31.9.45 Serum Ferritin Status and Chelation Therapy of Children and Adolescents with Transfusion Dependent Thalassemia Major in Mirpur, AJK

Original Article

 

Serum Ferritin Status in  Thalassemia Major

Serum Ferritin Status and Chelation Therapy of Children and Adolescents with Transfusion Dependent Thalassemia Major in Mirpur, AJK

Saba Haider Tarar1, Waseem Ahmed Khan2, Iftikhar Ahmed1 and Shakil Asif3

ABSTRACT

Objective: To assess the serum Ferritin levels and chelation therapy in transfusion dependent Thalassemia major children and adolescents in Divisional Headquarters Teaching Hospital, Mirpur, AJK.

Study Design: Descriptive Observational Study

Place and Duration of Study: This study was conducted at the Thalassemia Center of Divisional Headquarters Teaching Hospital, Mirpur, AJK from Oct, 2019 to March, 2020.

Materials and Methods: After taking permission from hospital ethics committee, children with transfusion dependent Thalassemia aged up to 18 years were added in the study after informed written consent. Blood samples were sent for Serum Ferritin levels. Serum Ferritin measurement was done by indirect ELISA kit. Chelation therapy was assessed in terms of Deferasirox Tablets and Desferrioxamine injection.  Data were analyzed on SPSS 20 and the correlation between age, gender, serum Ferritin level and chelation therapy were checked.

Results: A total of 100 children registered with Thalassemia center, Divisional Headquarters teaching hospital, Mirpur were included in this study. There were 55 (55%) males and 45 (45%) females. There were 18 (18%) children between 1-3 years, 20 (20%) in 4-5 years, 17 (17%) in age group 6-8 years, 30(30%) in 9-15 years and 15 (15%) above 15 years of age. Serum Ferritin monitoring revealed 29 (29%) children having Serum Ferritin level between 500-2500ng/dl, 16 (16%) between 2501-3500ng/dl, 19 (19%) between3501-5000ng/dl, 26(26%) between 5001-9000ng/dl and 10 (10%) were having above 9000ng/dl. Maximum children (29%) were found in 500-2500ng/dl serum Ferritin. Majority (66%) was taking chelation as compared to 34% who were not taking any chelation. A strong association was present between Child’s age and serum Ferritin levels with P-value < 0.001. With increasing age, more number of children were taking chelation as compared to younger age (93.33%) at 15 years of age as compared to (45.00%) at 4-5 years of age. Comparing Gender versus chelation revealed that more females i.e. 33 (73.33%) out of 45 were taking chelation as compared to males (60%) taking chelation. It was observed that chelation percentage increased with increasing Ferritin level with P-value < 0.004.

Conclusion: The average serum Ferritin levels are significantly raised as compared to the normal permissible levels in these patients. This is further made worse by the fact that around one third of them are not receiving any kind of iron chelation therapy.

Key Words: Thalassemia, Ferritin, Chelation, AJK

Citation of article: Tarar SH, Khan WA, Ahmed I, Asif S. Serum Ferritin Status and Chelation Therapy of Children and Adolescents with Transfusion Dependent Thalassemia Major in Mirpur, AJK. Med Forum 2020;31(9):194-198.

 

 

INTRODUCTION

 

 

1. Department of Pediatrics / Ophthalmology2 / Psychiatry3, Divisional Headquarters Teaching hospital/ Mohtarma Benazir Bhutto Shaheed Medical College (MBBS, MC), Mirpur, AJK.

 

 

Correspondence: Saba Haider Tarar, Assistant Professor, Pediatrics, Divisional Headquarters Teaching hospital/MBBS, MC, Mirpur, AJK.

Contact No: 03015634943

Email: saba_tarar80@yahoo.com

 

 

Received:    May, 2020

Accepted:    July, 2020

Printed:        September, 2020

 

 

 

Thalassemia is one of the genetically acquired disorders of defective globin chain synthesis, resulting in imbalance between the alpha and beta globin chains present in Hemoglobin1. Globally around 70,000 new children are born with different types of Thalassemia annually.2Thalassemic children who are transfusion dependent generally require monthly RCC (red Cell concentrate) transfusions resulting in excessive iron load on the body.

