13.1 Introduction

Iron-deficiency anemia (IDA) is the most common nutritional disorder in the world, constituting a public health condition of epidemic proportions. It particularly affects women in the reproductive age group and young children in tropical and subtropical regions. The World Bank estimates that the direct contribution of IDA to global burden of disease is 14 disability-adjusted life-years per 1000 population. It has the greatest overall effect in terms of ill-health, premature death and lost earnings.

Prevalence

IDA affects over 2 billion people in the world. In the developing countries alone, 370 million women suffer from IDA. The average prevalence is higher in pregnant women (51%) than in the nonpregnant women (41%). The prevalence among pregnant women varies from 31% in South America to 64% in south Asia (Figure 13.1). South and south-east Asia combined contribute to 58% of the total anemic people in the developing world. In North America, Europe and Australia IDA during pregnancy is less common. Even in the USA, about 5% of young children and 5–10% of women of reproductive age suffer from IDA. About 20–30% of pregnant women in low socioeconomic strata in the USA exhibit iron deficiency during the third trimester of pregnancy. Surveys from North America and Europe indicate that, among pregnant women, the prevalence of anemia ranges between 10 and 30%. In the developing countries, the problem of iron deficiency is high. In India about 88% of pregnant women are anemic and in other parts of Asia almost 60% of women are anemic; in China, however, the prevalence does not exceed 40%.

Figure 13.1 Prevalence of anemia in women in different regions.

13.2 Definition and clinical features of iron-deficiency anemia

Anemia occurs when hemoglobin production is considerably reduced, leading to a fall in its levels in the blood. The World Health Organization (WHO) recommends cut-off values to determine IDA in different age, gender and physiological groups (Table 13.1).

Although most anemia is due to iron deficiency, the role of other causes (such as folate and vitamin B₁₂ deficiency or anemia of chronic disease) should be distinguished.

Iron depletion can be categorized into three stages of varying degrees of severity ranging from mild to severe (Figure 13.2).

• The first stage involves a decrease in iron stores, which is diagnosed by a decreased serum ferritin level. Although not associated with adverse physiological consequences, this represents increased vulnerability from long-term marginal iron balance that could lead to severe iron deficiency.
  
• The second stage is characterized by biochemical changes reflecting a lack of iron for normal hemoglobin production. There is decreased tranferrin saturation or increased erythrocyte protoporphyrin, and increased serum transferrin receptor levels.
  
• The third stage of iron deficiency is anemia. In severe IDA the levels of hemoglobin are less than 7 g/dl.

Table 13.1 Cut-off points for hemoglobin values for the diagnosis of anemia

Source: WHO (1972). Reproduced with permission from the WHO.

Iron nutritional status can be assessed by the following biochemical and hematological tests.

Serum iron concentration

In IDA, serum iron may either be low or even normal. It is regulated by reticuloendothelial release. The normal values vary between 50 and 175 μg/dl. There is a considerable diurnal variation; the levels are highest in the morning and lowest during the night. It is reduced in inflammation and malignancy and during menstruation. Therefore, this test cannot be really considered as of real diagnostic value.

Total iron binding capacity

Total iron binding capacity (TIBC) and transferrin saturation indicate iron supply to tissues. The normal value is about 300 μg/dl. TIBC is lowered in chronic disease and raised in iron deficiency.

Figure 13.2 Stages of iron depletion.

Transferrin saturation

This is a ratio (expressed as a percentage) of serum iron and TIBC. The normal value is 33%. In iron deficiency, there is a decreased saturation, while in chronic diseases the saturation is normal.

Protoporphyrin

Protoporphyrin is the precursor of heme. Free red blood cell (RBC) protoporphyrin is raised when there is an insufficient supply of iron for heme synthesis. It is also high in IDA, caused by lead toxicity and other sideroblastic anemias.

Serum ferritin

Serum ferritin reflects the status of total body iron stores. It is generally considered as the test of choice for estimating iron stores. A value below about 10 ng/ml is considered as diagnostic of iron deficiency. However, its levels are raised in inflammation, infections and liver disease. The effect of infections on serum ferritin often limits the usefulness of serum ferritin as a sensitive indicator of iron stores, particularly in areas where the incidence of infections is very high, as in the developing countries of south-east Asia. The criteria generally used to diagnose iron deficiency are listed in Table 13.2.

Transferrin receptors

Transferrin receptors become elevated on cell surfaces and in plasma whenever there is insufficient iron supply to cells or iron depletion. The ratio of transferrin to ferritin may be a good discriminator between iron deficiency and anemia of chronic inflammation.

Table 13.2 Diagnostic criteria for iron-deficiency anemia

Because of the cost implications for multiple biochemical tests, the parameter used to indicate iron status in population studies of IDA is measured by hemoglobin.

Clinical features of iron-deficiency anemia

The symptoms of IDA depend on the rate at which anemia develops in an individual. Symptoms may relate to rate of fall in hemoglobin. Since lowering of hemoglobin affects oxygen carrying capacity, in IDA, any physical exertion leads to shortness of breath. Initially, most patients complain of increasing lethargy and fatigue. More unusual symptoms are headache, tinnitus and disturbance in taste. There is often a poor correlation between hemoglobin level and symptoms. As the severity of deficiency increases, the patients develop pallor of the conjunctiva, tongue, nailbeds and soft palate. In IDA of longer duration, there may be papillary atrophy of the tongue and, the nails may become spoon shaped (koilnychia). There may also be enlargement of the spleen (splenomegaly). In children, chronic IDA may lead to behavioral changes; they may have impairment of cognitive function and short attention spans and appear withdrawn.

13.3 Iron metabolism

Hemoglobin plays a crucial role in the transport of oxygen. With moderate IDA, there is a compensatory mechanism by biochemical changes to compensate for the reduced oxygen carrying capacity of blood. In contrast, in severe IDA, the markedly reduced hemoglobin content decreases the oxygen carrying capacity, leading to chronic tissue hypoxia.

Iron absorption

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