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| REVIEW ARTICLE |
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| Year : 2020 | Volume
: 9
| Issue : 3 | Page : 91-95 |
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Pediatric anemia – Profile in the Indian subcontinent
A Sivakami, Bageshree Seth
Department of Pediatrics, MGM Hospital and Medical College, Kamothe, Navi Mumbai, Maharashtra, India
| Date of Submission | 01-Nov-2020 |
| Date of Decision | 12-Dec-2020 |
| Date of Acceptance | 02-Jan-2021 |
| Date of Web Publication | 30-Jun-2021 |
Correspondence Address:
Dr. Bageshree Seth
Department of Pediatrics, MGM Hospital and Medical College, Kamothe, Navi Mumbai, Maharashtra
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jpai.jpai_12_20
Anemia is a condition in which the number of red blood cells, and consequently, their oxygen-carrying capacity is insufficient to meet the body's physiologic needs. The mean hemoglobin level at the time of delivery in full-term normal infants is 16.5 ± 3 gm% in cord blood. After rising in the first 24 h, it then starts falling progressively to reach a nadir of 12.0 ± 1 gm% by 1 year of age. Anemia is one of the leading causes of mortality and morbidity in under-five children, as high incidence has been noted among them. Early screening, diagnosis, and interventions are helpful to prevent the consequences associated with it. Nutritional anemia was diagnosed as the most common cause of anemia in the Indian subcontinent. It is common in infancy and in female children. Malnutrition and splenomegaly were common signs in anemic children. There are wide variations in etiology and clinical features in hospitalized children depending on various factors.
Keywords: Anemia, hemoglobin level introduction, pediatric anemia
How to cite this article:
Sivakami A, Seth B. Pediatric anemia – Profile in the Indian subcontinent. J Pediatr Assoc India 2020;9:91-5 |
| Introduction | |  |
Anemia is a condition in which the number of red blood cells (RBCs), and consequently, their oxygen-carrying capacity is insufficient to meet the body's physiologic needs. Anemia can be alternatively defined as a hemoglobin level in the blood that is below the lower extreme of the normal range for the age and sex of the individual.[1] The hemoglobin level is therefore the prime determinant in the diagnosis of anemia. The mean hemoglobin level at the time of delivery in full-term normal infants is 16.5 ± 3 gm% in cord blood. After rising in the first 24 h, it then starts falling progressively to reach a nadir of 12.0 ± 1 gm% by 1 year of age.[2],[3] The hemoglobin level then rises till the beginning of puberty. The adult values for females are established at puberty, while in males, it rises further and reaches adult values which are 1.5 g% higher than females due to effect of androgens. Iron deficiency is thought to be the most common cause of anemia globally, but other nutritional deficiencies (including folate, vitamin B12, and Vitamin A), acute and chronic inflammation, parasitic infections, and inherited or acquired disorders that affect hemoglobin synthesis, RBC production, or RBC survival, can all cause anemia.[4],[5]
| World Health Organization Grading of Anemia | | |
The cutoffs defining mild, moderate, and severe anemia were first presented in the 1989 guide “Preventing and controlling anaemia through primary health care”[1] and then modified for pregnant women, nonpregnant women, and children <5 years of age in “The management of nutrition in major emergencies.”[2] The overall anemia cutoffs have been unchanged since 1968, with the exception that the original age group of children 5–14 years of age was split, and a cutoff of 5 g/l lower was applied to children 5–11 years of age to reflect findings among noniron deficient children in the USA.[6] Although these cutoffs were first published in the late 1960s, they have been included in numerous subsequent World Health Organization publications[7],[8] and were additionally validated by findings among participants in the Second National Health and Nutrition Examination Survey II who were unlikely to have iron deficiency based on a number of additional biochemical tests.[9] The [Table 1] below shows the cutoff value of hemoglobin to differentiate into mild, moderate, and severe anemia in various age groups.