Every single unit of packed RCC produces 200mg of free iron in human body.3

During normal condition, iron binds with a carrier protein Transferrin which transports iron in various tissues. However, if there is excessive iron in the body due to any cause, Transferrin becomes fully saturated leaving free iron in blood circulation. Free iron radicals are highly toxic and generate reactive oxygen forms which can badly damage various organs.4 Vital organs damage like liver, heart and endocrine glands is the leading cause of complications, disability and even death of children in thalassemia.5 There are many investigations both invasive as well as non-invasive to check iron status of Thalassemia patients, however serum Ferritin is the readily available and cheap method. Iron Chelation therapy (ICT) is started in all patients generally after 1-2 years of RCC transfusions with a target to keep serum Ferritin < 1000 µg/l. Excessively high values of serum Ferritin crossing 2500 µg/l can lead to vital organ damage especially heart, liver and endocrine glands.6 Regular blood transfusions in Thalassemia patients demand continuous Iron Chelation Therapy (ICT) to avoid the excessive iron load which can lead to cardiomyopathy and decreased cardiac output. This can even decrease total life expectancy of these patients and may have high mortality. 7 On the other hand, this ICT therapy is very expensive and time consuming as well and put another financial burden on these patients. Deferasirox, a novel oral chelator, although effective and easy to administer but it is quite expensive and poses a considerable financial risk as it has to be given daily and lifelong.8Deferoxamine (DFE), the traditional ICT, being given parenterally is being used for more than 4 decades. It is found to be quite effective iron chelator but needs assistance as well as long time for administration.9 It is found that Thalassemia patients are still unable to attain the optimum levels of Serum Ferritin so mostly a combination of chelators is used to control serum Ferritin levels.10

MATERIALS AND METHODS

In this study, we enrolled children suffering from Transfusion dependant Thalassemia aged less than 18 years registered with Thalassemia center of Divisional headquarters teaching hospital. A well-informed written consent was taken. Patients who were undergoing regular blood transfusions monthly for last 2 years were recruited in the study. Blood samples were sent for Serum Ferritin assays. Serum Ferritin levels were done by indirect ELISA kit. Chelation therapy was assessed in terms of Deferasirox Tablets as well as Deferoxamine injections.  Data were analyzed on SPSS 20 and the association between age, gender, serum Ferritin level and whether taking chelation therapy or not were established.

RESULTS

A total of 100 children registered with Thalassemia center, Divisional Headquarters teaching hospital Mirpur were included in this study. There were 55 (55%) males and 45 (45%) females. Age was divided in further subgroups for analysis purpose. There were 18 (18%) children between 1-3 years, 20 (20%) in 4-5 years, 17 (17%) in age group 6-8 years, 30(30%) in 9-15 years and 15 (15%) above 15 years of age.

All Thalassemia patients were having high serum Ferritin. Serum Ferritin monitoring revealed 29 (29%) children having Serum Ferritin level between 500-2500ng/dl, 16 (16%) between 2501-3500ng/dl, 19 (19%) between3501-5000ng/dl, 26(26%) between 5001-9000ng/dl and 10 (10%) were having above 9000ng/dl. Maximum children (29%) were found in 500-2500ng/dl serum Ferritin.

Table No.1: Serum Ferritin Status:

 

 

Frequency

Percent

Cumulative Percent

Valid

 

 

 

500-2500

29

29.0

29.0

2501-3500

16

16.0

45.0

3501-5000

19

19.0

64.0

5001-9000

26

26.0

90.0

>9000

10

10.0

100.0

Total

100

100.0

 

Figure No. 1: Ferritin Status with Frequency

Table No.2: Chelation status

 

 

Frequency

Percent

Valid Percent

Cumulative Percent

Valid

Yes

66

66.0

66.0

66.0

No

34

34.0

34.0

100.0

Total

100

100.0

100.0

 

The statistical analysis revealed a strong association between Child’s age and serum Ferritin levels with P-value < 0.001.

Table No.3: Child's Age * Ferritin status Cross – tabulation

Ferritin Level

 

500-2500 ng/dl

2501-3500 ng/dl

3501-5000

ng/dl

5001-9000 ng/dl

>9000 ng/dl

total

Child's Age

1-3yr

8

6

4

0

0

18

4-5Yr

10

3

4

2

1

20

6-8yr

3

2

4

5

3

17

9-15yr

5

4

4

15

2

30

15yr

3

1

3

4

4

15

Total

29

16

19

26

10

100

As far as Chelation Status was concerned, Majority (66%) was reportedly taking chelation in the form of tab. Deferasirox and Injection Desforaximine as compared to 34% who were not taking any chelation despite counseling.

Table No.4: Chi-Square Tests

 

Value

Df

Asymp. Sig. (2-sided)

Pearson Chi-Square

33.779a

16

.006

Likelihood Ratio

37.284

16

.002

Linear-by-Linear Association

17.923

1

.000

N of Valid Cases

100

 

 

         19 cells (76.0%) have expected count less than 5. The minimum expected count is 1.50.

Figure No.2: Association of Gender with Ferritin level

Males were having high serum ferritin levels as compared to female children in our study.

Association of age of child with chelation:

Table No.5: Child's Age * chelation status Cross Tabulation

Chelation status

 

yes

No

Total

Child's Age

1-3yr

10

8

18

4-5Yr

9

11

20

6-8yr

11

6

17

9-15yr

22

8

30

15yr

14

1

15

Total

66

34

100

Table No.6: Ferritin status * chelation status Cross Tabulation

Chelation Status

 

Yes

No

Total

Ferritin status

500-2500

14

15

29

2501-3500

11

5

16

3501-5000

15

4

19

5001-9000

18

8

26

>9000

8

2

10

Total

66

34

100

 

It was observed that with increasing age, more number of children were taking chelation as compared to younger age (93.33%) at 15 years of age as compared to (45.00%) at 4-5 years of age.

