Anemia is a hemoglobin (Hb) level two standard deviations below the mean for the age and sex of the patient. Reference ranges vary between laboratories. The World Health Organization defines anemia as:
Hb <11 g/dL in children under 5 years and in pregnant women
Hb <11.5 g/dL in children ages 5 to 11 years
Hb < 12 g/dL in children ages 12 to 14 years and in women (ages over 15 years)
Hb <13 g/dL in men (ages over 15 years)
The American Society of Hematology defines anemia as <13.5 g/dL in men and <12 g/dL in women.
Anemia 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.
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 (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).
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.
- Acute gastrointestinal bleeding
- Rupture of a vascular aneurysm
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
- Myelodysplastic syndrome
- Acute lymphocytic leukemia
- Acute myelogenous leukemia
- Chronic myelogenous leukemia
- Hairy cell leukemia
- Acquired aplastic anemia
- Infiltration by secondary malignancy
- Pure red cell aplasia
- Drug toxicity
- Anemia of chronic disease
- Chronic kidney disease
- Chronic liver disease
- Generalized malnutrition
- Cytotoxic chemotherapy
- Radiation therapy
- Alcohol abuse
- Lead toxicity
- Autoimmune hemolytic anemia
- Transfusion reaction
- Viral hepatitis
- Parvovirus B19 infection
- Infectious mononucleosis
- Cytomegalovirus (CMV)
- Sickle cell anemia
- Hereditary spherocytosis
- Glucose-6-phosphate dehydrogenase deficiency (G6PD)
- Bone marrow failure syndromes
- Hemolytic uremic syndrome
- Disseminated intravascular coagulation (DIC)
- Thrombotic thrombocytopenic purpura
- Malignant hypertension
- Prosthetic valves and surfaces
- Cutaneous burns
Robert Zaiden, MD
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 topic.
FR declares that she has no competing interests.
Christoph Pechlaner, MD
Associate Professor of Medicine
Innsbruck Medical University
CP declares that he has no competing interests.
John Densmore, MD, PhD
Associate Professor of Clinical Medicine
Department of Medicine
Division of Hematology/Oncology
University of Virginia
JD declares that he has no competing interests.
Carlos Aravena, MD
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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