Anemia

Anemia, a clinical finding that arises from many etiologies, is defined by a hemoglobin (Hb) value at least 2 standard deviations below the mean for age and sex (<13 g/dL for men and <12 g/dL for women), although Hb values may vary due to pregnancy, race, smoking, or altitude. Severe anemia is defined as Hb <8 g/dL in people of all ages and in both sexes, except in children 6-59 months of age and pregnant women. Anemia results in nonspecific tissue hypoxia symptoms (eg, fatigue, weakness, pallor, dizziness, and fainting). More than one billion individuals are affected by anemia worldwide, and iron deficiency anemia accounts for approximately half of anemia cases. Additional anemias include anemia of chronic disease/anemia of inflammation (anemia related to infections, inflammation, obesity, cancer, and other causes), megaloblastic anemia (caused by vitamin B12 and/or folate deficiency), hemolytic anemias (including sickle cell anemia), and aplastic anemias (related to bone marrow disorders), among others. As anemia treatment depends on the underlying cause, identifying the correct etiology is essential. Initial anemia evaluation includes CBC with platelet count and automated differential, a reticulocyte count and percent, along with a corrected reticulocyte count, and in some cases, review of a peripheral blood smear. Certain circumstances may warrant a bone marrow biopsy.    

Quick Answers for Clinicians

What is the testing strategy to identify the etiology of anemia?

Testing for anemia includes CBC with platelet count and automated differential. A CBC includes red blood cell (RBC) indices that can be used to further classify anemia, suggesting possible diagnoses and additional testing. A reticulocyte count is commonly ordered with a CBC to assess bone marrow response to anemia. Peripheral blood smears may be used to rapidly identify specific anemias that result in distinctive cellular morphologies. Additional testing, including serum ferritin and iron and iron binding capacity tests, may be performed to reach a definitive diagnosis.  See the Anemia Testing Algorithm.

What is the recommended screening strategy for anemia?

In general, screening for anemia depends on the needs of the patient. Symptomatic patients should be screened on presentation. The U.S. Preventive Services Task Force finds insufficient evidence to recommend universal screening. The American Academy of Family Practice, however, recommends universal screening at 12 months of age, and the American College of Obstetrics and Gynecology recommends that all pregnant women be screened. 

Why is it important to obtain a corrected reticulocyte count?

The reticulocyte count is an important indicator of bone marrow production of new red blood cells (RBCs). However, anemia leads to a decrease in the number of RBCs, and thus a falsely elevated percentage of reticulocytes. A corrected reticulocyte count adjusts for anemia, thereby allowing assessment of erythropoiesis and detection of conditions associated with consumption or destruction of RBCs.

Indications for Testing

Testing for anemia is appropriate when patients present with symptoms of tissue hypoxia (including fatigue, weakness, pallor, dizziness, fainting, shortness of breath, and irregular heartbeat), or when a routine screening test reveals an Hb value at least 2 standard deviations below the mean for age and sex.

Laboratory Testing

Initial Evaluation

Complete Blood Count

The first recommended test in the evaluation of suspected anemia is a CBC, which includes an assessment of hematocrit (Hct), Hb, platelets, red blood cell (RBC) and white blood cell (WBC) counts, and RBC indices. Mean corpuscular volume (MCV) from the CBC will guide further testing. 

RBC Size Possible Etiologies Next Step Associated Consult Topics
Low MCV (microcytosis)

Iron deficiency anemia (most common)

Anemia of chronic disease/anemia of inflammation

Thalassemia

Sideroblastic anemia

Lead toxicity

Some hemoglobinopathy traits

Iron parameters, HPLC evaluation for thalassemia Iron Deficiency Anemia

Thalassemias

Lead Poisoning

Normal MCV (normocytosis)

Anemia of chronic disease/anemia of inflammation (most common)

Acute blood loss

Early or partially treated vitamin or iron deficiencies

Hemolysis

Renal insufficiency

Bone marrow infiltration (leukemia/lymphoma, metastatic disease, granulomatous disease)

