Introduction
Background
Anemia refers to a hemoglobin or hematocrit level lower than the age-adjusted reference range for healthy children. In adolescents and adults, normal values vary according to sex. Racial differences are apparent, with black children having lower normal values than white and Asian children of the same age and socioeconomic background. With a statistical threshold set at 2 standard deviations lower than the mean for the healthy population, 2.5% of the healthy population is classified as anemic. Physiologically, anemia is a condition in which reduced hematocrit or hemoglobin levels leads to diminished oxygen-carrying capacity that does not optimally meet the metabolic demands of the body. These points must be considered when evaluating a child for possible anemia.
Anemia is not a specific disease entity but is a condition caused by various underlying pathologic processes. It may be acute or chronic. This article provides a general overview of anemia with an emphasis on the acute form. In addition, conditions are emphasized in which anemia is the only hematologic abnormality. The combination of anemia with leukopenia, neutropenia, or thrombocytopenia may suggest a more global failure of hematopoiesis caused by conditions such as aplastic anemia, Fanconi anemia, myelofibrosis, or leukemia; these diagnoses are considered in more detail in other eMedicine articles.
Pathophysiology
The main physiologic role of RBCs is to deliver oxygen to the tissues. Certain physiologic adjustments can occur in an individual with anemia to compensate for the lack of oxygen delivery. These include (1) increased cardiac output; (2) shunting of blood to vital organs; (3) increased 2,3-diphosphoglycerate (DPG) in the RBCs, which causes reduced oxygen affinity, shifting the oxygen dissociation curve to the right and thereby enhancing oxygen release to the tissues; and (4) increased erythropoietin to stimulate RBC production.
The clinical effects of anemia depend on its duration and severity. When anemia is acute, the body does not have enough time to make the necessary physiologic adjustments, and the symptoms are more likely to be pronounced and dramatic. In contrast, when anemia develops gradually, the body is able to adjust, ameliorating the symptoms relative to the degree of the anemia.
The underlying pathologic processes that cause anemia can be broadly categorized as (1) decreased or ineffective red cell production, (2) increased red cell destruction, or (3) blood loss.
Frequency
United States
Among all races, ages, and socioeconomic groups studied, an overall steady decline (from 7.8% in 1975 to 2.9% in 1985) in prevalence of anemia in the US pediatric population (aged 6 mo to 6 y) has been observed. Data show continued decline in the prevalence of anemia from the mid 1980s to the mid 1990s.1 Iron deficiency is the most common etiology.
International
In developing nations, the prevalence of anemia is extremely high. This is particularly true in preschool-aged children, in whom the prevalence reached as high as 90% of the sample population studied. Although iron deficiency is identified as the major factor, the etiology is often multifactorial, including recurrent or chronic infections (bacteria, parasites), malnutrition, and reduced immunity.
In addition, the prevalence of certain hereditary forms of anemia (eg, thalassemia, sickle cell disease) varies with ethnicity and, thus, with geography. For instance, α thalassemia, which may be the most common single gene disorder in the world, has a frequency of as much as 68% in the southwest Pacific, 20-30% in western Africa, and 5-10% in the Mediterranean region. β thalassemia mutations have high frequencies in the Mediterranean, northern Africa, southeast Asia, and India, but they have low frequencies in Great Britain, Iceland, and Japan.
Mortality/Morbidity
Mortality and morbidity rates vary according to the underlying pathologic process causing the anemia, the degree of severity, and the acuteness of the process. When a precipitous drop in the hemoglobin or hematocrit level occurs (eg, due to massive bleeding or acute hemolysis), the clinical presentation is typically dramatic and can be fatal if the person is not immediately treated. In addition to the signs and symptoms of anemia, patients can present with congestive heart failure (CHF) or hypovolemia. Cerebral injury has been reported in perioperative patients with anemia.2
Race
Acute anemia is universal, but the likely underlying etiologies are influenced by race. Inherited red cell disorders are predominant in certain racial populations, such as sickle cell disease in black persons, β thalassemia in persons of Mediterranean ethnicity, and α thalassemia in Asians, African Americans, and others.
