Causes of Hospitalizations in Pediatric Patients with Thalassemia under the National Health Coverage Scheme in Thailand

Round 1

Reviewer 1 Report

This study aims to assess the admission rate, co-diagnoses, and hospital cost for admission in pediatric patients on all type of thalassemia disease under the National Health Coverage Scheme of Thailand form 2015 - 2019. The diagnosis is based on ICD.10 and the cost of hospital admission in Thai baht was collected annually. The study included 41,237 patients with thalassemia disease with 5 age group. The study revealed the highest admission rate within the 11-<16 years age group and the lowers in infants. Most hospitalized patients had beta-thalassemia, hemachromatosis, and infections as co-diagnoses. In addition, this study found a significant presence of cardiovascular complications and diabetes mellitus. The study also found that the diagnosis of hemochromatosis doubled, which indicates improved access to medication while admission for iron overload-related complications (CVD and diabetes mellitus declined). The study concluded that infections was the domination complications in younger patients while cardiac issues and diabetes mellitus showed a significant risk in older children.

This study discusses the issue of hospital admission among pediatric patients with thalassemia in a clear and concise manner with reproducible methodology. The authors already mentioned the study's limitations and strengths.

No revision is required. 

Author Response

Author’s reply:

We thank the reviewer for their valuable and positive comments.

Reviewer 2 Report

The authors present a retrospective study to assess the admission rate, co-diagnoses, and cost of hospital admission in pediatric patients with thalassemia under the National Health Coverage (NHC) scheme in Thailand. The topic is relevant since it underscores the burden thalassemia represents nationwide in Thailand both to the hospital system as well as financially. I suggest a few clarifications that can improve the overall quality of the manuscript:

1- page 1, line 42: the authors mention TDT and NTDT definitions in their introduction, but patients were not stratified as such. Is that possible? That would highlight whether TDT is responsible for most admissions or not. I understand using ICD codes may prevent that distinction.

2- page 2, lines 74-76: the authors should make the rates very explicitly clear, please specify what the numerators and denominators are. In understand "Number of patient admissions/100 admissions" should be number of thalassemia patient admissions/100 NHC admissions in the general population.  Based on the results, I understand "Number of patient admissions/100,000 population" - is per 100,000 people in the general population (not per 100,000 thalassemia patients). 

3- page 6, line 187: It would be desirable to convert baht to US dollar based on the average exchange rate of the year considered, not 2023 rates.

4- is it possible to retrieve what percentage of admissions require intensive care unit? That adds a lot to cost and could be an interesting angle to explore.

5- the authors should expand the limitations section by commenting on how their data prevent more granularity around the specific thalassemia diagnosis. The most prominent omission is HbE-beta versus non-HbE thalassemia, given the high prevalence of HbE in Thailand. One wonders if unclassified thalassemia may include HbE-beta patients.

6-The authors should include comments on the overall increase in admissions, and the fact that iron overload increased along with it. Does it reflect better care for infants and better survival? Does it reflect access to transfusion but not chelation? 

7- It would be important for authors to include some data on the landscape of iron chelation in Thailand, at least to discuss whether use of oral chelation is a possible effect to decrease mesenteric lymphadenitis as reported by others. 

Minor non-English expressions in the text.

Author Response

The authors present a retrospective study to assess the admission rate, co-diagnoses, and cost of hospital admission in pediatric patients with thalassemia under the National Health Coverage (NHC) scheme in Thailand. The topic is relevant since it underscores the burden thalassemia represents nationwide in Thailand both to the hospital system as well as financially. I suggest a few clarifications that can improve the overall quality of the manuscript:

Author’s reply:

We thank the reviewer for the valuable comments and suggestions.

1- page 1, line 42: the authors mention TDT and NTDT definitions in their introduction, but patients were not stratified as such. Is that possible? That would highlight whether TDT is responsible for most admissions or not. I understand using ICD codes may prevent that distinction.

Author’s reply:

We agree with the reviewer regarding the usefulness of classifying severity into TDT and NTDT. However, such classification is not feasible due to the limitations of information extracted using ICD codes.

We have added the limitations in the Discussion part.

Revision:

Page 8, Lines 243-247

“Of note, the information obtained through ICD codes presented limitations in diagnosing thalassemia and classifying its severity. The grouping of beta-thalassemia major and beta-thalassemia/Hb E disease under the same ICD10 codes rendered differentiation impractical. The classification into TDT and NTDT was not possible. Additionally, a notable percentage consisted of other thalassemias or unspecified thalassemia.”

