Pediatric Acute Anemia 

Updated: Aug 22, 2017
Author: Susumu Inoue, MD; Chief Editor: Robert J Arceci, MD, PhD 

Overview

Practice Essentials

Pediatric anemia refers to a hemoglobin or hematocrit level lower than the age-adjusted reference range for healthy children. Physiologically, anemia is a condition in which reduced hematocrit or hemoglobin levels lead to diminished oxygen-carrying capacity that does not optimally meet the metabolic demands of the body. (See Etiology.)

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, or may suggest a rapid destruction or trapping of all blood elements, such as hypersplenism, localized coagulopathy in a large hemangioma, or hemophagoctic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). (See Etiology.)

The main physiologic role of red blood cells (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, using all 4 mechanisms mentioned above (1, 3, and 4 in most cases), ameliorating the symptoms relative to the degree of the anemia. (See History and Physical Examination.)

Please see the following for more information:

  • Anemia

  • Emergent Management of Acute Anemia

  • Pediatric Chronic Anemia

Complications

Acute and severe anemia can result in cardiovascular compromise. Moreover, if individuals with acute anemia are not treated immediately and appropriately, the resulting hypoxemia and hypovolemia can lead to brain damage, multiorgan failure, and death. Long-standing anemia can result in failure to thrive. (See Prognosis.)

Many studies have shown the deleterious effects of iron deficiency anemia or iron deficiency without anemia on the neurocognitive and behavioral development in children. Other complications can include congestive heart failure, hypoxia, hypovolemia, shock, seizure, and acute silent cerebral ischemic event (ASCIE; see Magnetic resonance imaging in research settings in Workup).[1]

Workup

To evaluate anemia, obtain initial laboratory tests, including the complete blood count (CBC), reticulocyte count, and review of the peripheral smear.

Chest radiography is performed in patients who may have congestive heart failure (CHF) and to rule out mediastinal mass (associated with acute leukemia).

Abdominal ultrasonography is used to assess for gallstones or splenomegaly in hemolytic anemia, while computed tomography (CT) scanning is used to evaluate occult bleeding in blunt trauma (eg, splenic rupture, subcapsular hemorrhage of the liver) or a bleeding disorder. Abdominal Doppler study is used to detect portal vein thrombosis.

Management

Transfusion with packed red blood cells (PRBCs) is the universal treatment for most individuals with severe acute anemia. The indication to transfuse should not be based solely on the hemoglobin or hematocrit levels; more importantly, one must consider the clinical effects or the signs and symptoms of the individual with anemia.[2]

Patient education

Girls with heavy and/or prolonged menstrual periods should seek medical attention (should tell parents to obtain CBC count). One of the most common reasons for fainting spell or syncope in adolescent girls is rapidly developing anemia due to menstrual blood loss.

Toddlers who drink more than 24 oz of milk a day most likely have iron deficiency. Primary care physicians should inquire about the amount of milk intake.[3]

Children diagnosed with anemia should be taught to look at their stool color and to report to their parents if it is tarry or bloody.

Educate the patient and/or the family about the specific disease that causes the anemia. For example, provide a list of drugs, food, and other agents to avoid because of their effect of triggering acute hemolysis in glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

In pediatrics beyond the immediate neonatal period, acute anemia is rare in otherwise healthy children. In most instances, it is due to blood loss, usually through the GI tract or via a heavy menstrual period. The most common reason for hospitalization because of acute anemia is so-called aplastic crisis in children with chronic hemolytic anemia who otherwise had been stable. The most common varieties are hereditary spherocytosis and sickle cell disease. Therefore, it would be prudent to educate parents regarding this complication, at the time when the diagnosis is established.

Etiology

Causes of anemia are either inherent in the RBCs or related to an external factor. The underlying pathologic processes that cause anemia can be broadly categorized as (1) decreased or ineffective red cell production, (2) increased red cell destruction (hemolysis), and (3) blood loss, although more than 1 mechanism may be involved in some anemias.