Sex
Sex predisposition to anemia varies according to the underlying etiology. For instance, certain hereditary X-linked red cell disorders (eg, G-6-PD deficiency) are observed in males. Anemia caused by blood loss can be observed in males with an X-linked bleeding disorder (eg, hemophilia). Females with the autosomally inherited von Willebrand disease may be anemic because of heavy blood loss during menstruation. Acquired hemolytic anemia related to autoimmune disorders such as systemic lupus erythematosus is more common in females because of their relative predisposition to autoimmune disease.
Age
The newborn period is one age group in which acute anemia most commonly occurs. Significant blood loss can occur from birth trauma or blood exchange from the baby's mother or the placenta. Isoimmune anemia can result from maternal antibodies crossing the placenta. Neonates have a shorter red cell life span and limited erythropoiesis that can aggravate any hemolytic process. Abnormalities of fetal hemoglobin may cause anemia that resolves with the normal shift to adult-type hemoglobins.
Nutritional anemia is common in infancy because of the associated rapid growth (necessitating an increase in red blood cell mass) and dietary adjustments.
With exposure to new infections in early childhood, the anemia of acute infection is common. Rarely, severe autoimmune hemolytic anemia can be triggered by certain infections.
Adolescence is characterized by rapid growth and vulnerability to nutritional anemia. In addition, blood loss with heavy menstruation can be observed in adolescent girls.
Clinical
History
History of the individual with anemia must include data that demonstrate the acuteness and severity of the condition and suggest a cause of the anemia.
- Symptoms of anemia include pallor, fatigue, lethargy, dizziness, and anorexia.
- Jaundice and, occasionally, dark urine may be present with significant hemolysis.
- Failure to thrive indicates a long-standing condition. It may reflect the anemia itself or the underlying cause (eg, chronic renal failure).
- Patients with acute anemia are overtly symptomatic when the condition is severe, whereas those with chronic anemia may go undiagnosed because they are asymptomatic relative to the degree of anemia.
- Age is an important clue to the etiology of the anemia. For example, blood loss, isoimmunization, and congenital red cell disorders are common causes of anemia in newborns. Although observed in older infants, toddlers, and adolescent girls, iron deficiency anemia is unlikely in newborns or infants in whom iron stores from the mother are usually adequate and in prepubertal school-aged children in whom no rapid growth and expansion of blood volume occurs.
- Some hereditary X-linked disorders are observed mainly in males. A common example is acute hemolysis in G-6-PD deficiency.
- Knowing the racial background or ethnicity can help diagnose inherited abnormalities of hemoglobin production. Examples include the following:
- Thalassemias, hemoglobin S and C in the black population
- β thalassemia in individuals of Mediterranean descent
- α thalassemia and hemoglobin E disease in Asian individuals
- Red cell enzyme defects (eg, G-6-PD deficiency) among individuals from the Mediterranean, Africa, and southeast Asia
- Review dietary history, including milk intake in infants and toddlers and the sources of other nutrients (eg, iron, folate, vitamin B-12).
- Note details about sources of blood loss, recent infections, travel, drug exposures, chemicals (eg, lead), toxins, and oxidants.
- Inquire about symptoms of hypothyroidism (eg, cold intolerance, constipation, lethargy, poor growth).
- Inquire regarding a neonatal history of anemia, jaundice, phototherapy, transfusion, any other chronic medical illnesses or complaints, and medications.
- When reviewing the family history, include questions regarding anemia, jaundice, gallbladder surgery, splenomegaly or splenectomy, autoimmune diseases, or a bleeding disorder.
Physical
- Check vital signs.
- Patients with acute and severe anemia appear in distress with tachycardia, tachypnea, and hypovolemia.
- Patients with chronic anemia are typically well compensated and only have tachycardia.
