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.    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.  Anemia can cause significant morbidity if left untreated, and is often the presenting sign of a more serious underlying condition.  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.
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.   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.
Microcytic (MCV <80 femtoliters [fL]).
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.
Baptist MD Anderson Cancer Center
RZ declares that he has no competing interests.
Dr Robert Zaiden would like to gratefully acknowledge Dr Fauzia Rana, a previous contributor to this monograph. FR declares that she has no competing interests.
Associate Professor of Medicine
Innsbruck Medical University
CP declares that he has no competing interests.
Associate Professor of Clinical Medicine
Department of Medicine
Division of Hematology/Oncology
University of Virginia
JD declares that he has no competing interests.
Internal Medicine Instructor
Member of Evidence Based Medicine Unit
Catholic University of Chile
CA declares that he has no competing interests.
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