassemia minor child. The work would be much more valuable if the readers understood the way to look at the parameters in presence of iron deficiency.

Author Response

Thank you for your helpful comments.

This is a preliminary study. With this brief report, we wish to bring to light the importance of this issue. We believe that future studies by other interested groups in large patient populations (e.g., nation-wide) and with defined underlying β-thalassemia mutations will facilitate data collection which is required for developing correct mathematical algorithms utilized by artificial intelligence programs.

The results of our study demonstrated that in B-TT coexistent with ID, carriers have hypochromic microcytic anemia with elevated RBC and RDW. This clear message was added to the revised manuscript.