- To evaluate chronicity, plot growth parameters, which may affect the urgency of treatment.
- Note pallor, jaundice, edema, and signs of bleeding (eg, petechiae, bruising).
- Patients with significant anemia often have a systolic ejection murmur.
- Look for signs of congestive heart failure (CHF), such as tachycardia, gallop rhythm, tachypnea, cardiomegaly, hepatomegaly.
- Splenomegaly can be found in many hemolytic anemias or may reflect infiltration in malignancy. In young patients with sickle cell disease, splenic sequestration can manifest with tender splenomegaly and an exacerbation of anemia. Passive congestion of the spleen may complicate CHF.
- Note any dysmorphic features and other congenital anomalies.
- Facial bony prominences (eg, frontal bossing) are signs of extramedullary hematopoiesis associated with chronic severe hemolytic anemias and thalassemias.
- Some congenital bone marrow failure syndromes (eg, Diamond-Blackfan anemia and Fanconi anemia) are associated with facial, limb, and other anomalies.
- Signs of hypothyroidism include low body temperature, failure to thrive, dry skin, and thinning of the hair.
Causes
Causes of anemia are either inherent in the RBCs or related to an external factor. As noted above, these can be simplified into 3 main categories, although more than one mechanism may be involved in some anemias.
- Anemia caused by decreased red cell production (generally develops gradually and causes chronic anemia)
- Marrow failure
- Diamond-Blackfan anemia (congenital pure red cell aplasia)
- Transient erythroblastopenia of childhood
- Aplastic crisis caused by parvovirus B19 infection (in patients with an underlying chronic hemolytic anemia)
- Marrow replacement (eg, malignancies, myelofibrosis, osteopetrosis)
- Impaired erythropoietin production
- Anemia of chronic disease in renal failure
- Chronic inflammatory diseases
- Hypothyroidism
- Severe protein malnutrition
- Defect in red cell maturation and ineffective erythropoiesis
- Nutritional anemia secondary to iron, folate, or vitamin B-12 deficiency
- Congenital dyserythropoietic anemia
- Sideroblastic anemias
- Thalassemias
- Erythropoietic protoporphyria
- Myelodysplastic syndromes3
- Marrow failure
- Anemia caused by increased red cell destruction (hemolysis)
- Extracellular causes
- Mechanical injury (hemolytic-uremic syndrome, cardiac valvular defects)
- Antibodies (autoimmune hemolytic anemia)
- Infections, drugs, toxins
- Thermal injury to RBCs (with severe burns)
- Intracellular causes
- Red cell membrane defects (eg, hereditary spherocytosis, elliptocytosis)
- Enzyme defects (eg, G-6-PD deficiency, pyruvate kinase deficiency)
- Hemoglobinopathies (sickle cell disease, unstable hemoglobinopathies)
- Paroxysmal nocturnal hemoglobinuria
- Extracellular causes
- Anemia caused by blood loss
- Obvious or occult site of blood loss: GI tract, intra-abdominal, pulmonary, intracranial (in neonates)
- Particular risk of massive hemorrhage (internal or external) for patients with bleeding disorders
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References
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Further Reading
Keywords
anemia, low hemoglobin, low hematocrit, anemic, reduced red cell mass, diminished oxygen-carrying capacity, hematologic abnormality, decreased or ineffective red cell production, increased red cell destruction, blood loss, acute anemia, congestive heart failure, CHF, hemolysis, hemorrhage, thalassemia, splenectomy, Fanconi anemia, aplastic anemia, treatment, diagnosis, myelofibrosis, leukemia, sickle cell disease, systemic lupus erythematosus, chronic renal failure, iron deficiency anemia, X-linked disorders, tachycardia, gallop rhythm, tachypnea, cardiomegaly, hepatomegaly, Diamond-Blackfan anemia, transient erythroblastopenia of childhood, hypothyroidism, pyruvate kinase deficiency