Anemia caused by decreased red cell production

This generally develops gradually and causes chronic anemia. Marrow failure may result from the following:

  • 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, leukemia, neuroblastoma, medulloblastoma, retinoblastoma, Ewing sarcoma, soft tissue sarcoma, myelofibrosis, osteopetrosis)

  • Aplastic anemia

  • Paroxysmal nocturnal hemoglobinuria (PNH)

Impaired erythropoietin production may result from the following:

  • Anemia of chronic disease in renal failure

  • Chronic inflammatory diseases

  • Hypothyroidism

  • Severe protein malnutrition

Defect in red cell maturation and ineffective erythropoiesis may result from the following:

  • Nutritional anemia secondary to iron, folate, or vitamin B-12 deficiency

  • Congenital dyserythropoietic anemia

  • Sideroblastic anemias

  • Thalassemias

  • Erythropoietic protoporphyria

  • Myelodysplastic syndromes[4]

Anemia caused by increased red cell destruction

Extracellular causes may include the following:

  • Mechanical injury (hemolytic-uremic syndrome, cardiac valvular defects, Kasabach-Merritt phenomenon or hemangioma with thrombocytopenia)

  • Antibodies (autoimmune hemolytic anemia)

  • Infections, drugs, toxins

  • Thermal injury to RBCs (with severe burns)

Intracellular causes may include the following:

  • Red cell membrane defects (eg, hereditary spherocytosis, elliptocytosis)

  • Enzyme defects (eg, G-6-PD deficiency, pyruvate kinase deficiency)

  • Hemoglobinopathies (sickle cell disease, unstable hemoglobinopathies)

  • PNH

Anemia caused by blood loss

Obvious or occult sites of blood loss may include the GI tract or intra-abdominal, pulmonary, or intracranial (in neonates) sites. Patients with bleeding disorders are at particular risk for massive hemorrhage (internal or external).

Acute anemia caused by multiple mechanisms

Anemia associated with acute infection is common. This may be mediated by increased destruction by erythrophagocytosis[5] and suppression of erythropoiesis by the infection.

Epidemiology

In adolescents and adults, normal values for the hemoglobin and hematocrit levels vary according to sex. Racial differences are also apparent, with black children having lower normal values than white and Asian children of the same age and socioeconomic background.

Occurrence

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 showed continued decline in the prevalence of anemia from the mid-1980s to the mid-1990s.[6] Iron deficiency was the most common etiology.

A prevalence study of anemia on selected groups using the National Health and Nutrition Examination Surveys covering 1988-1994 and 1999-2002 showed a decrease in the prevalence of anemia from 8% to 3.6% in children aged 12-59 months and from 10.8% to 6.9% in women aged 20-49 years. However, no significant change in the prevalence of iron deficiency anemia was seen in either group.[7]

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. Beta 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.

A study by Mujica-Coopman et al of anemia rates in children under age 6 years in Latin America and the Caribbean found the lowest rates in Chile (4.0%), Costa Rica (4.0%), Argentina (7.6%), and Mexico (19.9%). Anemia was found to pose a severe public health threat in Guatemala, Haiti, and Bolivia.[8]

A study by Aladjidi et al estimated that in the Aquitaine region of France, the incidence of the rare disease autoimmune hemolytic anemia in persons under age 18 years is 0.81 per 100,000 per year.[9]

Racial-related demographics

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.[10]

Sex-related demographics

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. Even without this disorder, they have a high risk of developing iron deficiency and iron deficiency anemia, quite often worsened by acute blood loss. 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-related differences in incidence

Acute anemia most commonly occurs among newborns. Significant blood loss can occur from birth trauma or blood exchange from the baby's mother (feto-maternal transfusion) 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. Deletion of α globin gene, unlike β globin gene mutation, causes anemia in neonates. Hemoglobin H disease is a good example (in neonates Hb Barts is the abnormal hemoglobin rather than Hb H).

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.

Prognosis

The prognosis depends on the severity and acuteness with which the anemia develops and the underlying cause of the anemia.

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.[11]

 

Presentation

History

The acute development of anemia in the pediatric age group commonly occurs in 2 situations, (1) acute blood loss and (2) acute hemolysis.

Acute blood loss

In neonates, blood loss can occur through the placenta, abruption, placenta previa, and fetomaternal transfusion. The former 2 can be known by history, while fetomaternal transfusion cannot be discerned from history findings. Iatrogenic blood loss through multiple blood samplings in extremely low birth weight infants can cause anemia rapidly.

In older children, the GI tract is the most common site of blood loss; common causes include esophageal and gastric varices (inquire about a history of umbilical vein catheterization during neonatal ICU stay), ulcerative colitis, and Crohn disease. Menstruating girls’ blood loss due to dysmenorrhea is an extremely common cause of acute blood loss (may or may not be associated with von Willebrand disease; ask about easy bruisability, frequent epistaxis, and family history of similar bleeding history).

