To assess iron deficiency anaemia in patients with cyanotic heart disease compared to general population

Objective: Congenital heart disease has an overall incidence of 8 per 1000 live births. It can be grouped into acyanotic congenital heart diseases (without a shunt or with a left to right shunt) and cyanotic congenital heart disease (with a right to left shunt). Cyanotic congenital heart diseases are those inborn lesions of the heart and great vessels in which there is shunting of blood from right side of the heart to the left side with the result that de-oxygenated blood enters the systemic circulation, thereby decreasing its oxygen saturation and causing cyanosis. The commonest of these diseases is Tetralogy of Fallot's. Only a few of these diseases are compatible with life beyond 12 years of age. Methods: The present study was carried out in the department of Pediatrics, Mahatma Gandhi Memorial Medical College, Indore from January 2012 to July 2013 (duration of study was one and half years). During this period thirty children with congenital cyanotic heart disease between 6 months to 5 years of age were included in this study. Blood parameters assessed were Hemoglobin (Hb gm%), Mean Corpuscular Volume (MCV) fl and Ferritin levels. Results: The mean hemoglobin in cyanotic heart disease cases was 13.39 gm/dl with a S.D. of 2.38. In the control group the mean hemoglobin was 9.57 gm/dl with a S.D. of 1.29. Mean MCV in cyanotic heart disease cases was 71.47 fl with S.D. of 9.28 and in controls it was 78.41 fl with a S.D. of 5.87. Mean Ferritin in cases was 41.63 ng/ml with S.D. of 35.04 and in controls it was 78.75 ng/ml with S.D. of 51.40. P value was 0.001 indicating a statistically significant decreased ferritin in cases. Conclusion: Iron deficiency anemia was present in 56.6% of the cases on basis of MCV. The high iron requirements of cyanotic heart disease cases due to increased erythrocytosis induces iron deficiency anemia.There was statistically significant difference in Hb and MCV values between cases and controls. The ferritin level was statistically significantly lower between cases and controls suggesting iron deficient state in CCHD patients. Iron therapy in iron deficient CCHD (based on hematological and iron indices) patients might improve clinical outcome in these patients.


Introduction
Congenital heart disease has an overall incidence of 8 per 1000 live births (Nelson,) [1]. It can be grouped into acyanotic congenital heart diseases (without a shunt or with a left to right shunt) and cyanotic congenital heart disease (with a right to left shunt).
Cyanotic congenital heart diseases are those inborn lesions of the heart and great vessels in which there is shunting of blood from right side of the heart to the left side with the result that de-oxygenated blood enters the systemic circulation, thereby decreasing its oxygen saturation and causing cyanosis [1]. The commonest of these diseases is Tetralogy of Fallot's [2]. Only a few of these diseases are compatible with life beyond 12 years of age. However, with palliative and corrective surgery, the life span of patients with these disorders has been considerably prolonged.
The clinical profile of the various cyanotic congenital heart diseases includes manifestations such as cyanotic spells, exertional dyspnea, growth retardation, repeated chest infections, palpitations, squatting and cardiovascular findings consistent with the heart lesion [1]. Associated secondary polycythemia causes blood hyper viscosity (usually only when the hematocrit is more than 0.65) which causes symptoms such as headache, faintness, dizziness, visual disturbances, fatigue, muscle Pediatric Review: International Journal of Pediatric Research Available online at: www.pediatricreview.in 269|P a g e pain, muscle weakness, depressed mentation [3]. Complications such as coagulation abnormalities can cause hemolysis, epistaxis, easy bruising, gingival bleeding, menorrhagia. Arthralgia and acute gouty arthritis can occur due to hyperuricemia which results from decreased renal uric acid clearance [4]. Children are more prone to cerebrovascular accidents [5]. Acute cholecystitis due to calcium bilirubinate stones can also occur [3].
Hypoxia of the renal tissue releases erythropoietin which stimulates the erythroid marrow to become hyperplastic and red cell mass and total blood volume increases [6]. Platelet counts are often moderately reduced but more important is a qualitative platelet hemostatis defect Upto a point the increase in red cell mass enhances oxygen transport and delivery. But the increased number of red cells also cause a rise in the packed cell volume (hematocrit) thereby increasing the whole blood viscosity, which if excessive, affects blood flow and, therefore tissue perfusion. In cases in which blood hyper viscosity itself starts causing symptoms of decreased tissue blood flow, phlebotomy becomes a therapeutic necessity [3]. Polycythemic patients often get rapid relief of symptoms from venesection therapy, presumably from lowering of their whole blood viscosity, but later on identical symptoms recur at lower haemoglobin concentrations in patients who have been made severely iron deficient (thereby causing hypochromic microcytic anaemia) following repeated vene sections [7] and other causes of iron deficiency.
It is believed that the combination of the high red cell mass and known decreased deformability of iron deficient red blood cells [8] may lead to a "secondary hyper-viscosity syndrome" in these patients.
The hyper viscosity symptoms of iron deficiency and polycythemia induced hyper viscosity are indistinguishable clinically. But if hyper viscosity symptoms are present with hematocrit levels less than 0.65 iron deficiency should be suspected as the cause and phlebotomy under these circumstances aggravates the symptoms.

