Thalassemia screening should be mandatory
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
Vice President, AGD Biomedicals (Pvt) LTD.
Thalassemia major is an inherited disorder of red blood cells. Being an important cause of morbidity and mortality, it imposes a heavy burden on families and the health sector in India and other countries in the world(4, 5). Thalassemia screening tests before marriage should be mandatory, since, it is a genetic blood disorder that can be passed from parents to children(1,9). If both parents are carriers of the thalassemia minor gene, there’s a risk of their child inheriting the more severe form, thalassemia major (TM)(1). TM children require life-long blood transfusions and supportive therapies. Untreated TM child results in death in early childhood. Raising a TM major child has a significant financial impact. Early screening for thalassemia is extremely cost effective and helps parents prepare for alternative plans to prevent birth of thalassemia major child(15). Accurate and precise screening of thalassemia is possible by the determination of complete blood count (CBC); using Indigenous Hematology analyzer such as HT 340(14).
NOTE:
(1) The 2021 Global Burden of Disease Survey indicates that 1.31 million persons worldwide had severe thalassemia while thalassemia trait occurred in 358 million persons. Every year Thalassemia major cases cause average 11,100 deaths(3,6,7).
Q1. What are thalassemia disorders?
ANS: Thalassemias are hereditary hemoglobin synthesis disorders. These are of two types: α-Thalassemia and β-thalassemia.
NOTE: The main components of normal hemoglobin molecule are α-units and β-units respectively. Genetic mutations of α-unit lead to α-Thalassemia and that of β-unit lead to β-thalassemia(14).
Q2. What is the treatment for raising a TM child?
ANS: Caring for a child with TM involves ongoing medical management, including life-long blood transfusions for anemia treatment and iron chelation therapy to remove excess iron from those transfusions. Other treatments include infection prevention drugs, hormone therapy (if necessary), additional supportive medications, frequent laboratory tests, radiology investigations, dental investigations, travel expenses, etc.
Q3. What are the side-effects of long-term therapy to treat a TM child?
ANS: Long-term blood transfusions cause iron overload, leading to severe damage to vital organs like the liver, heart, liver, and endocrine glands. TM child suffers from stunted growth, delayed sexual development, formation of brittle and deformed bones, splenomegaly (enlarged spleen), irregular heartbeat, and increase in the risk of severe infections.
Q4. What is the significant financial impact of raising a TM child in India?
ANS: Raising a thalassemia major child has a significant financial impact, with costs in India from ₹66,000 to over ₹500,000 annually per child. Taking into account a 10% inflation rate each year, this expense is projected to rise annually. TM child families face substantial out-of-pocket expenses, which can lead to severe financial distress, debt, and experience of catastrophic healthcare expenditure(15).
Q5. What are the IVD Clinical laboratory tests that give accurate and precise diagnosis of thalassemia?
ANS: The following tests are recommended for Thalassemia detection:
THALASSEMIA TEST PANEL(14)
(A) CBC with additional screening using Metzer Index (MI)
(B) HPLC or Electrophoresis test
(C) If necessary Additional test: DNA sequencing
NOTE:
Microcytic hypochromic anemia could be observed in Thalassemia minor (TM) as well as in Iron Deficiency Anemia (IDA) by CBC test. Hematology autoanalyzer with facility to determine “Metzer Index” (MI) & “Sehgal Index” (SI) is useful to differentiate TM from IDA.
Metzer Index (MI) = Mean Corpuscular Volume (MCV)/ Red Blood Cell count (RBC)
Sehgal Index (SI) = Mean Corpuscular Volume (MCV) x Mean Corpuscular Volume/ Red Blood Cell count (RBC)
A Mentzer Index of less than 13 and Sehgal Index of less than 970 is indicative of Thalassemia.
BRIEF PROCEDURE
(A) First screening by Complete Blood Count (CBC) on Hematology analyzer, which has facility to determine Metzer Index (MI).
(B) All the suspected cases of thalassemia then confirmed by HPLC or Electrophoresis tests (Refer to Case studies).
(C) DNA sequencing test can identify carriers of thalassemia genes and it is also useful to identify the exact mutation which underlies the disease. This test is useful in case bone marrow transplantation is advised.
Q6. What is the prevalence of thalassemia in India?
ANS: About 10,000 to 12,000 thalassemia children are born annually in India. Very few thalassemia babies are optimally managed(4, 5). There are about 1 to 1.5 lakhs of β-thalassemia children and about 42 million carriers of ß (beta) thalassemia trait. Alpha-thalassemia affects a significant portion of the global population, with estimates suggesting that over 20% of people are carriers of some form of alpha-thalassemia(4,5).
Q7. Why thalassemia screening should be mandatory?
ANS: If both the parents are carriers of thalassemia minor, there is a 25% chance with each pregnancy that the child will inherit thalassemia major. Thalassemia screening is especially important for everyone, since it can detect thalassemia carrier stage and provides a valuable insight into potential genetic risk(14).