2- page 2, lines 74-76: the authors should make the rates very explicitly clear, please specify what the numerators and denominators are. In understand "Number of patient admissions/100 admissions" should be number of thalassemia patient admissions/100 NHC admissions in the general population.  Based on the results, I understand "Number of patient admissions/100,000 population" - is per 100,000 people in the general population (not per 100,000 thalassemia patients). 

Author’s reply:

We appreciate the reviewer's valuable suggestion. The Materials and Methods section has been revised to enhance clarity regarding the rates.

Original:

“Admission rates were calculated based on NHC admissions (number of patient admissions/100 admissions) and the total population in the respective age group (number of patient admission/100,000 population).”

Revision:

Page 2, Lines 86-88

“Admission rates were calculated based on NHC admissions (number of thalassemia patient admissions/100 NHC admissions) and the total NHC population in the respective age group (number of thalassemia patient admission/100,000 NHC population).”

3- page 6, line 187: It would be desirable to convert baht to US dollar based on the average exchange rate of the year considered, not 2023 rates.

Author’s reply:

We thank the reviewer for the insightful suggestion. The currency conversion rate has been adjusted based on the average exchange rate for the years 2015-2019.

Data from ref. 19: Bank of Thailand Daily foreign exchange rates. Available online: https://www.bot.or.th/en/statistics/exchange-rate.html

Original:

“The financial implications of thalassemia-related hospital admissions were substantial, with costs ranging from 281.8 to 375.1 million baht or 7.9 to 10.6 million US dollar (at the rate of 35.38 baht for 1 US dollar, 2023 exchange rate [13]) per year.”

Revision:

Page 7, Lines 218-220

“The financial implications of thalassemia-related hospital admissions were substantial, with costs ranging from 281.8 to 375.1 million baht or 8.19 to 12.01 million US dollar per year, based on the average yearly currency exchange rate of 31.21-35.46 baht for 1 US dollar, 2015-2019 exchange rate [19].”

4- is it possible to retrieve what percentage of admissions require intensive care unit? That adds a lot to cost and could be an interesting angle to explore.

Author’s reply:

It is not possible to retrieve the details of intensive care unit submission. We agree with the reviewer that the information would have been useful.

5- the authors should expand the limitations section by commenting on how their data prevent more granularity around the specific thalassemia diagnosis. The most prominent omission is HbE-beta versus non-HbE thalassemia, given the high prevalence of HbE in Thailand. One wonders if unclassified thalassemia may include HbE-beta patients.

Author’s reply:

We thank the reviewer for the valuable suggestion. We have added the limitations in the Discussion part.

Revision:

Page 8, Lines 243-247

“Of note, the information obtained through ICD codes presented limitations in diagnosing thalassemia and classifying its severity. The grouping of beta-thalassemia major and beta-thalassemia/Hb E disease under the same ICD10 codes rendered differentiation impractical. The classification into TDT and NTDT was not possible. Additionally, a notable percentage consisted of other thalassemias or unspecified thalassemia.”

6-The authors should include comments on the overall increase in admissions, and the fact that iron overload increased along with it. Does it reflect better care for infants and better survival? Does it reflect access to transfusion but not chelation? 

Author’s reply:

We thank the reviewer for the valuable suggestion. The overall increase in admissions and diagnosis of iron overload reflects the better awareness of iron overload and its related complications which leads to favorable outcomes. We have added this information in the Discussion part.

Original:

“Over the study period, the diagnosis of hemochromatosis doubled, indicating improved access to medications. Concurrently, admissions for iron overload-related complications, such as cardiac issues and diabetes mellitus, declined.”

Revision:

Page 7, Lines 228-232:

“Over the study period, the diagnosis of hemochromatosis doubled, indicating improved access to medications. Concurrently, admissions for iron overload-related complications, such as cardiac issues and diabetes mellitus, declined. This trend indicates improved awareness of iron overload and its associated complications, resulting in more favorable outcomes.”

7- It would be important for authors to include some data on the landscape of iron chelation in Thailand, at least to discuss whether use of oral chelation is a possible effect to decrease mesenteric lymphadenitis as reported by others. 