A history of trauma is important (eg, rupture of spleen)

Rapid hemolysis

When taking the history, keep the following factors in mind:

  • Isoimmune or alloimmune hemolytic anemia (ABO incompatibility or Rh incompatibility in neonates) – (1) Mother’s blood group (ABO) and type (Rh); (2) minor Rh antigen incompatibility such as c, E, may cause severe hemolytic anemia (even if there is no ABO or D incompatibility), therefore do direct antiglobulin test (DAT) whenever there is a suspicion

  • Autoimmune hemolytic anemia – (1) History of a viral infection such as mycoplasma or Ebstein-Barr virus (EBV) may precede paroxysmal cold hemoglobinuria; (2) an infection with Streptococcuspneumoniae may cause autoimmune hemolytic anemia due to exposure of cryptic T antigen on the red blood cells by the bacterial neuraminidase

  • Transfusion reaction due to major blood group incompatibility - Usually due to clerical error or misidentification of patient delayed transfusion reaction due to previously unrecognized antibodies to red blood cell antigens (may occur a few days to 1 wk after previous transfusion)

  • Ingestion of strong oxidants in a child with G-6-PD deficiency - Ingestion or sniffing of a mothball is most common

  • Splenic sequestration in a child with sickle cell anemia or hereditary spherocytosis - Sudden onset of severe abdominal pain; shocklike state with a drop in hemoglobin and platelet count

Other history considerations

Symptoms of anemia include pallor, fatigue, lethargy, dizziness, and anorexia. Jaundice and, occasionally, dark urine may be present with significant hemolysis. Syncope and fainting are quite common in a teenager.

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.

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 Examination

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 usually asymptomatic.

To evaluate chronicity, plot growth parameters; this may affect the urgency of treatment. Also, note pallor, jaundice, edema, and signs of bleeding (eg, stool occult blood, frequent epistaxis, 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, wheezing, cough, distended neck vein, and 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 a sudden enlargement of the spleen and/or abdominal pain and distension together with an exacerbation of anemia and thrombocytopenia. 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, Fanconi anemia and, less often, Diamond-Blackfan anemia) may be associated with facial, limb, and other anomalies. Signs of hypothyroidism include low body temperature, failure to thrive, dry skin, constipation, and thinning of the hair.

 

DDx

Diagnostic Considerations

Conditions to consider, aside from those in the next section, in the differential diagnosis of acute anemia include the following:

  • Acute hemorrhage

  • Anemia of inflammation/infection

  • Aplastic anemia, due to blood loss

  • Autoimmune hemolytic anemia with acute hemolysis

  • Erythrophagocytosis (hemophagocytic lymphohistiocytosis [HLH])

  • G-6-PD deficiency, hemolytic episode

  • Hereditary spherocytosis, splenic sequestration, or acute hemolytic episode

  • Microangiopathic hemolytic anemia (DIC, Kasabach-Merritt phenomenon)

  • Paroxysmal cold hemoglobinuria

  • Paroxysmal nocturnal hemoglobinuria (PNH)

  • Hemolytic disease of newborn

  • Hemolytic-uremic syndrome

  • Acute porphyria

Conditions to consider, aside from those in the next section, in the differential diagnosis of chronic anemia include the following:

  • Chronic renal failure

  • Congenital dyserythropoietic anemia

  • Fanconi anemia

  • Iron deficiency anemia

  • Diamond-Blackfan anemia

  • Osteopetrosis

  • Sideroblastic anemia

  • Unstable hemoglobinopathy

  • Thymoma

  • Transient erythroblastopenia of childhood

  • Pyruvate kinase deficiency

  • Evans syndrome (ITP and autoimmune hemolytic anemia)

  • Hemoglobin H disease

  • Hypothyroidism

  • Myelofibrosis

  • Aplastic or hypoplastic anemia

  • Autoimmune hemolytic anemia

  • Pure red cell aplasia

  • PNH

Many anemias may be due to a combination of several mechanisms. For example, anemia due to acute infection is due to temporal suppression of erythropoiesis and some degree of hemolysis.

Differential Diagnoses

 

Workup

Approach Considerations

To evaluate anemia, obtain initial laboratory tests, including the complete blood count (CBC), reticulocyte count, and review of the peripheral smear. (See the diagram below.)

An overwhelming majority of acute anemia is normocytic, although marked reticulocytosis may raise mean corpuscular volume (MCV). If microcytic, it has an underlying chronic anemia component, and one needs to know the cause.