Classification of anemia
Anemias can be classified in several ways. Two of the most widely accepted ways of classifying anemia are based on pathophysiology and morphology.[10],[11]
Pathophysiological classification divides anemias into three groups
- Anemia due to increased blood loss
- Anemia due to impaired red cell production
- Anemia due to increased red cell destruction.
Morphologically, anemias are classified based on red cell size, hemoglobin content, and red cell indices as follows
- Microcytic, hypochromic anemia
- Normocytic, normochromic anemia
- Macrocytic anemia.
| Pathophysiological Classification | | |
Anemia of blood loss
This can occur due to acute and massive blood loss, for example, trauma or menorrhagia. Usually, massive blood loss results in normochromic and normocytic anemia. However, when the blood loss is slow and insidious, for example, occult gastrointestinal (GI) blood loss, the effects of anemia appear when the rate of loss is more than the rate of production and there is depletion of iron stores. In these cases, anemia may be hypochromic and microcytic morphologically.
Anemia due to impaired red cell production
Impaired red cell production may occur due to the following mechanisms:
- Cytoplasmic maturation defects due to deficient heme synthesis (iron-deficiency anemia) or deficient globin synthesis (Thalassemia syndromes)
- Nuclear maturation defects due to Vitamin B12 and/or folic acid deficiency (megaloblastic anemia)
- Defect in stem cell proliferation and differentiation as in aplastic anemia or pure red cell aplasia
- Anemia of chronic disorders such as infection, inflammatory disorders, and connective tissue disorders
- Bone marrow infiltration due to leukemia, lymphoma, and myeloproliferative disorders.
Anemia due to increased red cell destruction
These anemias are conventionally called hemolytic anemias. Hemolysis of red cells could occur due to extracorpuscular or extrinsic red cell abnormalities and intracorpuscular or intrinsic red cell abnormalities. The red cell lifespan is shortened in hemolytic anemias which, if compensated by increased red cell turnover from the bone marrow, does not result in anemia. These anemias are therefore episodic in nature. Jaundice is usually an accompanying symptom of hemolytic anemia.
| Morphological Classification | | |
There are three main types of anemia recognized on the basis of mean corpuscular volume, mean corpuscular hemoglobin, and MCH concentration (MCV, MCH, and MCHC) of the red cells.
Microcytic, hypochromic anemia
The MCV is low (<80 fl) and MCH and MCHC are also low (<27 pg, <30 g/dl). The red cells correspondingly appear microcytic and hypochromic on the peripheral blood smear. The most common examples are iron-deficiency anemia, thalassemia, and sideroblastic anemia.
Normocytic, normochromic anemia
The MCV, MCH, and MCHC are in the normal range. The red cells appear normal in size and hemoglobin content on the blood smear. The common examples of normocytic normochromic anemia are anemia due to blood loss, hemolytic anemias, anemia due to bone marrow failure, bone marrow infiltration , anemia of chronic infection or inflammation.
Macrocytic anemia
The MCV is high (>96 fl), which manifests as macrocytic or large red cells on the peripheral smear. The red cells are usually normochromic. The common examples of macrocytic anemia are anemia due to vitamin B12 and folate deficiency causing megaloblastosis of the marrow. Sometimes, increased reticulocytes due to hemolytic anemia can also cause macrocytosis as reticulocytes are larger than mature RBCs.
| Reticulocyte Count | | |
The reticulocyte count will help to differentiate the underlying physiological process causing anemia. The normal reticulocyte count in children is 1% of total RBCs, with an absolute reticulocyte count of 25,000–75,000/mm3. In case of anemia due to ineffective erythropoiesis or marrow failure, the reticulocyte count will be low or normal, whereas it is increased in case of destruction or loss of RBCs due to hemolysis/sequestration or bleeding.
The various causes of anemia in the pediatric age can be grouped as follows:
Microcytic anemia with low/normal retic count
- Iron-deficiency anemia
- Thalassemia trait
- Chronic disease/inflammation
- Lead poisoning
- Sideroblastic anemia
- Copper deficiency
- Iron refractory iron-deficiency anemia.
Microcytic anemia with high retic count
- Thalassemia syndromes
- Hemoglobin C and E syndromes
- Pyropoikilocytosis.