Author’s reply:

We thank the reviewer for the insightful suggestion. We have added the information on iron chelation in Thailand in the Discussion part.

Revision:

Page 7, Lines 207-212

“In Thailand, from 2015 to 2017, the first-line iron chelators utilized were desferrioxamine and deferiprone. Oral deferiprone was administered to children aged six years and above. From 2018, under the NHC scheme, deferasirox became the first-line iron chelator for children aged 2 to 6 years old. The prevalent use of oral iron chelators might have reduced the incidence of mesenteric lymphadenitis compared to these earlier studies.”

Comments on the Quality of English Language

Minor non-English expressions in the text.

Author’s reply:

We thank the reviewer for the suggestion. We rechecked and removed the non-English expressions in the text.

Reviewer 3 Report

I think this a very important article. Main data concern on the cross-sectional big data obtained from the National Health Coverage Scheme in Thailand. The authors evaluated prevalence of Thalassemia in different generation between infant to people under 18 year old. The authors show admission rates and complications. Findings in this manuscript are very worthy for future progress in Thalassemia treatment.

My comments and suggestions:

1.     For showing the effectiveness of iron chelation therapy, it is better to compare with other medications such as luspatercept mentioned in “2021 Thalassemia International Federation Guidelines” in addition to already mentioned therapy in the manuscript.

2.     Most important findings in this manuscript seems to be in infant data. Rate/100 admissions was 0.01 in infant period (Table 2). Readers may focus on the reason why low admission in infant and ages under 6. It is better to explain more about this point. It may show some unmet needs in Thalassemia treatment.

3.     The authors should give comments on situation of reproductive medicine. Although it may the issue out of “pediatrics”, most severe case such as hydrops fetalis or death birth etc. might influence data in infant period.

4.     If there is Thalassemia registry, the author can compare data between registry and NHC data.

I think acceptable for publication after minor revisions.

Author Response

I think this a very important article. Main data concern on the cross-sectional big data obtained from the National Health Coverage Scheme in Thailand. The authors evaluated prevalence of Thalassemia in different generation between infant to people under 18 year old. The authors show admission rates and complications. Findings in this manuscript are very worthy for future progress in Thalassemia treatment.

Author’s reply:

We thank the reviewer for their valuable and positive comments.

My comments and suggestions:

1. For showing the effectiveness of iron chelation therapy, it is better to compare with other medications such as luspatercept mentioned in “2021 Thalassemia International Federation Guidelines” in addition to already mentioned therapy in the manuscript.

Author’s reply:

We thank the reviewer for this valuable suggestion. As luspatercept has not been approved in children under 18 years of age, we have not included the treatment in the manuscript.

2. Most important findings in this manuscript seems to be in infant data. Rate/100 admissions was 0.01 in infant period (Table 2). Readers may focus on the reason why low admission in infant and ages under 6. It is better to explain more about this point. It may show some unmet needs in Thalassemia treatment.
3. The authors should give comments on situation of reproductive medicine. Although it may the issue out of “pediatrics”, most severe case such as hydrops fetalis or death birth etc. might influence data in infant period.

Author’s reply to comments 2 and 3:

We thank the reviewer for the useful suggestions about the low admission rates in infants and prenatal screening of thalassemia. We have included these important points to the Discussion part.

Revision:

Page 7, Lines 233-242

“As this study encompassed all diagnoses of thalassemia, spanning from NTDT to TDT, the low admission rate in infants and young children could indicate patients with milder forms of the disease, such as Hb H disease, which tends to be diagnosed at an older age. This observation may also highlight an existing unmet need. While a successful universal screening program for couples at risk of fetal severe thalassemia diseases, including beta-thalassemia major, beta-thalassemia/Hb E disease, and Hb Bart’s hydrops fetalis, has been implemented in Thailand [18], neonatal screening is not currently available. The establishment of universal neonatal screening for thalassemia in Thailand could play a significant role in the early diagnosis of severe thalassemia not screened prenatally, as well as milder forms of thalassemia. and improved management, leading to better outcomes.”

4. If there is Thalassemia registry, the author can compare data between registry and NHC data.

Author’s reply:

Thank you for this important comment. Unfortunately, due to the absence of a national thalassemia registry in Thailand, we are unable to make comparisons.

I think acceptable for publication after minor revisions.

Author’s reply:

We thank the reviewer for the valuable and positive suggestions.

