Overview Of The Disease Thalassemia Biology Essay


Thalassemia is a progressive global public health problem with an estimated 900,000 births of clinically significant thalassemia disorders expected to occur in the next 20 years. Approximately 3% of the world population is carrier of a β- thalassemia gene mutation. Primary preventive strategies against β-thalassemia trait serve as the backbone, especially in countries with high prevalence. Majority of the countries lying in the β-thalassemia prevalent belt (extending along the Mediterranean Sea) are resource-limited. Prevalence of thalassemia in Pakistan is reported in the range of 3-8%.The β-thalassemia is characterized by hypochromic microcytic anemia. Iron deficiency is among most prevalent cause of hypochromic microcytic anemia in Pakistan. The β-thalassemia cases are usually treated with iron supplements leading to clinically complicating iron overload. Differentiation of these two types of anemia is very important because of altogether different management strategies.

The aims of the present study was to compare the effectiveness of various screening tests in predicting BTT for hypochromic microcytic cases, (which were later confirmed by increased HbA2 levels on cellulose acetate electrophoresis) and to establish a simple, cost effective, rapid to perform, reliable, sensitive & specific mass screening tool for BTT detection for the foreseeable future.

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Total 253 cases with microcytosis (MCV ≤ 80fL) and 250 controls (MCV ≥ 80fL) based on results of automated hematology analyzer (Celltac- α) at Dow Diagnostics Research & Reference Lab (from December 2009 to August 2010) were screened for β-Thalassemia Trait (BTT). The five Discriminant functions (DF) were evaluated for all cases to separate BTT and Non BTT cases. The DF were DF1 = RBC count, DF2 = MCV2xMCH/100, DF3 = MCV/RBC DF4 = MCH/RBC and DF5 = HBx5+RBC+3.5. All the cases were screened with Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT) and confirmed for increased HbA2 by electrophoresis at alkaline pH.


Mean Haemoglobin was 10.91 ± 2.31g/dl in BTT with mild anemia, Mean MCV and MCH were 62.32 ± 6.38fL and 20.2 ± 2.79pg in BTT respectively. Mean RBC count was 5.3± 1.26 X 1012 / L in BTT. DF's showed variable degree of sensitivity, specificity and positive predictive value. NESTROFT found to be 92.3% sensitive with specificity, Positive predictive value (PPV) and Negative predictive value (NPV), 86.5%, 89.55% and 90% respectively.

Shine & Lal index was most sensitive (96.9%) among discrimination function in differentiation of BTT from IDA followed by Mentzer Index (78.4%).

Interpretation and Conclusion

Differentiation of BTT from non BTT can be effectively established patients with microcytosis (MCV ≤ 80 fL) by routine hemogram data i.e., a raised RBC count (> 5 x 1012/L), with mild anemia and a set of cost effective screening test like DF3 (MCV/ RBC), DF5 (Hbx5+RBC+3.5) complemented by NESTROFT.


β-thalassemia trait; discriminant functions; electrophoresis; iron deficiency anemia; NESTROFT.

Chapter 1




The term Thalassemia is derived from Greek word 'thalassa' that means the sea referring to Mediterranean Sea and 'mia' means blood. It is also called Mediterranean anemia or Cooley's disease because it is endemic in regions of Mediterranean, Africa, Southeast Asia, Southern China, India and Pakistan.(1) Thalassemia is an autosomal recessive disease, in which defective synthesis of globin genes that make up hemoglobin thus results in quantitative defects causing anemia. It is the most common hemoglobinopathy worldwide with carrier rate of 1.7% and high prevalence in Asia including Pakistan, comprising of nine million carriers result in more than 5000 transfusion dependent children every year.(2, 3, 4)

Pakistan is under developed and resource limited country. Such high burden of disease not only causes economical and emotional strain on affected families but also to the nation at large. Average annual funds needed for each thalassemic major child is more than 50,000 PKR for blood transfusion and multiple drugs.