Normocytic with low/inadequate retic count
- Chronic disease/inflammation
- RBC aplasia (Infection, drugs)
- Malignancy
- Endocrinopathies
- Renal failure
- Acute bleeding
- Hypersplenism
- Dyserythropoietic anemia II
- Hemophagocytic syndrome.
Normocytic anemia with high retic count
- Antibody-mediated hemolysis
- Hypersplenism
- Microangiopathy (hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulation)
- Membranopathies (spherocytosis, elliptocytosis, and ovalocytosis)
- Enzymopathies (Glucose-6 – phosphate dehydrogenase deficiency and Pyruvate Kinase deficiency deficiencies)
- Hemoglobinopathies (HBSS and SC).
Macrocytic anemia with low/inadequate retic count
- Folate deficiency
- Vitamin B12 deficiency
- Acquired aplastic anemia
- Congenital aplastic anemia (Diamond–Blackfan, Fanconi, and Pearson syndrome)
- Drug induced
- Trisomy 21
- Hypothyroidism
- Orotic aciduria.
Macrocytic anemia with high retic count
- Dyserythropoeitic anemia I, III
- Active hemolysis with elevated retic count.
| Clinical Features of Anemia | | |
The symptoms and signs in an anemic patient are due to anemia itself or clinical manifestation of the underlying disorder causing anemia. It varies from one person to another depending upon the degree of anemia and the severity of the underlying pathology. The symptoms of anemia pertaining to hemoglobin level depend on the rate of development of anemia as well as the age and cardiovascular state of the patient.
Symptoms
Tiredness, lethargy, easy fatiguability, and generalized muscular weakness are the common and earliest symptoms of anemia. These symptoms are not specific to anemia but can be seen in other disorders too. Other symptoms include unusually rapid heart rate and shortness of breath with strenuous exercise, difficulty in concentration, headache, dizziness, pale skin, leg cramps, and insomnia.
In children where anemia is due to iron deficiency, in addition to these, they also might have a hunger for strange substances such as paper, ice or dirt (pica), angular cheilitis, and platynychia or koilonychia.
Children with anemia due to Vitamin B12 deficiency may have symptoms like paresthesia, hallucinations, paranoia and delirium. Infants have symptoms such as excessive crying, irritability, and failure to gain weight and poor oral intake. Other symptoms include overt signs of blood loss like hematuria or melena.
The identification of cause of anemia is important so that appropriate therapy is used to treat anemia. Therefore, it is important to know the various clinical symptoms with which a child can present and also a detailed medical history and physical examination has to be done.[12],[13],[14]
Relevant medical history that should be asked for in those patients suspected to have anemia in addition to the above-mentioned symptoms includes:
- As occult bleeding from GI tract is an important cause of anemia, one should be asked for symptoms such as abdominal pain, altered bowel habits, abdominal distention, or diarrhea. In addition to this, obvious bleeding history such as hematemesis, epistaxis, and menorrhagia should also be elicited
- Any bleeding tendencies due to trivial trauma or easy bruising suggest that anemia is due to a disorder causing thrombocytopenia, a coagulation defect, or to renal insufficiency
- Bone pains may occur in anemia due to marrow infiltration or replacement, such as acute leukemia, lymphoma, and myelofibrosis
- History of any recurrent blood transfusions in the family, history of sibling death, or any blood disorders in the family pertains to some inherited cause of severe anemia. It is also important to ask for any history of recent drug intake as well as exposure to environmental pollutants, as anemia can also occur due to hemolysis, lead poisoning, etc.
On physical examination, the various signs that can be noted are skin pallor, icterus (in case of hemolytic anemia), frontal and parietal bossing, delayed closure of anterior fontanelle, hyperpigmentation, and knuckle pigmentation may be noticed. Associated thumb and limb anomalies can also be noted.
Other findings noted on physical examination include hepatosplenomegaly, cardiovascular abnormalities suggestive of congestive cardiac failure like tachycardia, gallop rhythm, bounding pulse, neurological changes, and malnutrition on anthropometry.