Q8. What is the appropriate age for thalassemia detection tests and how these are done?
ANS: Thalassemia detection tests can be done at any age and these require only few milliliters (ml) of random blood(14).
Q9. If both the partners are carriers of the thalassemia gene, what should they do?
ANS: If both the partners are carriers, genetic counseling can provide options such as IVF with genetic testing or prenatal testing to help manage the thalassemia risks(2).
Q10. How long before marriage or pregnancy should a couple undergo thalassemia tests?
ANS: It is necessary to test for thalassemia during school or college days. Otherwise before marriage or during preconception planning, thalassemia tests must be performed so that reasonable time is obtained to explore options and prepare for any potential risks(2).
Q11. What is the importance of genetic counseling?
ANS: Genetic counseling is useful for couples to understand their risk of passing on genetic conditions like thalassemia. A genetic counselor can guide them through reproductive options and provide necessary support(2).
CASE STUDY 1
Blood of a 9-year-old boy was examined for thalassemia detection as a part of routine general medical examination organized by his school. His complete hemogram (CBC) report was as follows:
COMPLETE HEMOGRAM
| TEST | RESULT | REFERENCE RANGE |
| Hemoglobin | 12.8 g/dl | 13–18 g/dl |
| Total erythrocyte count | 5.5 X 1012/l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 7.3 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 68% | 40–75% |
| Lymphocytes | 30% | 20–45 % |
| Eosinophils | 2% | 1–4 % |
| Monocytes | 2% | 2–8% |
| Hypochromia | + | – |
| Microcytosis | + | – |
| Anisocytosis | + | – |
| PCV | 40% | 36–48% |
| MCV | 70 fL | 82–92 fL |
| MCH | 29 pg | 27–32 pg |
| MCHC | 32 % | 32–36 % |
| RDW- CV | 14 | 12–14 |
| Platelet count | 168 X 109/l | 150–400 X 109/l |
| Stained blood smear examination observations | Presence of occasional target cells and poikilocytes | |
| Metzer Index (MI) | 12.7 | |
| HbA2 (Hemoglobin A2) determination (HPLC method) | 4.8% | 1.3- 3.5% |
Significant increase in HbA2
Diagnosis
Patient was a case of thalassemia minor trait.
NOTE: Only by routine CBC test, supportive Hb HPLC and by accurate evaluation of the reports, it was possible to detect thalassemia trait. Counselling is necessary in such case so that in future marriage with a partner having thalassemia trait could be avoided.
CASE STUDY 2
A six-year-old girl was admitted to a hospital since she was suffering from weakness, anorexia, recurrent fever, diarrhea, yellow coloration of eyes and skin, and loss of weight. Her complete hemogram report was as follows:
COMPLETE HEMOGRAM
| TEST | RESULT | REFERENCE RANGE |
| Hemoglobin | 6.3 g/dl | 13–18 g/dl |
| Total erythrocyte count | 2.5 X 1012/l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 5.6 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 65% | 40–75% |
| Lymphocytes | 30% | 20–45 % |
| Eosinophils | 4% | 1–4 % |
| Monocytes | 1% | 2–8% |
| Hypochromia | ++++ | Normal cells |
| Microcytosis | +++ | Normal cells |
| Poikilocytes | +++ | Normal Cells |
| Target cells | ++ | |
| PCV | 20% | 36–48% |
| MCV | 68 fL | 82–92 fL |
| MCH | 20.6 pg | 27–32 pg |
| MCHC | 33 % | 32–36 % |
| RDW- CV | 30.6 | 12–14 |
| Platelet count | 168 X 109/l | 150–400 X 109/l |
| Stained blood smear examination observations | Presence of large number of target cells and poikilocytes | – |
| Hemoglobin fraction by HPLC: | ||
| HbA | 10% | 95-98% |
| HbA2 | 5% | 2.0-3.5% |
| HbF | 80% | <2% |
INTERPRETATION:
On the basis of very low hemoglobin, Total RBC count, MCV, MCH, PCV, and presence of
Microcytes, poikilocytes, target cells and with significant decrease in HbA, and increase in HbF and HbA2 indicate a Case of Thalassemia Major.
References
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(2) “How Can Thalassemias Be Prevented?”. NHLBI. 3 July 2012. Archived from the original on 16 September 2016. Retrieved 5 September 2016.
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(9) Baird DC, Batten SH, Sparks SK (March 2022). “Alpha- and Beta-thalassemia: Rapid Evidence Review”. American Family Physician. 105 (3): 272–280. PMID 35289581.
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(15) Ritu Gupta, Nita Radhakrishnan, Ravi Shankar et. al. Comparative Analysis of the Costof Thalassemia Screening VS Treatment in Different Healthcare Sectors in Delhi National Capital Region. Indian Journal of Public Health Research and Development / Vol. 16 No. 2, April-June 2025.