Algorithm for diagnostic approach and workup of an Algorithm for diagnostic approach and workup of anemia in children. Hb=hemoglobin; Hct=hematocrit; HS=hereditary spherocytosis; HE=hereditary elliptocytosis; G-6-PD=glucose-6-phosphate dehydrogenase; PK=pyruvate kinase; HUS=hemolytic uremic syndrome; TTP=thrombotic thrombocytopenic purpura; DIC=disseminated intravascular coagulation; DBA=Diamond-Blackfan anemia.

Chest radiography is performed in patients who may have CHF and to rule out mediastinal mass (associated with acute leukemia).

Abdominal ultrasonography is used to assess for gallstones or splenomegaly in hemolytic anemia, while computed tomography (CT) scanning is used to evaluate occult bleeding in blunt trauma (eg, splenic rupture, subcapsular hemorrhage of the liver) or a bleeding disorder. Abdominal Doppler study is used to detect portal vein thrombosis.

Radioactively tagged RBC radionuclide scans are occasionally used to localize the site of GI bleeding when the source is unclear (a common example in pediatrics is the Meckel scan, used in the diagnosis of Meckel diverticulum).

Family studies, such as sending the CBC count, smear review, and hemoglobin electrophoresis from parents, may be helpful in making a diagnosis of conditions such as hereditary spherocytosis or thalassemia.

Rarely indicated in isolated acute anemia, bone marrow aspiration and biopsy are indicated in the evaluation of possible bone marrow failure or malignancy. Suppression of the platelet count or white blood cell (WBC; neutrophil) count, in association with anemia, often warrants an examination of the bone marrow.

Magnetic resonance imaging in research settings

Recently, an MRI change termed acute silent cerebral ischemic events (ASCIE) in patients who developed acute anemia with and without sickle cell disease has been described.[1] The MRI abnormality is detected by diffusion-weighted imaging. The lesion may be temporary or long-lasting. If it is a permanent MRI lesion and the patient has no over clinical symptoms attributable to that lesion, then it is called a silent infarct. The fact that it occurs in children without sickle cell disease may indicate that in acutely severely anemic children regardless of the cause, ASCIE may not be a very rare event, and it does raise a question if some of these lesions are permanent and may cause subtle neurological dysfunction. Although MRI cannot be a routine imaging study for acute severe anemia, it may be a worthwhile test under a research setting.

Complete Blood Count

Base interpretation of the hemoglobin and hematocrit levels on the reference range for the specific age group. Some laboratories provide only a uniform reference range for the entire pediatric age group and not for specific age groups. Hemoglobin and hematocrit levels can be used interchangeably, depending on professional preference and familiarity. Essentially, the hematocrit level is 3 times the hemoglobin value.

If the patient is anemic, look at the red cell indices (mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH] and mean corpuscular hemoglobin concentration [MCHC]). Note that reference ranges for these parameters also vary with age. Of these, the MCV is particularly helpful in classifying anemia. Microcytic anemia suggests iron deficiency, lead poisoning, or thalassemia; macrocytosis suggests folate/B-12 deficiency or reactive reticulocytosis.

Another valuable parameter in classifying anemia is the RBC distribution width (RDW). This is the statistical description of the heterogeneity of RBC sizes. It is increased in anisocytosis (variable sizes of red cells), such as when increased reticulocytes are present.

Reticulocyte Count

Reticulocytes are immature, nonnucleated RBCs that indicate active erythropoiesis. The relative reticulocyte count is useful in differentiating whether the anemia is caused by decreased production, increased destruction, or loss of RBCs. An elevated number of reticulocytes (eventually) is observed in individuals with anemia caused by hemolysis or blood loss; note that the absence of reticulocytosis may simply reflect a "lag" in the response to the acute onset of anemia. Note that in some autoimmune hemolytic anemias, reticulocytopenia is present due to lysis of reticulocytes by the same antibodies.

The term reticulocyte count is often used inaccurately to refer to the percentage of reticulocytes, a value that must be interpreted in light of the degree of anemia. Thus, a finding of 2-3% reticulocytes (vs the normal value of approximately 1%) in a patient whose hemoglobin is only one third to one half of normal does not indicate a reticulocyte "response." Some clinicians prefer to use either the absolute number of reticulocytes per µL of blood or a reticulocyte percentage "corrected" for the degree of anemia, as follows: corrected reticulocyte count = patient hematocrit/normal hematocrit x %reticulocyte count.