Materials and Methods
Place of study: Department of Pediatrics, Mahatma Gandhi Memorial Medical College, Indore from January 2012 to July 2013 (duration of study was one and half years).

Type of study: Observational study
Inclusion criteria: Congenital cyanotic heart disease between 6 months to 5 years of age were included in this study. The mean hemoglobin in cyanotic heart disease cases was 13.39 gm/dl with a S.D. of 2.38. In the control group the mean hemoglobin was 9.57 gm/dl with a S.D. of 1.29. The t value was 7.7 and p value was 0.034 indicating a statistically significant increased hemoglobin levels in cyanotic heart disease cases.

Discussion
Maximum number of patients (70% of cases) belonged to age group between 6 months to 1 year. 17% belonged to age group 13 months to 24 months. 13% belonged to age group 25 months to 60 months.
Lango et al [16] found male female ratio in his study on cyanotic heart disease patients to be 52:48. 50% cases were from rural areas and 50% from urban areas. 37% of total cases were females below 1 year of age. 33% of total cases were males below 1 year of age. 80% of cases between1 to 2 years of age were females. Between 2 to 5 years of age 100% of cases were males.
The mean hemoglobin in cyanotic heart disease cases was 13.39 gm/dl with a S.D. of 2.38. In the control group the mean hemoglobin was 9.57 gm/dl with a S.D. of 1.29. Pvalue was 0.034 indicating a statistically significant increased hemoglobin levels in cyanotic heart disease cases.
Koeffler and Gold Wasser [9] and Erslev and Karo [10] observed renal hypoxia causes erythropoietin release which stimulates the erythroid marrow to become hyperplastic thereby raising the red cell mass [6].
Jha et al [11] in Central India found mean hemoglobin in cyanotic heart disease cases to be 11.0 gm%. Cemile et al (1999) [12] in Ankara, Turkey found mean hemoglobin to be 14.8 gm%. MAmoozgar [13] Iran found mean hemoglobin in cyanotic heart disease patients to be 16.0gm%. OO Ogunkule [14] in his study in Nigeria found mean hemoglobin to be 17.0gm% Mean MCV in cyanotic heart disease cases was 71.47 fl with S.D. of 9.28 and in controls it was 78.41 fl with a S.D. of 5.87. P value was 0.01 showing a statistically significant decreased MCV in cyanotic heart disease cases. Jha et al [11]in Central India found mean MCV value in cyanotic congenital heart disease to be 76.4 fl. M Amoozgar [13], Iran found mean corpuscular volume in cyanotic heart disease patients to be 73.8 fl OO Ogunkule [14] in his study in Nigeria found mean corpuscular volume to be 80.7 fl.
Cemile et al [12] in Ankara, Turkey found mean corpuscular volume to be 77.5 fl. Olcay et al [15] in Turkey in his study to compare hematological parameters between iron sufficient and iron deficient cyanotic heart disease patients found mean MCV to be 83. Olcay et al [15] in Turkey in his study to compare hematological parameters between iron sufficient and iron deficient cyanotic heart disease patients found mean Ferritin to be 37.2 ng/ml in iron sufficient group and 7.5 ng/ml in iron deficient group. Cemile et al [12] in Ankara, Turkey found mean Ferritin to be 39.2 ng/ml. Lango [16] in Kenya found mean Ferritin to be 48.9 ng /ml.
This study stresses on the fact that iron deficiency anemia is a relative iron deficiency state. Hemoglobin may be normal but red blood cells are microcytic hypochromic in nature which suggests iron deficiency anemia. This could be further confirmed by ferritin levels which are relatively low than general population.
The use of iron therapy in children with cyanotic heart disease will alleviate iron deficiency symptoms and will improve overall well being in these patients.
Recommended dose of iron is 3 -5 mg /kg / day.

Conclusion
Iron deficiency anemia was present in 56.6% of the cases on basis of MCV. The high iron requirements of cyanotic heart disease cases due to increased erythrocytosis induces iron deficiency anemia. There was statistically significant difference in Hb and MCV values between cases and controls. The ferritin level was statistically significantly lower between cases and controls suggesting iron deficient state in CCHD patients. Iron therapy in iron deficient CCHD (based on hematological and iron indices) patients might improve clinical outcome in these patients.

Recommendations
The ferritin level was statistically significantly lower between cases and controls suggesting iron deficient state in CCHD patients. Iron therapy in iron deficient CCHD (based on hematological and iron indices) patients might improve clinical outcome in these patients.
Blood parameters should be regularly monitored in cyanotic congenital heart disease patients.
Proper feeding, treatment of paristitic infections, timely weaning are other contributing factors for anemia and iron deficiency states as in general population which too should be given utmost priority.
Source of funding: none, in house investigatory facilities were used and outsourcing was utilized as per the institutional norms.
Funding: Nil, Conflict of interest: None initiated, Perission from IRB: Yes