Evaluation of anemia

Anemia is defined as a hemoglobin (Hb) level <12 g/dL in females and <14 g/dL in males, or as a Hb level <12.5 g/dL in adults. [1] Report of WHO/UNICEF/UNU consultation on indicators and strategies for iron deficiency and anemia programmes. In: WHO/UNICEF/UNU consultation. Geneva, Switzerland: WHO; 1994. [2] Lee GR, Foerster J, Lukens J. Wintrobe's clinical hematology. 10th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 1999. [3] Beutler E, Lichtman MA, Coller BS, et al. Williams hematology. 6th ed. New York, NY: McGraw-Hill; 2000. It is the most common hematologic disorder seen in general medical practice. Risk factors include extremes of age, female gender, lactation, and pregnancy. The most common cause internationally is iron deficiency. [4] Brown RG. Anemia. In: Taylor RB, ed. Family medicine: principles and practice. 4th ed. New York, NY: Springer-Verlag; 1994:997-1005. Anemia can cause significant morbidity if left untreated, and is often the presenting sign of a more serious underlying condition. [5] Thein M, Ershler WB, Artz AS, et al. Diminished quality of life and physical function in community-dwelling elderly with anemia. Medicine (Baltimore). 2009;88:107-114. http://www.ncbi.nlm.nih.gov/pubmed/19282701?tool=bestpractice.com 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 (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 to 120 days before being removed from the circulation by macrophages. At steady state, the rate of RBC production equals the rate of RBC loss.

Hemolytic anemias are a group of anemias produced by increased destruction of RBCs with a resultant increase in circulating indirect bilirubin. [6] Zuckerman KS. Approach to the anemias. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007: chapter 162. [7] Glader BE. Hemolytic anemia in children. Clin Lab Med. 1999;19:87-111,vi. http://www.ncbi.nlm.nih.gov/pubmed/10403076?tool=bestpractice.com Clinical jaundice appears once bilirubin levels rise above 2 to 4 mg/dL. Additional disease-specific symptoms may also be present. The resulting anemia can be microcytic or hyperproliferative normocytic, depending on the cause.

Microangiopathic hemolytic anemias are often considered as a group. They produce a hyperproliferative normocytic anemia. The underlying disease process produces endothelial damage and activates the coagulation cascade, leading to fibrin deposition on the damaged endothelial surfaces. In small vessels, the endothelial fibrin causes mechanical fragmentation and shearing of RBCs, leading to hemolysis. The irregular-shaped RBC fragments produced by this process are called schistocytes and can be seen on a peripheral blood smear.

Morphological classification of anemia

The most clinically useful classification system is based on the mean corpuscular volume (MCV). [8] Ginder GD. Microcytic and hypochromic anemias. In: Goldman L, Ausiello DA, eds. Cecil Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007: chapter 163. [9] Brill JR, Baumgardner DJ. Normocytic anemia. Am Fam Physician. 2000;62:2255-2264. http://www.aafp.org/afp/2000/1115/p2255.html http://www.ncbi.nlm.nih.gov/pubmed/11126852?tool=bestpractice.com [10] Davenport J. Macrocytic anemia. Am Fam Physician. 1996;53:155-162. http://www.ncbi.nlm.nih.gov/pubmed/8546042?tool=bestpractice.com

• Microcytic (MCV <80 femtoliters [fL]). [Figure caption and citation for the preceding image starts]: Microcytic anemia From 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. [Figure caption and citation for the preceding image starts]: Megaloblastic macrocytic anemia From the collection of Dr Robert Zaiden; used with permission [Citation ends].

  • 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]: Classification of anemia: MCV, mean corpuscular volume; fL, femtoliters Created by the BMJ Knowledge Centre [Citation ends].