The review discusses problem of nutritional anemia
, particularly iron deficiency
with or without anemia
. Critical analysis continues to recommend cyanmethemoglobin method for estimation of hemoglobin; filter paper technique is suited for field surveys. Recently introduced HemoCue method for hemoglobin estimation is practical. However, variability in hemoglobin estimation as compared to cyanmethemoglobin need be evaluated in selected laboratories of the country to derive some form of conversion factor. The red cell indices especially mean corpuscular volume (MCV), percentage mature hypochromic erythrocytes (HyPom), red cell distribution width (RDW) and reticulocyte changes- hemoglobin concentration(CHr) and size(Ret Y), in institutions with modern automated analyzer are of interest as these are more sensitive indices than the hemoglobin level.
, total iron binding capacity and transferrin saturation are not good indicators of iron status. Serum ferritin represents body iron stores; in infection free situation, it is an ideal indicator for diagnosis of iron deficiency and response to iron therapy in community. Recent studies suggest estimation of serum transferrin receptors in addition to serum ferritin in diagnosis of iron deficiency. Bone marrow iron assessment is useful in individual patient; it is not affected by infection. For country like ours, with high prevalence and severity of anemia
, hemoglobin estimation, peripheral smear to exclude malaria
and response to iron therapy remain important time tested tools to diagnose iron deficiency.
iron deficiency, hemoglobin, serum ferritin, transferrin receptors, red cell indices
In India, prevalence of anemia at all ages remains very high e.g. 84.9-86% pregnant women in rural areas are affected and 9.3-9.9% have severe anemia (1,2)
. These studies observed similar prevalence rates for adolescent girls and lactating women. Kapur et al (2002) in an urban slum with ICDS program for 2 decades observed 64% children between 9-36 months of age as anemic with 7.8% having severe anemia (3)
. Eighty eight percent of these children had low serum ferritin. Besides iron deficiency, folic acid
and vitamin B12
deficiencies in early childhood are also common (4)
. Data from US NHANES survey III 1988-94 showed iron deficiency prevalence of 6-18% in children 12-35 months of age. It was observed that anemia is a poor predictor of iron deficiency. The positive predictive value of hemoglobin < 11.0 g/dl was 29 % (95%, CI 20-38%) and sensitivity was 30% (CI 20-40%). If hemoglobin cut off was 10.7 g/dl, the positive predictive value became 38% (CI 24-52%), but lowered the sensitivity to 15% (CI 7- 22%). Most children with iron deficiency are necessarily are not anemic (5)
. Recent studies show that sensitivity and specificity of diagnosing iron deficiency can be improved by assessing transferrin iron saturation, mean corpuscular hemoglobin concentration, and erythrocyte - protoporphyrin, percentage of hypochromic mature erythrocytes (HyPom) or reticulocyte hemoglobin concentration (CHr). However, these changes are indistinguishable to those in chronic disease anemia. The optimal diagnostic approach appears to measure the serum ferritin as an index of iron stores and the serum transferrin receptor as an index of tissue iron deficiency (6)
. The available approaches in diagnosing iron deficiency are discussed in this review.
Iron nutritional status:
In normal individuals, 2/3 of total body iron is available for hemoglobin formation. The remaining 1/3 gets deposited as hemosiderin and ferritin. This can be mobilized when iron is needed in functionally active form. Normal women for pregnancy need around 1000 mg of iron. Iron stores in healthy full term can meet the infants iron requirements until 4-6 months of age. Infant increases body weight and blood
volume by 3 times with increase in total body iron by two times, by the first birthday. However preterm and low birth weight babies having poor iron stores, become deficient earlier (within first 2 months of age). In maternal iron deficiency, there is proportionately less iron transfer to fetus (7,8)
. Nature tries to compensate by secreting more iron in breast milk of the iron deficient mothers (9)
. Intrauterine and early life iron deficiency reduces brain iron content and alters neurotransmitters irreversibly, affecting mental functions (10)
is defined as a condition in which there are no mobilizing iron stores, causing a compromised supply of iron to tissues, including the red cells. It varies greatly with each stage of the life cycle, in general growing children (up to 2 yr of age), pregnant and lactating women and adolescents (second growth spurt) are the most vulnerable. In iron deficiency, hemosiderin and ferritin (iron stores) decrease; supply of iron to the transport protein (apotransferritin) gets compromised, resulting in decrease in transferrin saturation and increase in transferrin receptors.
Stages in iron deficiency: (11)
First stage - depletion as storage iron is observed as fall in serum ferritin (reflects low iron in liver/spleen/bone marrow). There is generally absence of stainable iron in bone marrow during rapid growth period. Second stage - decrease in transport iron, results in low serum iron, increased total iron binding capacity and decrease in transferrin saturation. Both these stages are pre-anemic (Latent iron deficiency). Third stage - there is significant fall in supply of transport iron, restricting hemoglobin synthesis with increase in erythrocyte-porphyrin. Microcytosis appears, accompanied with hemoglobin fall to fulfill the laboratory definition of anemia. Iron deficiency as a steady state - as mild deficiency develops very gradually, and is almost in equilibrium due to conditions lasting for months or years. The laboratory values for serum ferritin and transferrin saturation are in normal limits, but such patients respond to iron therapy.
Iron overload syndrome:
or hemochromatosis (primary or secondary), affects liver, pancreas, heart, endocrine glands and skin. Serum ferritin and transferrin saturation are raised, while erythrocyte-protoporphyrin, MCV and hemoglobin remain in normal range.