Evaluation of anemia

Last reviewed: March 2020

Last updated: March 2019

Summary

Anemia is defined as a hemoglobin (Hb) level <12 g/dL in females and <14 g/dL in males or, alternatively, as an Hb level <12.5 g/dL in adults.[1][2][3] It is the most common hematologic disorder seen in general medical practice. Risk factors include extremes of age, female sex, lactation, and pregnancy. The most common cause internationally is iron deficiency.[4] Anemia can cause significant morbidity if left untreated, and is often the presenting sign of a more serious underlying condition.[5] The rate at which anemia develops is often as important as the severity, as a rapid decline can overwhelm the compensatory mechanisms of the body.

Pathophysiology

Erythropoiesis takes place within the bone marrow and is controlled by the stromal network, cytokines, and the hormone erythropoietin. A series of differentiation steps results in the generation of reticulocytes (red blood cells [RBCs] with an intact ribosomal network). Reticulocytes remain in the bone marrow for 3 days before being released into the circulation. After one further day in the circulation, reticulocytes lose their ribosomal network and become mature RBCs, which circulate for 110-120 days before being removed from the circulation by macrophages. At steady state, the rate of RBC production equals the rate of RBC loss. Anemia develops when the rate of RBC production decreases and/or the rate of RBC loss increases.

Morphological classification of anemia

The most clinically useful classification system is based on the mean corpuscular volume (MCV).[6][7][8]

Microcytic (MCV <80 femtoliters [fL]). [Figure caption and citation for the preceding image starts]: Microcytic anemiaFrom the collection of Dr Robert Zaiden; used with permission [Citation ends].
Normocytic (MCV 80-100 femtoliters [fL]); further subclassified according to the reticulocyte count as:
- Hyperproliferative (reticulocyte count >2%): the proportion of circulating reticulocytes increases as part of a compensatory response to increased destruction or loss of RBCs. The cause is usually acute blood loss or hemolysis.
- Hypoproliferative (reticulocyte count <2%): these are primarily disorders of decreased RBC production, and the proportion of circulating reticulocytes remains unchanged.
Macrocytic (MCV >100 femtoliters [fL]); further subclassified as:
- Megaloblastic: a deficiency of DNA production or maturation resulting in the appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation.
- Nonmegaloblastic: encompasses all other causes of macrocytic anemia in which DNA synthesis is normal. Megaloblasts and hypersegmented neutrophils are absent.[Figure caption and citation for the preceding image starts]: Megaloblastic macrocytic anemiaFrom the collection of Dr Robert Zaiden; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Classification of anemia: MCV, mean corpuscular volume; fL, femtolitersCreated by the BMJ Knowledge Centre [Citation ends].