There is lack of proper public awareness regarding disease of such high magnitude; there is increasing number of consanguinity result in escalation of thalassemia burden. Thalassemia can effectively be prevented by awareness, mass screening, genetic counseling and prenatal diagnosis. There is significant need for public awareness and screening programme to prevent further births of thalassemia major children. (3)

Screening tests for β-thalassemia trait (BTT) detection such as determination of red cell indices, haemoglobin A (HbA), haemoglobin A2 (HbA2), and Foetal haemoglobin (HbF) level estimation are time consuming and expensive for population screening. Therefore, there is dire need for a simple, low cost, rapid and reliable technique for the screening of the masses. (5)

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In Thalassemia red cells appears to be microcytic and hypochromic usually with mild degree of anemia. Iron deficiency anemia (IDA) also causes microcytic hypochromic anemia, which is prevalent in Pakistan. The screening test must be able to efficiently differentiate between BTT and IDA. Therefore, accurate diagnosis of carriers may prevent the further spread of disease.

The objectives of this study were to screen for BTT in subjects with hypochromia & microcytosis, to evaluate a different screening test in differentiating between BTT and IDA and aim was to establish a simple, efficient and economical test for mass screening of BTT.

Statement of the problem

Do current screening methods are effective for BTT detection?

Rationale of the study:

The prevalence of thalassemia is high in Pakistan due to consanguineous marriages being common. The marriage of subjects with BTT results in probable thalassemia major child. Thalassemia is easily preventable disease by avoiding such marriages. The most of the children with thalassemia are born in low-income countries. The blood transfusion needed to all thalassemia major patients but majority of these patients do not get it. The most of the transfused patients develop serious complication due to iron overload.(6) There is a strong need for combined treatment prevention programmes to prevent patients' embarrassing situation.(7) The combined programmes results in improvement in survival of these patients.(8, 9) The affected births are falling and numbers of patients are gradually stabilizing.(10-13)

The prevention programmes are effective because of its demonstrable cost-effectiveness, and thalassaemia is gradually becoming contained.(7)

At present expansive bone marrow transplantation with compatible sibling donors is the only available cure for limited number of thalassemia patients. Although much of work is under process for curative gene therapy or other approaches to genetic manipulation, but it will take considerable time before they are implemented as protocol into clinical practice and that, majority of patients will not be affording likely to be extremely expensive therapy will be only available to richer countries.(14) Hypochromic microcytic anemia comprise majority of anemia. It is necessary to differentiate the causes precisely since the therapeutic approach is different for each.

The information obtained by this study may help in efficient prevention of thalassemia.

Significance of the problem

According to data published by the World Health Organization (WHO), prevalence of carriers for hemoglobinopathies all over the world is 269 million.(15) The Prevalence of thalassemia reported approximately 5.6% in Pakistan.(3) BTT is characterized by hypochromic microcytic anemia. Iron deficiency is among the most prevalent causes of hypochromic microcytic anemia in Pakistan. BTT cases are usually treated with iron supplements leading to complicating iron overload. Differentiation of these two types of Anemia is very important because of differing management strategies.(16) There is need to improve patient care by promoting the best practices in thalassemia prevention and prenatal diagnostic options and to establish a simple, cost effective, rapid, reliable, sensitive as well as specific mass screening tool for BTT detection for the foreseeable future.

Study Hypothesis

Ho (Null hypothesis): No statistically significant differences occur among various screening strategies for the detection of BTT.

Operational Definitions

β-Thalassemia: A quantitative defect in the production of normal adult hemoglobin due to genetic defects; leading to a state of low hemoglobin level.

NESTROFT. 'Osmotic fragility test on red blood cells for detection of abnormal hemoglobin '

Microcytosis: A morphological pattern of red cell on stained peripheral smear, whereby red cell appears to be smaller in size then the normal for that specific age and gender.

Hypochromia: A morphological pattern of red cell on stained peripheral smear, whereby red cells appear to have larger the normal area of central pallor due to lack of appropriate concentration of hemoglobin

Hemoglobin electrophoresis: A test to detect the level of different variants of hemoglobin in patients.


Iron deficiency anemia is common in Pakistan.

NESTROFT is an efficient tool for mass screening of BTT.

Discriminant functions can screen BTT if combined with NESTROFT.