Anemia - Macrocytic , Microcytic and Normocytic

Anemia (American English) or anaemia (British English) is a lack of red blood cells and/or hemoglobin. This results in a reduced ability of blood to transfer oxygen to the tissues. Hemoglobin (the oxygen-carrying protein in the red blood cells) has to be present to ensure adequate oxygenation of all body tissues.

Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anemia is classified by the size of the red blood cell: decreased (microcytic), normal (normocytic) or enlarged (macrocytic or megaloblastic).


Signs and symptoms

Anemia goes undetected in many people, and symptoms can be vague. Most commonly, a feeling of weakness or fatigue is reported. Shortness of breath is reported in more severe cases. Very severe anemia prompts a compensatory response where cardiac output is markedly increased, leading to palpitations and sweatiness; this process can lead to heart failure in elderly people.

Pallor (pale skin and mucosal linings) is only notable in cases of severe anemia, and is therefore not a reliable sign.


The only way to diagnose anemia is with a blood test. Generally, a full blood count is done. Apart from reporting the amount of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells, which is an important tool in distinguishing between the causes.

Occasionally, other tests are required to further distinguish the cause for anemia. These are discussed with the differential diagnosis (below). The doctor may also decide to take some other screening blood tests that might identify the cause of fatigue; glucose levels, ESR, ferritin, renal function tests and electrolytes may be part of such a workup.

Differential diagnosis

Anemia is classified by the size of the red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80-100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. 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

The most common type of anemia overall is iron deficiency anemia, which is most often microcytic. Much rarer causes (apart from communities where these conditions are prevalent)are hemoglobinopathies such as sickle cell anaemia and thalassemia.

Iron deficiency anemia is caused when the dietary intake or absorption of iron is insufficient. Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red 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 menses. Studies have shown that iron deficiency without anemia causes poor school performance and lower IQ in teenage girls. In older patients, iron deficiency anemia of often due to bleeding lesions of the gastrointestinal tract; fecal occult blood testing, upper and lower endoscopy are often performed to identify bleeding lesions, which can be malignant.

Normocytic anaemia

Normocytic anemia can be caused by acute blood loss, chronic disease ("anemia of chronic disease") or failure to produce enough red blood cells (as opposed to hemoglobin, which causes microcytic anemia). Chronic renal failure or liver failure cause normocytic anemia; in renal failure this is due to decreased production of the hormone erythropoietin.

Certain hormonal deficiencies, like testosterone deficiency (hypogonadism), can cause normocytic anemia. Lastly, sideroblastic anemia is caused by abnormal production of red blood cells as part of myelodysplastic syndrome, which can evolve into hematological malignancies (especially acute myelogenous leukemia).

Aplastic anemia (bone marrow failure) is anemia caused by the inability of the bone marrow to produce blood cells. Aplastic anemias are much rarer than dietary deficiency or genetic defect anemias, and progess rapidly.

Macrocytic anaemia

The most common cause of macrocytic anemia is a deficiency of either vitamin B12 or folic acid (or both) due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does. Pernicious anemia is an autoimmune condition where the body lacks intrinsic factor, required to absorb vitamin B12 from food. Alcoholism can cause macrocytic anemia. 

The treatment for vitamin B12-deficient macrocytic and pernicious anemias was first devised by William Murphy who bled dogs to make them anemic and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. George Minot and George Whipple then set about to chemically isolate the curative substance and ultimately were able to isolate the vitamin B12 from the liver. For this, all three shared the 1934 Nobel Prize in Medicine.

Specific anemias

Fanconi anemia - a hereditary disease featuring aplastic anemia and various other abnormalities .

Hemolytic anemia is a separate constellation of symptoms (also featuring jaundice and elevated LDH levels) with numerous potential causes. It can be autoimmune, hereditary or mechanical (e.g. heart surgery). It can result (because of cell fragmentation) in a microcytic anemia, a normochromic anemia, or (because of premature release of immature red blood cells from the bone marrow), a macrocytic anemia


Related articles:
Iron for runners, erythropoietin, testosterone

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