Reviewer 4 Report

Comments for author File: Comments.pdf

Author Response

Please find the author’s reply in the attached pdf.

Author Response File: Author Response.pdf

Reviewer 5 Report

THIS IS A CROSS-CROSS STUDY EVALUATING CAUSES OF ADMISSION IN THALASSEMIA, IN ADDITION TO A COST ANALYSIS. BETA THALASSEMIA WERE GROUPED. NO TRANSFUSION COSTS WERE DEFINED.

I SUGGEST SEPARATING BY TYPE OF THALASSEMIA (INTERMEDIA, MAJOR, MINOR) FOR A MORE ROBUST ANALYSIS AND RESULTS. IN THE LITERATURE THERE ARE ARTICLES ON COSTS IN HEMOGLOBINOPATHIES THAT SHOULD BE INCLUDED. DEFINE OTHER THALASSEMIAS. WHICH MUTATION IS RELATED TO ALPHATHALASSEMIA. DOES DIAGNOSIS IN NEONATAL SCREENING HAVE AN IMPACT BEYOND CHELATION? IS THERE ASSOCIATION WITH SICKLE CELL ANEMIA IN THE REPORTED CASES? HYDROXYUREA USE? WHAT INCIDENCE OF THALASSEMIA IN THE COUNTRY? USE OF luspatercept?

Author Response

This is a cross-cross study evaluating causes of admission in thalassemia, in addition to a cost analysis. Beta thalassemia were grouped. No transfusion costs were defined.

I suggest separating by type of thalassemia (intermedia, major, minor) for a more robust analysis and results.

Author’s reply:

We thank the reviewer for the valuable comments and suggestions. We agree with the reviewer that classifying the severity into intermedia, major and minor thalassemia will be useful. However, this is not possible due to the limitation of information retrieved by using ICD codes. We have addressed the limitations in the Discussion part.

Revision:

Page 8, Lines 243-247

“Of note, the information obtained through ICD codes presented limitations in diagnosing thalassemia and classifying its severity. The grouping of beta-thalassemia major and beta-thalassemia/Hb E disease under the same ICD10 codes rendered differentiation impractical. The classification into TDT and NTDT was not possible. Additionally, a notable percentage consisted of other thalassemias or unspecified thalassemia.”

In the literature there are articles on costs in hemoglobinopathies that should be included.

Author’s reply:

We have included articles on costs of treatment in patients with hemoglobinopathies.

Original:

“The cost of treatment in thalassemia is high and contributes to a significant healthcare burden in endemic regions [4-7].”

Revisions:

Page 2, Lines 50-54

“The cost of treatment in thalassemia is high and contributes to a significant healthcare burden in endemic regions [5-10]. In Western countries, the estimated treatment expenses are generally higher [11, 12]. Among patients with TDT, the primary factors contributing to these costs are blood transfusions and iron chelation.”

Added references:

Reed-Embleton, H.; Arambepola, S.; Dixon, S.; Maldonado, B.N.; Premawardhena, A.; Arambepola, M.; Khan, J.A.M.; Allen, S. A cost-of-illness analysis of beta-Thalassaemia major in children in Sri Lanka - experience from a tertiary level teaching hospital. BMC Pediatr 2020, 20, 257, doi:10.1186/s12887-020-02160-3.

9. Uchil, A.; Muranjan, M.; Gogtay, N.J. Economic burden of beta-thalassaemia major receiving hypertransfusion therapy at a public hospital in Mumbai. Natl Med J India 2023, 36, 11-16, doi:10.25259/NMJI_580_20.
10. Esmaeilzadeh, F.; Ahmadi, B.; Vahedi, S.; Barzegari, S.; Rajabi, A. Major Thalassemia, Screening or Treatment: An Economic Evaluation Study in Iran. Int J Health Policy Manag 2022, 11, 1112-1119, doi:10.34172/ijhpm.2021.04.
11. Eleftheriou, A.; Antoniou, E.; Darba, J.; Ascanio, M.; Angastiniotis, M.; Farmakis, D. Estimating the Cost of Thalassemia Care across the World: A Thalassemia International Federation Model. Hemoglobin 2022, 46, 308-311, doi:10.1080/03630269.2023.2167657.
12. Udeze, C.; Evans, K.A.; Yang, Y.; Lillehaugen, T.; Manjelievskaia, J.; Mujumdar, U.; Li, N.; Andemariam, B. Economic and clinical burden of managing transfusion-dependent beta-thalassemia in the United States. J Med Econ 2023, 26, 924-932, doi:10.1080/13696998.2023.2235928.