Cross-tabulating Gender versus chelation revealed that more females i.e. 33 (73.33%) out of 45 were taking chelation as compared to males (60%) taking chelation. It was observed that chelation percentage increased with increasing ferritin level with P-value < 0.004. however, there was one exception in 500-2500ng/dl ferritin level.

Figure No.3: Ferritin Status with Count

DISCUSSION

It is estimated that the patients suffering from Thalassemia Major receive approximately 20 times higher intake of free iron, so excessive iron load is already anticipated in them. Serum Ferritin assays are the most commonly used method for the estimation of iron overload in these patients as it is simple, cheap and readily available worldwide.11A total of 100 children registered with Thalassemia center, Divisional headquarters teaching hospital Mirpur were included in our study. There were 55 (55%) males and 45 (45%) females. Age was divided in further subgroups for analysis purpose. There were 18 (18%) children between 1-3 years, 20 (20%) in 4-5 years, 17 (17%) in age group 6-8 years, 30(30%) in 9-15 years and 15 (15%) above 15 years of age.

All Thalassemia patients were having high serum Ferritin. Serum Ferritin monitoring revealed 29 (29%) children having Serum Ferritin level between 500-2500ng/dl, 16 (16%) between 2501-3500ng/dl, 19 (19%) between3501-5000ng/dl, 26(26%) between 5001-9000ng/dl and 10 (10%) were having above 9000ng/dl. Maximum children (29%) were found in 500-2500ng/dl serum Ferritin and mean Ferritin was 3201ng/dl. These very high values depict ineffective and inadequate degree of chelation and put these children at a high risk of developing complications.

 

These results were similar to study done by Mishra et al. where 87.4% of the children had significantly higher Ferritin levels. The mean serum Ferritin level was also similar to our study i.e. 2767.52 ng/ml. In that study, around half of the patients had  serum Ferritin between 1000 to 2500 ng/ml, while rest of the patients had values above 2500 ng/ml.12 Serum Ferritin levels were low in a study done in Sri Lanka where Mean serum Ferritin was 1778(± 1458) µg/l and one third of their patients had normal serum Ferritin.6 A considerably high mean serum Ferritin Value of 9542 ± 782 ng/ml is reported by Al-Zubaidietal which is much higher as compared to our study but no reason has been attributed as a cause of so high Ferritin levels .12

In our study, majority (66%) of patients were taking chelation in the form of tab. Deferasirox and Injection Desforaximine as compared to 34% who were not taking any chelation despite counseling. Similar results were shown by Riazetal. in which 58.2% cases were taking chelation and 41.8% were not taking any chelation.14

The statistical analysis revealed a strong association between Child’s age and serum Ferritin levels with P-value < 0.001. Males were having high serum Ferritin levels as compared to female children in our study but there was no significant statistical analysis. It was observed that with increasing age, more number of children were taking chelation as compared to younger age (93.33%) at 15 years of age as compared to (45.00%) at 4-5 years of age. This is in comparison with Riazetal. who showed that Age and chelation therapy have a significant correlation with Serum Ferritin measurements. This study demonstrated that age in years is directly proportional to the serum Ferritin levels.14

Comparing Gender versus chelation revealed that more females i-e 33 (73.33%) out of 45 were taking chelation as compared to males (60%) taking chelation. It was observed that chelation percentage increased with increasing Ferritin level with P-value < 0.004. However, there was one exception in 500-2500ng/dl Ferritin level. Another study by Faruqietal showed similar results with the mean Ferritin value of 6062.61 + 3641.796 ng/ml. He showed that most of the patients were not receiving adequate ICT. And those patients with less optimal ICT were having high serum Ferritin values.11 This was also in comparison with a study done in Karachi where serum Ferritin levels were comparable to our study (3319.6 ± 1925.8) ng/ml in the chelation group as compared to non- chelation group (5514.8 ± 2383.0) ng/ml.14

CONCLUSION

The high serum Ferritin levels in our study strongly supports the rationale of regular monitoring and follow up regarding adequate chelation to minimize iron overload and associated life-limiting complications. We need to create more knowledge and awareness in the Thalassemia patients about the value of monitoring regular serum Ferritin levels. They should be well aware of the consequences and complications of iron overload. Proper chelation of iron overload could improve the quality of life of these patients.

Limitations:

The dose of Deferasirox and Deferoxamine infusions is not ascertained which is a limitation in our study.

Author’s Contribution:

Concept & Design of Study:

Saba Haider Tarar

Drafting:

Saba Haider Tarar

Data Analysis:

Waseem Ahmed Khan

Revisiting Critically:

Shakil Asif

Final Approval of version:

Waseem Ahmed Khan

Conflict of Interest: The study has no conflict of interest to declare by any author.

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