Peripheral Smear

Examination of the peripheral smear helps to identify the cause of the anemia through recognition of abnormal cell morphology (this is particularly helpful in normocytic anemia). The following are examples of abnormal cell morphology:

  • Schistocytes or fragmented cells (microangiopathic hemolytic anemia)

  • Spherocytes (hereditary spherocytosis, autoimmune hemolytic anemia)

  • Ghost, helmet, blister, or bite cells (G-6-PD deficiency)

  • Sickle-shaped cells (sickle cell disease)

  • Target cells (hemoglobin C): These can be seen nonspecifically in other conditions, such as thalassemia, other hemoglobinopathies, and with liver disease; however, hemoglobin C is the classic, most common example

  • Stippled red blood cells (nonspecific, but may suggest lead poisoning; occurs in any condition with reticulocytosis)

  • Increased polychromasia (reticulocytosis)

  • Crenated or spiculated cells (liver disease, uremia, abetalipoproteinemia)

Recognizing that normal RBC morphology does not rule out hemolysis is important.

Additional Laboratory Tests

Additional laboratory tests that may be indicated in the diagnosis and treatment of patients with acute anemia include the following:

  • Bilirubin level, lactate dehydrogenase (hemolytic anemia)

  • Direct antiglobulin or Coombs test (autoimmune hemolytic anemia)

  • Hemoglobin electrophoresis (hemoglobinopathies) (many unstable hemoglobins, such as Hb KÖLN, cannot be detected by hemoglobin electrophoresis)

  • Red cell enzyme studies (eg, G-6-PD, pyruvate kinase)

  • Osmotic fragility (spherocytosis)

  • Iron, total iron-binding capacity (TIBC), ferritin (iron deficiency anemia)

  • Folate, vitamin B-12 (macrocytic/megaloblastic anemia)

  • Blood typing and crossmatching to assess possible isoimmune anemia in a neonate and to prepare for transfusion

  • Bone marrow aspiration and biopsy

  • Viral titers (eg, Epstein-Barr virus, cytomegalovirus)

  • Blood urea nitrogen (BUN) and creatinine levels to assess renal function

  • Thyroxine (T4)/thyroid-stimulating hormone (TSH) to rule out hypothyroidism

  • "Fetaldex test" on maternal blood (Kleihauer-Betke test), when fetomaternal transfusion is suspected

  • Stool for occult blood (on multiple specimens)

 

Treatment

Approach Considerations

Acute anemia usually warrants immediate medical attention. Treatment depends on the severity and underlying cause of the anemia.

Initial treatment begins with careful assessment of the signs and symptoms of the anemia that indicate therapy. Guidelines for the treatment of patients with critical illness apply to children with severe anemia who are in acute distress and unstable. Supportive measures, such as supplemental oxygen for decreased oxygen-carrying capacity, fluid resuscitation for hypovolemia, and bed rest or activity restriction for fatigue, may be required. Inpatient care is indicated in patients with CHF who are severely anemic and in those with unstable vital signs (eg, hypotension, active bleeding). Most of these patients require admission to the intensive care unit (ICU). Patients who may be stable but who have severe anemia may also be admitted for diagnostic workup.

Except in cases of uncontrolled hemorrhage, surgery is very rarely indicated in acute anemia. Splenectomy is occasionally considered in persons with autoimmune hemolytic anemia that is refractory to medical treatment.

Activity restriction or bed rest may be indicated in symptomatic individuals with severe anemia.

Transfusion

Transfusion with packed RBCs (PRBCs) is the universal treatment for most individuals with severe acute anemia. The British Committee for Standards in Hematology Transfusion Task Force has established guidelines for transfusions in neonates and older children.[12] and its amendments[13] The indication to transfuse should not be based solely on the hemoglobin or hematocrit levels; more importantly, one must consider the clinical effects or the signs and symptoms of the individual with anemia.[2]

A recently published article summarizing 19 randomized controlled studies in adults concluded that transfusions at a low Hb threshold level (7-9) compared with transfusions at a high Hb threshold level (9-13.3) showed a significantly reduced risk of 30-day all-cause mortality.[14] In another adult study with acute GI hemorrhage, restricted blood transfusion (Hb threshold of 7) versus a liberal transfusion strategy resulted in significantly reduced morbidity and mortality in the former group of patients.[15] While these are adult studies, the same principle may apply to children. Thus, one may consider these clear-cut study results when considering blood transfusion for a patient.

If transfusion is indicated, the packed RBC (PRBC) dose is 10-15 mL/kg over 3-4 hours. The rate of transfusion can be modified according to the clinical situation. Transfusion can be administered faster in individuals with acute blood loss or slower or in smaller aliquots in persons with CHF. Be aware of the risks of of inciting heart failure by rapid transfusion in patients with severe chronic anemia and patients in a compromised cardiovascular state.

