Anemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Here is a simplified schematic of this approach:

Reticulocyte production index shows inadequate production response to anemia.
Reticulocyte production index shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem.
No clinical findings consistent with hemolysis or blood loss: pure disorder of production.
Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production*.
Clinical findings and normal MCV= acute hemolysis or loss without adequate time for bone marrow production to compensate**.
Macrocytic anemia (MCV>100)
Normocytic anemia (80<MCV<100)
Microcytic anemia (MCV<80)

* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause. ** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.

Classification Based on Red blood Cell Size

Here is a schematic representation of how to consider anemia with MCV as the starting point:

Macrocytic anemia (MCV>100)
Normocytic anemia (80<MCV<100)
Microcytic anemia (MCV<80)
High reticulocyte count
Low reticulocyte count

Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.

Microcytic Anemia

Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:

  • Heme synthesis defect
  • Globin synthesis defect
    • Alpha- and beta-thalassemia
    • HbE syndrome
    • HbC syndrome
    • Various other unstable hemoglobin diseases
  • Sideroblastic defect
    • Hereditary sideroblastic anemia
    • Acquired sideroblastic anemia including lead toxicity
    • Reversible sideroblastic anemia
  • Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
    • Iron deficiency anemia is caused by insufficient dietary intake or absorption of iron to replace losses from menstruation or losses due to diseases.[1] Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 20% of all women of childbearing age have iron deficiency anemia, compared with only 2% of adult men. The principal cause of iron deficiency anemia in premenopausal women is blood lost during menstruation. Studies have shown that iron deficiency without anemia causes poor school performance and lower IQ in teenage girls. Iron deficiency is the most prevalent deficiency state on a worldwide basis. Iron found in animal meats are more easily absorbed by the body than iron found in non-meat sources. In countries where animal meats are only occasionally available in the diet, iron deficiency anemia is six to eight times more prevalent than in North America and Europe. Iron deficiency is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular cheilitis).
    • Iron deficiency anemia can also be due to bleeding lesions of the gastrointestinal tract. Fecal occult blood testing, upper endoscopy and lower endoscopy should be performed to identify bleeding lesions. In men and post-menopausal women, the chances are higher that bleeding from the gastrointestinal tract could be due to a colon polyp or colorectal cancer.
    • Worldwide, the most common cause of iron deficiency anemia is of a parasitic infestation of(hookworm, amebiasis, schistosomiasis and whipworm).[2]
  • Hemoglobinopathies - much rarer (apart from communities where these conditions are prevalent)
    • Hb S Sickle-cell disease
    • Hb C
    • Hb E
    • Hb D-Punjab
    • Hb O-Arab
    • Hb G-Philadelphia
    • Hb Hasharon
    • Hb Korle-Bu
    • Hb Lepore
    • Hb M

A mnemonic commonly used to remember causes of microcytic anemia is TAILS: T - Thalassemia, A - Anemia of chronic disease, I - Iron deficiency anemia, L - Lead toxicity associated anemia, S - Sideroblastic anemia.

Normocytic Anemia

Normocytic anaemia occurs when the overall Hb levels are decreased, but the red blood cell size (MCV) remains normal. Causes include:

Macrocytic Anemia

  • Megaloblastic anemia is the most common cause of macrocytic anemia.
  • Megaloblastic anemia is due to a deficiency of either vitamin B12, folic acid (or both), or to autoimmune processes that cause deficiency in either, such as pernicious anemia. Deficiency in folate and/or Vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.
  • Alcoholism causes a macrocytosis, although not specifically anemia
  • Methotrexate, zidovudine, and other drugs that inhibit DNA replication. This is the most common etiology in nonalcoholic patients.

Dimorphic Anemia

When two causes of anemia act simultaneously, e.g., macrocytic hypochromic, due to hookworm infestation leading to deficiency of both iron and vitamin B12 or folic acid or following a blood transfusion more than one abnormality of red cell indices may be seen. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), which suggests a wider-than-normal range of red cell sizes.

Heinz Body Anemia

Heinz bodies are an abnormality that form on the cells in this condition. This form of anemia may be brought on by taking certain medications; it is also triggered in cats by eating onions.[3] or acetaminophen (Tylenol). It can be triggered in dogs by ingesting onions or zinc, and in horses by ingesting dry Red Maple leaves.

Specific Anemias

Anemia During Pregnancy