Anemia may be defined as a reduction in red blood cell (RBC) mass or blood hemoglobin concentration. The commonly used measures of anemia are hemoglobin and hematocrit. The hematocrit is the fractional volume of a whole blood sample occupied by RBCs. It is expressed as a percentage. Hemoglobin is a measure of the concentration of the RBC pigment hemoglobin in whole blood, expressed as grams per 100 mL (dL) of whole blood. Hemoglobin value is a direct measurement and is therefore more reliable than hematocrit, which is a calculated value. The overall clinical picture is important in the investigation for the causes of anemia. On the basis of the methods used to determine the normal range for hemoglobin and hematocrit values, it is expected that 2.5% of the healthy population will have apparently low hemoglobin and hematocrit, which may be incorrectly interpreted as anemia. On the other hand, hemoglobin and hematocrit values may be normal in a child with a chronic cardiac or pulmonary disorder, but below the level required to provide adequate tissue oxygenation, resulting in a functional anemia.
In general, there is considerable variation in hemoglobin and hematocrit values in pediatric patients. Therefore, it is important to use age- and sex-adjusted norms when evaluating a pediatric patient for anemia.
AGE-DEPENDENT VARIATION
Erythropoiesis is active during intrauterine life. The hemoglobin value at birth of a full term newborn (as seen in cord blood) is approximately 16.6 g/dL, and the lowest acceptable value is 13.8 g/dL (Table 54.1). The mean corpuscular volume (MCV) of RBCs is also increased in the newborn, so that values <96 μ3 indicate microcytosis. On exposure to increased oxygen after birth, RBC production decreases during the first few days, reaches a minimum during the second week, and subsequently rises to high values at approximately 3 months. This variation in erythropoiesis results in hemoglobin and hematocrit nadirs at 6 to 9 weeks of age (the lowest level is 9 g/dL in a full-term infant), called the physiologic anemia of infancy. Erythropoietin levels correspond with these findings, and in term infants these levels are lowest at 1 month and highest at 2 months of age. Anemia in preterm infants may be more pronounced because of inadequate iron stores and because of the shorter lifespan of preterm RBCs. The mean half-life of RBCs in term infants is approximately 23 days, as opposed to 17 days in preterm infants and up to 35 days in adults. The physiologic anemia in a preterm infant may therefore be seen sooner and last longer than observed in a full-term infant.
Infants with inherited RBC membrane abnormalities, such as hereditary spherocytosis, may present with exaggerated anemia in the neonatal period because of the concomitant decrease in erythropoiesis and the increase in splenic RBC destruction that occurs after birth.
During late infancy and childhood, the hemoglobin concentration progressively increases (Table 54.2). With the onset of puberty, differences between the hemoglobin concentration in the sexes become apparent; values for boys are higher by approximately 1 to 1.5 g/dL. African-American children may have hemoglobin levels lower than those of Asian or white children by approximately 0.5 g/dL.
CLASSIFICATION OF ANEMIA
Anemias are commonly classified on the basis of:
Morphology. The anemia is microcytic, normocytic, or macrocytic. The most reliable laboratory indicator of morphology is the MCV.
Physiology. The anemia is caused by either decreased production or increased loss or destruction of RBCs or both. The most reliable indicator of physiology is the reticulocyte count.
TABLE 54.1 CORD BLOOD VALUES
Mean
±2 SD
Hemoglobin
16 g/dL
13.8-20.0 g/dL
Mean corpuscular volume
106 μ3
96-116 μ3
Reticulocytes
4%
3%-7%
Values are compiled from various sources. SD, standard deviation.
It is important to use both systems of classification simultaneously as one proceeds with the investigation for the cause of anemia (Tables 54.3 and 54.4).
HISTORY AND PHYSICAL EXAMINATION
A thorough history and physical examination are critical in the investigation of anemia (Table 54.5).
History
The age and sex of the patient and the duration of the anemia/ symptoms are helpful in elucidating the etiology of anemia (Table 54.6). The most frequent causes of anemia in the newborn are hemolysis and blood loss. Primary nutritional iron deficiency anemia occurs more frequently during early toddlerhood and in adolescent girls. Clinical manifestations of the more common hemoglobinopathies are unusual in the neonatal period. The clinical manifestations of anemia (Tables 54.7 and 54.8) depend on age and duration of the anemia and include lethargy, tachycardia, and pallor. Anemic infants may present with irritability and poor oral intake. Patients with chronic anemia may be well compensated and may not have significant complaints. Cardiovascular decompensation is related to the acuity and the severity of the anemia, and neurologic changes become apparent only with the worsening of anemia.
Important historical clues signifying hemolytic episodes include change in urine color, scleral icterus, or jaundice.
TABLE 54.2 hEMOGLOBIN VALUES INDICATING ANEMIA IN DIFFERENT AGE GROUPS
Age
Hb (g/dL)
Infancy
2-3 Months
9.0 (Term)
8.5 (Low birth weight)
3-6 Months
9.5
6-12 Months
10.0
Childhood
12-24 Months
10.5
>24 Months
11.5
Adolescence
>13 Years
12.0 (Female)
13.5 (Male)
TABLE 54.3 MORPHOLOGIC CLASSIFICATION OF ANEMIA
Normocytic (normochromic): normal MCV
Aplastic (hypoplastic) anemia
Anemia secondary to bone marrow infiltration (i.e., leukemia, neuroblastoma)
Anemia of chronic disease (anemia of inflammation)
Rare anemias
Congenital absence of transferrin
Copper deficiency
Lymphoid hamartoma syndrome (Castleman disease)
Hemoglobin E
Macrocytic: increased MCV
Nutritional (primary or secondary): folic acid or B12 deficiency
Malabsorption syndromes
Juvenile pernicious anemia
Phenytoin therapy
Transcobalamin II deficiency
Congenital folic acid malabsorption
Congenital B12 malabsorption
Blind loop syndrome
Surgical resection
Hypothyroidism
Down syndrome
Drug-induced (chemotherapy)
Congenital dyserythropoietic anemias
Primary bone marrow disorders
Myeloproliferative disorders
Aplastic anemia (congenital or acquired)
Diamond-Blackfan anemia
Pearson syndrome
MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin.
A history of blood loss is essential and should include:
Gastrointestinal blood loss, which can manifest as any change in stool color or presence of blood in the stools.
Vaginal blood loss. Teenaged girls may have excessive menstrual loss, which is not evident to them; therefore, information regarding the menstrual history including duration of periods, flow, quantitation and saturation of tampons or pads, should be obtained.
Excessive nose bleeds.
Prior anemic episodes, duration, etiology, and resolution, as well as all prior therapy for anemia should be reviewed. A prior complete blood count (CBC) for comparison is helpful. In pediatrics, a frequently seen diagnostic error is when a patient with thalassemia trait is treated with iron supplements because of microcytic anemia. In addition to a complete past medical and surgical history, a careful review of symptoms should be made to elucidate chronic underlying infectious or inflammatory conditions that may result in anemia.