Hemoglobinopathies

Aplastic anemia/pure red cell aplasia

Hereditary spherocytosis

Sickle cell disease

Corrected reticulocyte count Anemia of Chronic Disease/Anemia of Inflammation

Hemolytic Anemias

Hemoglobinopathies

High MCV (macrocytosis)

Folate and/or vitamin B12 deficiency

Drug use

Alcohol abuse (very common)

Thyroid disease

Liver disease

Myelodysplasia

Hemolytic anemias

Aplastic anemia

Corrected reticulocyte count, vitamin B12 and folic acid levels Megaloblastic Anemia
HPLC, high-performance liquid chromatography

Reticulocyte Count

A reticulocyte count, corrected for anemia (corrected reticulocyte count), is an indicator of bone marrow production of new RBCs  and should be ordered in cases of normal or high MCV. The corrected reticulocyte count is elevated in several disease states, including conditions with consumption or destruction of RBCs such as hemolytic anemias, and is normal or decreased in conditions such as megaloblastic and aplastic anemia.  If there is evidence of bone marrow dysfunction, a peripheral smear should be ordered.

Peripheral Smear

A peripheral smear is used to evaluate cellular morphology, which may suggest a specific etiology for observed anemia.  An abnormal smear should always be investigated based on smear characteristics, regardless of any cellular indices.  Bone marrow biopsy may be necessary.

RBC Morphology Possible Etiology Associated ARUP Consult Topics
Burr cells Artifact, uremia Consider evaluation for kidney disease (no applicable ARUP Consult Topic)
Fragmented RBCs (eg, schistocytes, helmet cells) Hemolytic disease Hemolytic Anemias
Increased zone of central pallor with anisocytosis and poikilocytosis Iron deficiency Iron Deficiency Anemia
Hypersegmented neutrophils Megaloblastic anemia Megaloblastic Anemia
Teardrops in RBCs Myelofibrosis Myeloproliferative Neoplasms
Sickle cells Sickle cell anemia Hemolytic Anemias
Spherocytes Hereditary or immune-mediated hemolytic anemias Hemolytic Anemias
Heinz body stain positive Hemoglobinopathies Hemoglobinopathies
Unusual RBC inclusions Infection

Plasmodium Species – Malaria

Babesia microti – Babesiosis

Bartonella Species – Bartonellosis

Indications for Bone Marrow Biopsy

Although not generally recommended, bone marrow biopsy may be appropriate when laboratory testing proves to be inadequate to reach a diagnosis,  or when clinical suspicion of iron deficiency persists, regardless of laboratory test results. Bone marrow biopsy may also be required when abnormalities in blood counts and/or a peripheral blood smear are observed, for example, in unexplained cytopenias, unexplained leukocytosis, or when abnormal WBCs, teardrop cells, or rouleaux are observed.  Finally, bone marrow biopsy may be required in the evaluation of diseases such as splenomegaly or lymphadenopathy, in tumor staging, or in other complex clinical contexts. 

ARUP Laboratory Tests

Initial Evaluation

First recommended test in the evaluation of suspected anemia

Assess erythropoiesis in hematologic conditions

Evaluate cellular morphology

Additional Tests

Aid in the diagnosis of iron deficiency anemia

Aid in the detection of vitamin B12 deficiency in individuals with macrocytic or unexplained anemia

Medical Experts

Contributor

Agarwal

Archana Mishra Agarwal, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Hematopathology and Special Genetics, ARUP Laboratories
Contributor

Pearson

Lauren N. Pearson, DO, MPH
Assistant Professor of Clinical Pathology, University of Utah
Laboratory Director for ARUP at University of Utah Health and Huntsman Cancer Institute
Laboratory Director, South Jordan and Sugarhouse Health Center Clinical Laboratories

References

Resources from the ARUP Institute for Clinical and Experimental Pathology®