eMedicine Specialties > Pediatrics: General Medicine > Hematology

Anemia, Acute: Differential Diagnoses & Workup

Author: Margaret T Lee, MD,, Associate Professor, Department of Pediatrics, Division of Pediatric Hematology, Children's Hospital of New York, Columbia University
Contributor Information and Disclosures

Updated: Apr 17, 2009

Differential Diagnoses

Other Problems to Be Considered

Acute blood loss
Anemia of inflammation/infection
Aplastic anemia
Autoimmune hemolytic anemia
Chronic renal failure
Congenital dyserythropoietic anemia
Diamond-Blackfan anemia
Erythrophagocytosis
Fanconi anemia
G-6-PD deficiency
Hereditary spherocytosis
Iron deficiency anemia
Microangiopathic hemolytic anemia
Osteopetrosis
Paroxysmal nocturnal hemoglobinuria
Pure red cell aplasia
Sideroblastic anemia
Unstable hemoglobinopathy

Workup

Laboratory Studies

• To evaluate anemia, obtain initial laboratory tests, including CBC count, reticulocyte count, and review of the peripheral smear (see Media file 1).
  
  

  

  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.

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  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.

  
  
  • 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], 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.
  • 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.
    • 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 mcl of blood or a reticulocyte percentage "corrected" for the degree of anemia. (Corrected reticulocyte count = patient hematocrit/normal hematocrit X %reticulocyte count)
  • Examination of the peripheral smear helps identify the cause of the anemia by recognizing abnormal cell morphology. The following are examples of abnormal cell morphology:
    • Schistocytes or fragmented cells (microangiopathic hemolytic anemia)
    • Spherocytes (hereditary spherocytosis, autoimmune hemolytic anemia)
    • Ghost 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 and other hemoglobinopathies; however, hemoglobin C is the classic, most common example.
    • Stippled red blood cells (nonspecific but may suggest lead poisoning)
    • 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 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)
  • 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)
  • BUN and creatinine levels to assess renal function
  • Thyroxine (T₄)/thyroid-stimulating hormone (TSH) to rule out hypothyroidism

Imaging Studies

• Chest radiography in patients who may have congestive heart failure (CHF) and to rule out mediastinal mass (associated with acute leukemia) or thymoma (associated with paroxysmal nocturnal hemoglobinuria)
• Abdominal ultrasonography to assess for gallstones or splenomegaly in hemolytic anemia
• CT scanning to evaluate occult bleeding in blunt trauma or bleeding disorder
• Radioactively tagged RBC radionuclide scans, occasionally used to localize site of GI bleeding when the source is unclear (a common example in pediatrics is Meckel scan used in the diagnosis of Meckel diverticulum)

Other Tests

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

Procedures

• 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 WBC (neutrophil) count, in association with anemia, often warrants an examination of the bone marrow.

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