FREQUENCY OF IRON OVERLOAD COMPLICATIONS IN BETA THALASSEMIA MAJOR PATIENTS.
Key Words: Thalassemia major, Hypocalcemia, Hypothyroid, Short stature, Diabetes mellitus
Inherited hemoglobin (Hb) disorders rank first among the single-gene disorders1. These are significant health problems worldover with more than 330,000 infants born with these disorders annually; 17% of these infants are sufferers of thalassemia. Thalassemias are recessively inherited disorders of Hb synthesis where decreased synthesis of the ss-globin chain occurs. The homozygous state leads to severe anemia requiring regular blood transfusion2. When beta thalassemia major patients are transfused poorly or left untreated, they present as retarded growth, anemia, jaundice, weak musculature, knock-knee, liver and spleen enlargement, ulceration on the leg, development of masses from extramedullary hemopoeisis and changes in skeleton from bone marrow expansion3-5. Patients of this category present usually in the first year of life and if left untreated they die within 5 years of life.
Blood transfusions given at frequent intervals prolong the life of patients and are the mainstay of treatment. Although transfusions are life savers for such patients but at the same time lead to iron overload and expose the patients to many other complications like hypersplenism, chronic hepatitis, human immuno-deficiency virus (HIV), venous thrombosis and osteoporosis6.
Iron overload is among the most serious issues of transfusion-dependent patients and its complications are the most significant cause of death. Iron overload in these children lead to retardation of growth and sexual dysfunction. Complications of iron overload later on include cardiac problems, hepatic dysfunction and endocrine problems. Many mechanisms have been proposed so far for elaboration of glandular damage occuring via iron overload7.
This study was done to find out the frequency of iron overload complications like short stature, hypothyroidism, hypoparathyroidism, cardiac dysfunction and diabetes mellitus in beta thalassemia major patients on chelation therapy in our set up where data is scarce.
This was a cross-sectional study done in Fatimid Foundation, Peshawar from June 2015 to August 2015. The population of this study comprised of 1500 patients of beta thalassemia major registered at Fatimid Foundation, Peshawar. Sample size was calculated to be 100 by Raosoft online sample size calculator with 7.95% margin of error, 90% confidence interval and 50% response distribution. Consequently, 100 patients of beta thalassemia major, aged 5-20 years whose diagnosis was confirmed by Hb electrophoresis and who were on regular transfusion and chelation therapy attending Fatimid Foundation, Peshawar were included in the study. Consecutive non-probability sampling technique was done. Ethical approval was taken for the study. Patients who were very ill, receiving calcium and vitamin D supplementation or drugs affecting calcium levels were excluded from the study.
Detailed history was taken, examination of the patients was carried out and 5ml of blood was taken from the patients in plain tubes with gel through venipuncture. Blood was allowed to clot and then centrifuged for separating the serum. Serum calcium and phosphorus levels were determined in the obtained sera on semiautomated analyser through commercially available kits. Hypoparathyroidism was labelled as positive in patients having serum calcium level below 8mg/dl and serum phosphate above 5mg/dl. Heights of patients were recorded and those patients whose height was below the 5th percentile for their age, as plotted on the Centers for Disease Control and Prevention (CDC) 2000 age/gender specific growth charts, were labelled as short stature. Thyroid function was evaluated by measurements of thyroid stimulating harmone (TSH) and thyroxin (free T4) using enzyme-linked immunosorbent assay (ELISA) on the obtained serum.
Hypothyroidism was defined by a TSH level >8uIU/ml, and T4 levels 50% of deaths in patients with thalassemia major and are therefore the main determinants of survival9. Cardiac dysfunction may present as hemosiderotic cardiomyopathy, cardiac failure, pulmonary hypertension, arrhythmias, systolic/diastolic dysfunction, pericardial effusion, myocarditis or pericarditis12. Iron overload plays a main role in cardiac dysfunction; though genetics, immunologic factors, infections and chronic anemia are also responsible. Cardiac complications are reported to range from 4.5-23%5,12. The prevalence of cardiac dysfunction in our study was 9% and the heart diseases noted were heart failure, arrhythmias, pericardial effusion and pulmonary hypertension.
Thyroid dysfunction is present in 13-60% of these patients but it is variable in its severity in different surveys. It was reported to be 7% in Shiraz by Karamifar et al20 and 16% in Tabriz by Najafpour et al21 whereas De Sanctis et al22 reported 21.6% in Italy. A high prevalence of subclinical primary hypothyroidism (normal FT4, FT3; increased TSH) has been reported whereas prevalence of overt hypothyroidism (low FT4 and/or FT3; increased TSH) is relatively low22. The frequency of hypothyroidism in our study was 10%.
Although genetic predisposition was described, there was little data on its contribution to diabetes development in thalassemia major23.The prevalence of diabetes mellitus in beta-thalassemic patients is reported up to 24%24. In our study, only 5% of patients were suffering from diabetes. This however may be due to the reason that age limit was 20 years in this study and diabetes is uncommon in beta-thalassemics who are less than 16 years old according to a prior study25.
This study has several limitations. Data on direct measurement of hepatic iron or cardiac MRI was not available. Data on adherence to treatment was unavailable. Due to the fact that it was a single center study with a small sample size, the generalization of results to the whole population was restricted.
The frequency of iron overload related complications in patients of thalassemia major in our setting was different from their incidence reported internationally. Short stature was the most frequent complication in beta thalassemia major patients on transfusion therapy in our set up while diabetes mellitus was the least common complication.
It is important to determine the genetic status of thalassemics of our region which will uncover the genetic modifiers responsible for iron overload mediated organ injury. This may explain the low cardiomyopathy rate and high short stature and hypoparathyroidism rate among our population. The high prevalence of complications in our set up also stresses the need for further improvements in the management of these complex patients.
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|Publication:||Journal of Postgraduate Medical Institute|
|Date:||Mar 31, 2019|
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