Pediatric Acute Anemia Workup

Updated: Sep 22, 2021
  • Author: Susumu Inoue, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
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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 congestive heart failure (CHF) and to rule out mediastinal mass (associated with acute leukemia or lymphoma).

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 CBC, blood 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 used for the evaluation of possible bone marrow failure such as transient erythroblastopenia of childhood (TEC), malignancy, or congenital dyserythropoietic anemia. 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

A magnetic resonance imaging (MRI) abnormality termed an acute silent cerebral ischemic event (ASCIE), in patients who developed acute anemia with and without sickle cell disease, has been described. [2] An ASCIE 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 overt 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) - A mere mention of schistocytes in the CBC comments does not suggest the specific diagnosis; a study demonstrated that up to 3% of RBCs examined in the blood smears of patients with, for example, cancer, prematurity, megaloblastic anemia, renal failure, sepsis, or iron deficiency anemia contained schistocytes [17]

  • 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) [18]

  • 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)