Define other thalassemias. Which mutation is related to alpha-thalassemia.

Author’s reply:

We were not able to define “other thalassemias”, and the mutations causing thalassemia due to the limitation of information retrieved by using ICD codes. We agree with the reviewer that the information would have added a better understanding. We have addressed the limitations in the Discussion part.

Does diagnosis in neonatal screening have an impact beyond chelation? Is there association with sickle cell anemia in the reported cases? Hydroxyurea use? What incidence of thalassemia in the country? Use of luspatercept?

Author’s reply:

Neonatal screening program has not been implemented in Thailand. We agree with the reviewer that early diagnosis by neonatal screening should contribute to early treatment and has a significant impact on treatment outcome.

The main types of thalassemia diseases in Thai population are homozygous beta-thalassemia, beta-thalassemia/Hb E disease and Hb H disease. Sickle cell anemia is rare in Thai population.

The frequency of alpha-thalassemia carriers and beta-thalassemia carriers in the population is approximately 20-30% and 3-9%, respectively. Hb E, a common Hb variant in the region, has a prevalence ranging from 10% to 53%. Additionally, the prevalence of Hb Constant Spring, a common non-deletional alpha-thalassemia, is estimated to be between 1% and 8%.

We added this information in the Introduction part.

Page 1, Lines 41-45

“The frequency of alpha-thalassemia carriers and beta-thalassemia carriers in the population is approximately 20-30% and 3-9%, respectively. Hb E, a common Hb variant in the region, has a prevalence ranging from 10% to 53%. Additionally, the prevalence of Hb Constant Spring, a prevalent non-deletional alpha-thalassemia, is estimated to be between 1% and 8% [2].”

The information on hydroxyurea use was not available. Luspartercept in children under 18 years of age was not available during the study period.

Round 2

Reviewer 5 Report

The authors report that thalassemia is the most common hereditary anemia in the world, and correction is necessary. Sickle cell disease has a prevalence of 7% and is the most common. There are other classifications of thalassemia not focused on dependence on hemotherapy support. Gene therapy is already being used as a curative treatment, it is appropriate to include an article. It was not clear whether there is a need for chelation at the hospital level, especially when studying children. In the results, there is no way to separate whether the same patient had several hospitalizations, which could determine an analysis bias. These intestinal infections are all related to thalassemia, the description of the article is not clear. In the discussion, the articles cited only investigated children too, it was not clear. Treatment of thalassemia with transfusion is normally outpatient. Perhaps the inclusion of neonatal screening as a cost reduction strategy should be addressed in the discussion and conclusion, including cost reduction.

Author Response

Thank you very much for providing us the opportunity to revise the manuscript No. thalassrep-2797181 (Revision 2) entitled "Causes of Hospitalizations in Pediatric Patients with Thalassemia under the National Health Coverage Scheme in Thailand". We also thank the reviewers for their valuable and insightful comments and suggestions. Below are our responses to the reviewer’s comments. The changes are highlighted in yellow in the manuscript file.

Reviewers' comments:

The authors report that thalassemia is the most common hereditary anemia in the world, and correction is necessary. Sickle cell disease has a prevalence of 7% and is the most common. There are other classifications of thalassemia not focused on dependence on hemotherapy support. Gene therapy is already being used as a curative treatment, it is appropriate to include an article.

Author’s reply:

We thank the reviewer for the valuable comments and suggestions. We revised the manuscript as per the reviewer’s suggestions.

Page 1, Lines 37-38

Original:

“Thalassemia is the most common inherited hemolytic anemia globally and is highly prevalent in Southeast Asian countries including Thailand.”

Revision:

"Thalassemia and hemoglobinopathies are the most common inherited hemolytic anemias globally and are highly prevalent in Southeast Asian countries, including Thailand."

Page 2, Lines 46-48

Original:

“Thalassemia diseases are classified by the need for transfusion into transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) [3].”

Revision:

“Thalassemia diseases can be classified by the need for transfusion into transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) [3].”

Page 2, Lines 50-51

Revision:

“Gene therapy has emerged as a curative treatment for thalassemia [4-6].”