After recognition of an anemic patient, type and cause of anemia can be confirmed by examination of various blood parameters: The type of anemia is generally indicated by the features of the red cells, leukocytes, and platelets noted in the examination of the blood. It is important to observe the level of hemoglobin, red cell count, mean red cell volume, MCH, MCHC, leukocyte count, and platelet count. Examination of the peripheral blood smear plays a key role in establishing the cause of anemia, as it remains the best method for detecting aberrations in red cells indicative of specific pathological entities, and of associated abnormalities in leukocytes. In appropriate circumstances, these tests are supplemented by the determination of erythrocyte sedimentation rate and the reticulocyte count. The information obtained by such investigations can serve in turn as the basis for further, more specialized, tests for establishing the nature of the particular pathological process responsible for the anemia.
Anemia is recognized mainly on the basis of red cell indices which include:
- MCV: It provides a reliable index of the average size of red cells. A subnormal value (< approx. 80 fl) is indicative of microcytosis and an elevated level (>96 fl) is indicative of macrocytosis
- MCH: It is the mean amount of hemoglobin per red cell. A subnormal MCH (<27 pg) occurs in microcytosis but is even lower when microcytosis occurs in conjunction with a subnormal concentration of hemoglobin in the red cell, as in thalassemia minor or iron deficiency
- MCHC: A subnormal MCHC (<30 g/dl) is usually indicative of an abnormality where interference with the synthesis of hemoglobin is greater than that of other constituents of the red cells, as in thalassemia or iron-deficiency anemia. Elevated values reflect dehydration of the erythrocyte, and one of the relatively few important clinical causes of this phenomenon is spherocytosis.
After concluding the morphological type of anemia whether microcytic, macrocytic, or normocytic, the specific diagnosis can be made by performing various other investigations like iron studies, VitB12 level, RBC folate levels, G6PD, red cell enzyme studies, high-performance liquid chromatography, and bone marrow aspiration/biopsy.[15],[16],[17]
| Studies in Subcontinent | | |
In a study conducted by Janjale et al. at a medical college in Nasik, 59 patients with severe anemia, age ranging from 6 months to 12 years, were enrolled. Fifty percent of the patients were below 3.5 year old with males accounting for 60%. Nearly 40% of patients had Grade — malnutrition. Nutritional anemia was diagnosed as the etiology in 56% of cases. Only 6% of cases had hemolytic anemia (thalassemia and sickle cell disease), 5% were acute lymphocytic leukemia, and 5% had malaria. None of the patients had B12 deficiency as serum B12 levels were not done in the study population. About 47.46% of patients had microcytic anemia, while 39% had normocytic anemia. Nearly 22.03% of patients presented with respiratory infections, fever being a presenting feature in 66% of patients. Sahana KS et al. studied anemia in hospitalized infants at a tertiary care hospital. Fifty-six percent of infants between 6 and 12 months of age were anemic, the mean age being 9.6 months and 81% being females. Sixty-six percent were admitted for respiratory infections, 17% had GI infections. A history of prematurity was obtained in 34.7% of infants, while 40% were low birth weight. Fifty-one percent of cases were found to have improper weaning technique. Nonvegetarian diet was included in the feeds in 4%–5% of infants before 1 year of age. Thirty-nine percent infants had various grades of malnutrition, 7% had Grade 3 Protein energy malnutrition, while none were Grade 4. Severe anemia was found in only 3% of cases. About 69.4% of cases were microcytic hypochromic anemia. The study concluded that improper weaning techniques, prematurity, and low birth weight were important risk factors for moderate and severe anemia in infants.[3],[18]