In individuals with autoimmune hemolytic anemia, blood must be given with extreme caution, using the blood unit that is least reactive on crossmatch.

Consultations

Except for patients who have acute anemia secondary to blood loss from obvious trauma or injury, a hematology consultation is ideal for most patients with acute anemia to determine the underlying RBC disorder and provide the appropriate therapy.

In particular, the following features in an individual with acute anemia indicate the need for a hematology consultation:

  • Concomitant abnormality in WBC and/or platelet counts (eg, neutropenia, thrombocytopenia, presence of immature WBCs)

  • Positive Coombs test result

  • Hepatosplenomegaly

  • History of underlying hematologic disorder

  • Excessive blood loss relative to the degree of injury in individuals who may have an underlying bleeding disorder

Consider a gastroenterology consult for GI blood loss, particularly in suspected esophageal varices, inflammatory bowel disease, and other conditions.

Consider a surgical consult for possible trauma to spleen, liver, and/or kidneys.

 

Medication

Medication Summary

Medications for specific forms of anemia may be indicated in addition to blood transfusion (eg, corticosteroids for autoimmune hemolytic anemia, iron therapy for iron deficiency anemia).

Recombinant erythropoietin has been available for the treatment of certain forms of anemia. Its use can allow for avoidance or minimization of the need for blood transfusion. Indications include anemias of chronic disease (eg, renal failure), chemotherapy, acquired immunodeficiency syndrome (AIDS) treatment, preparation for surgery with anticipated significant blood loss, prematurity,[16] and hyporegenerative anemia of erythroblastosis fetalis. It is important to note that erythropoietin is not indicated for the immediate correction of anemia. The correction of anemia with erythropoietin occurs after about 2-8 weeks.

Blood Products

Class Summary

The goal of therapy in acute anemia is to restore the hemodynamics of the vascular system and replace lost red-blood cells. To achieve this, the practitioner may use blood transfusions. Major complications of acute anemia can be prevented by providing timely transfusion to restore hemoglobin to safe levels.

Packed red blood cells

Packed red blood cells (PRBCs) are used preferentially to whole blood since they limit volume, immune, and storage complications. PRBCs have 80% less plasma, are less immunogenic, and can be stored about 40 days (versus 35 days for whole blood). PRBCs are obtained after centrifugation of whole blood. Whole blood is not available in many blood banks. Currently, virtually all blood banks in the United States issue leukocyte-depleted (leukopoor) PRBCs. Leukopoor PRBCs prevent febrile transfusion reactions, leukocyte antigen–related allo-sensitization, and transmission of virus infections such as cytomegalovirus. Thus, they are a preferrable product compared with conventional PRBCs.

Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body’s immune response to diverse stimuli. They may be used in autoimmune hemolytic anemia.

Prednisolone (Prelone, Millipred)

Prednisolone decreases autoimmune reactions, possibly by suppressing key components of the immune system.

Methylprednisolone (Depo Medrol, Medrol, Solu-Medrol)

This agent is used for initial management of acute hemolytic anemia. Intravenous methylprednisolone is recommended when the most rapid and reliable treatment of hemolytic anemia is required.

Iron Salts

Class Summary

Iron salts are used for treating patients with iron deficiency anemia.

Ferrous Sulfate (Feosol, Fer-Iron, Slow FE)

Iron salts are used as building blocks for hemoglobin synthesis in treating anemia. They allow transportation of oxygen via hemoglobin and are necessary for oxidative processes of living tissue. Treatment should continue for about 2 months after correction of anemia and etiological cause in order to replenish body stores of iron. Ferrous sulfate is the most common and inexpensive form of iron utilized. Tablets contain 50-60 mg of iron salt. Other ferrous salts are used and may cause less intestinal discomfort because they contain smaller doses of iron (25-50 mg). Oral solutions of ferrous iron salts are available for use in pediatric populations.

 

Follow-up

Patient Education

In pediatrics beyond the immediate neonatal period, acute anemia is rare in otherwise healthy children. In most instances, it is due to blood loss, usually through the GI tract or via a heavy menstrual period. The most common reason for hospitalization due to acute anemia is so-called aplastic crisis in children with chronic hemolytic anemia who otherwise had been stable. Most common varieties are hereditary spherocytosis and sickle cell disease. Therefore it would be prudent to educate parents regarding this complication, at the time when the diagnosis is established.