Added references

4. Thompson, A.A.; Walters, M.C.; Kwiatkowski, J.; Rasko, J.E.J.; Ribeil, J.A.; Hongeng, S.; Magrin, E.; Schiller, G.J.; Payen, E.; Semeraro, M.; et al. Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med 2018, 378, 1479-1493, doi:10.1056/NEJMoa1705342.
5. Frangoul, H.; Altshuler, D.; Cappellini, M.D.; Chen, Y.S.; Domm, J.; Eustace, B.K.; Foell, J.; de la Fuente, J.; Grupp, S.; Handgretinger, R.; et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and beta-Thalassemia. N Engl J Med 2021, 384, 252-260, doi:10.1056/NEJMoa2031054.
6. Locatelli, F.; Thompson, A.A.; Kwiatkowski, J.L.; Porter, J.B.; Thrasher, A.J.; Hongeng, S.; Sauer, M.G.; Thuret, I.; Lal, A.; Algeri, M.; et al. Betibeglogene Autotemcel Gene Therapy for Non-beta(0)/beta(0) Genotype beta-Thalassemia. N Engl J Med 2022, 386, 415-427, doi:10.1056/NEJMoa2113206.

It was not clear whether there is a need for chelation at the hospital level, especially when studying children.

Author’s reply:

We thank the reviewer for the insightful comments. During the study period, from 2015 to 2017, the first-line iron chelators utilized in Thailand were desferrioxamine and deferiprone. Oral deferiprone was administered to children aged six years and above. From 2018, under the NHC scheme, deferasirox became the first-line iron chelator for children aged 2 to 6 years old. Desferrioxamine is administered through subcutaneous infusion using a portable infusion pump. The restricted accessibility of the infusion pump, primarily due to cost constraints, results in many patients receiving intravenous infusions of desferrioxamine in a hospital setting. Additionally, in some hospitals, red blood cell transfusions are provided in an inpatient setting and the cost of desferrioxamine intended for home administration for the month is included in the hospital admission costs. Consequently, the cost of iron chelation comprises a substantial portion of the overall hospital admission costs.

In the results, there is no way to separate whether the same patient had several hospitalizations, which could determine an analysis bias. These intestinal infections are all related to thalassemia, the description of the article is not clear.

Author’s reply:

We thank the reviewer for the comments. The information obtained through ICD codes presented limitations related to data completeness, including distinguishing whether the same patient had multiple hospitalizations and the details of co-diagnoses. We clarified this important point in the discussion part.

Page 8, Lines 248-251

Original:

“The retrospective nature of this study introduced limitations related to data completeness,…..”

Revision:

" The retrospective nature of this study introduced limitations related to data completeness, including the number of hospitalizations from the same patient and the details of co-diagnoses,…."

In the discussion, the articles cited only investigated children too, it was not clear. Treatment of thalassemia with transfusion is normally outpatient.

Author’s reply:

We thank the reviewer for the valuable comments. We primarily cited articles that focused on pediatric patients with thalassemia [references 8-15] to compare them with the pediatric patients in our study.

In Thailand, some hospitals provide red blood cell transfusions in an inpatient setting. However, we lack information on the proportion of hospitals that offer transfusions as outpatient or inpatient services.

Perhaps the inclusion of neonatal screening as a cost reduction strategy should be addressed in the discussion and conclusion, including cost reduction.

Author’s reply:

Thank you for the comments and suggestions. We included a discussion of both prenatal screening and neonatal screening programs.

Page 7, Lines 237-243

“While a successful universal screening program for couples at risk of fetal severe tha-lassemia diseases, including beta-thalassemia major, beta-thalassemia/Hb E disease, and Hb Bart’s hydrops fetalis, has been implemented in Thailand [23], neonatal screening is not currently available. The establishment of universal neonatal screening for thalassemia in Thailand could play a significant role in the early diagnosis of severe thalassemia not screened prenatally, as well as milder forms of thalassemia. and improved management, leading to better outcomes.”

Thank you very much for your kind consideration. I look forward to the comments and suggestions.

Yours sincerely,

Pimlak Charoenkwan, M.D. (Corresponding author)

Associate Professor

Division of Hematology and Oncology,

Department of Pediatrics,

Faculty of Medicine, Chiang Mai University

Chiang Mai 50200, Thailand

Tel: +66-53-935412

Fax: +66-53-936461

Email address: [email protected]