In a study done by Firdos Saba et al. at a muti specialty hospital in Bangalore, the prevalence of anemia was 72.79%, the most common cause being nonhemoglobinopathy in 98% of children. Microcytic hypochromic anemia was the most common type of morphological anemia in 48% of patients. In a study done at Dehradun by Chhabra et al. to find the etiology of anemia in hospitalized children, 118 children between 6 months to 14 years of age were studied. Nearly 64.4% were boys. About 54.2% of cases had severe anemia. Fifty-five percent had irondeficiency anemia, while 9.3% had megaloblastic anemia. Sixteen percent of cases were due to malignancies. Fifty-one percent of patients were malnourished. About 37.2% had splenomegaly. Pancytopenia was present in 11% of cases. Macrocytic anemia and pancytopenia were more common in the older age group of 11–14 years.[19],[20]
A Chennai study by Antony Jenifer et al. in children aged 1 month to 14 years of age studied admitted patients with severe anemia to find the etiology. Iron-deficiency anemia was the most common cause in 40% of cases. Other causes were malaria (17%), sickle cell anemia (15%), beta-thalassemia (11%), and malignancies in 4%. Madoori et al. studied the clinicohematological profile and outcome of anemia in children at a tertiary care center at Telangana, it being a retrospective study. Three hundred sixteen cases of anemia aged 2 months to 14 years were reviewed, 55% being males. Fifty-eight percent cases were attributed to iron-deficiency anemia, 27% to sickle cell anemia, 9% to thalassemia, while only 5% had megaloblastic anemia. Fever was a presenting feature in 57% of patients, splenomegaly was found in 30%, and only 2.85% had bleeding manifestations.[21],[22]
Eight hundred forty-one anemic children with nutritional anemia aged 6 months to 12 years were studied by Bhatti et al. in Pakistan. Nearly 7.3% of patients had severe nutritional anemia. The factors attributed to nutritional anemia were poverty, inadequate diet, and malnutrition. Fifty-eight percent of children had an inadequate diet with poor caloric intake; wasting and stunting was detected in 56%–60% of cases. Iron deficiency was the most common etiology accounting for 73% in children upto 5 years of age, while older children mainly had megaloblastic anemia (57%).[23]
| Conclusion | | |
Anemia is one of the leading causes of mortality and morbidity in under-five children, as high incidence has been noted among them. Early screening, diagnosis, and intervention are helpful to prevent the consequences associated with it.
Author's contribution
SA was responsible for literature search and initial manuscript. BS conceptualized and did the final drafting of the paper. Overall guidance and expert opinion was given by BS.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 3. | Janjale A, Pande S, Sonawane R, Ahire N, Sonawane S. A study of severe anemia in children in a tertiary care institute. MVP J Med Sci 2018;5:33-8. |
| 4. | Saba F, Poornima S, Balaji PA, Varne SR, Jayashree K. Anemia among hospitalized children at a multispeciality hospital , banglore (karnataka), India. J Fam Med Prim Care 2014;3:48-53. |
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| 7. | The Management of Nutrition in Major Emergencies. Geneva: World Health Organization; 2000. |
| 8. | Nutritional Anaemias. Report of a WHO Scientific Group. Geneva: World Health Organization; 1968. |
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| 11. | Muoneke VU, ChidiIbekwe R. Prevalence and aetiology of severe anaemia in under-5 children in abakaliki South Eastern Nigeria. Pediatr Therapeut 2011;1:107. |
| 12. | Mghanga FP, Genge CL, Yeyeye L, Twalib Z, Kibopile W, Rutalemba F, et al. Magnitude, severity, and morphological types of anemia in hospitalized children under the age of five in Southern Tanzania. Cureus 2017;9:E1499. |
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| 19. | Saba F, Poornima S, Balaji PA, Varne SR, Jayashree K. Anemia among hospitalized children at a multispeciality hospital, banglore (karnataka), India. J Fam Med Prim Care 2014;3:48-53. |
| 20. | Chhabra A, Chandar V, Gupta A, Chandra H. Megaloblastic anaemia in hospitalised children. J Indian Acad Clin Med 2012;13:195-7. |
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| 22. | Madoori S, Ramya C, Valugula S, Kotla S. Clinico hematological profile and outcome of anemia in children at tertiary care hospital, Karimnagar, Telangana, India. Int J Res Med Sci 2015;3:3567-71. |
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[Table 1]
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