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Classifications and external resources
ICD- 10 D50-D64
ICD- 9 280- 285
DiseasesDB 663
MedlinePlus 000560
eMedicine med/132  emerg/808 emerg/734

Anaemia (AmE) or anaemia (BrE), from the Greek (Ἀναιμία) meaning "without blood", refers to a deficiency of red blood cells (RBCs) and/or hemoglobin. This results in a reduced ability of blood to transfer oxygen to the tissues, causing hypoxia; since all human cells depend on oxygen for survival, varying degrees of anaemia can have a wide range of clinical consequences. Hemoglobin (the oxygen-carrying protein in the red blood cells) has to be present to ensure adequate oxygenation of all body tissues and organs.

The three main classes of anaemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction ( hemolysis) or deficient red blood cell production (ineffective hematopoiesis). In menstruating women, dietary iron deficiency is a common cause of deficient red blood cell production.

Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anaemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few.

Different clinicians approach anemia in different ways; two major approaches of classifying anaemias include the "kinetic" approach which involves evaluating production, destruction and loss , and the "morphologic" approach which groups anaemia by red blood cell size. The morphologic approach uses a quickly available and cheap lab test as its starting point (the MCV). On the other hand, focusing early on the question of production (e.g., via the reticulocyte count) may allow the clinician more rapidly to expose cases where multiple causes of anemia coexist. Regardless of one's philosophy about the classification of anaemia, however, any methodical clinical evaluation should yield equally good results.

Signs and symptoms

Anemia goes undetected in many people, and symptoms can be vague. Most commonly, people with anemia report a feeling of weakness or fatigue, general malaise and sometimes a poor concentration. People with more severe anaemia sometimes report shortness of breath. Very severe anaemia prompts the body to compensate by increasing cardiac output, leading to palpitations and sweatiness, and to heart failure.

Pallor (pale skin, mucosal linings and nail beds) is often a useful diagnostic sign in moderate or severe anaemia, but it is not always apparent.


The only way to diagnose most cases of anaemia is with a blood test. Generally, clinicians order a full blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anaemia. A visual examination of a blood smear can also be helpful, and is sometimes a necessity in regions of the world where automated analysis is less accessible.

In modern counters, four parameters (RBC Count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. For males, the hemoglobin level that is suggestive of anaemia is usually less than 13.0 g/dl, and for females, it is less than 12.0 g/dl.

Depending on the clinical philosophy, whether the hospital's automated counter can immediately add it to the initial tests, and the clinicians' attitudes towards ordering tests, a reticulocyte count may be ordered either as part of the initial workup or during followup tests. This is a nearly direct measure of the bone marrow's capacity to produce new red blood cells, and is thus the most used method of evaluating the problem of production. This can be especially important in cases where both loss and a production problem may co-exist. Many physicians use the reticulocyte production index – a calculation of the ratio between the level of anaemia and the extent to which the reticulocyte count has risen in response. Even in cases where an obvious source of loss exists, this helps evaluate whether the bone marrow will be able to compensate for the loss, and at what rate.

When the cause is not obvious, clinicians use other tests to further distinguish the cause for anaemia. These are discussed with the differential diagnosis, below. A clinician may also decide to order other screening blood tests that might identify the cause of fatigue; serum glucose, ESR, ferritin, serum iron, RBC folate level, serum vitamin B12, renal function tests (e.g. serum creatinine) and electrolytes may be part of such a workup.


Production vs. destruction or loss

The "kinetic" approach to anemia yields what many argue is the most clinically relevant classification of anaemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction and/or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guiaic-positive stool, radiographic findings, or frank bleeding.

Here is a simplified schematic of this approach:

Reticulocyte production index shows inadequate production response to anaemia.
Reticulocyte production index shows appropriate response to anaemia = 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 anaemia (MCV>100)
Normocytic anaemia (80<MCV<100)
Microcytic anaemia (MCV<80)

* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anaemia 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 anaemia of chronic disease, with superimposed or related hemolysis or blood loss.

Red blood cell size

In the morphological approach, anaemia is classified by the size of 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 anaemia 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 anaemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anaemia is often the result of iron deficiency. In clinical workup, the MCV will be one of the first pieces of information available; so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.

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

Macrocytic anaemia (MCV>100)
Normocytic anaemia (80<MCV<100)
Microcytic anaemia (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 anaemia

  • Iron deficiency anaemia is the most common type of anemia overall, and it is often hypochromic microcytic. Iron deficiency anaemia 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 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 anaemia in premenopausal women is blood lost during menses. Studies have shown that iron deficiency without anaemia causes poor school performance and lower IQ in teenage girls.

In older patients, iron deficiency anaemia is often due to bleeding lesions of the gastrointestinal tract; fecal occult blood testing, upper endoscopy and lower endoscopy are often performed to identify bleeding lesions, which can be malignant. Iron deficiency is the most prevalent deficiency state on a worldwide basis. Iron deficiency affects women from different cultures and ethnicities. Iron found in animal meats are more easily absorbed by the body than iron found in non-meat sources. In countries where meat consumption is not as common, iron deficiency anaemia is six to eight times more prevalent than in North America and Europe. This is due to the importance of meat in the diets of North Americans and Europeans. Iron deficiency is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips ( angular cheilitis).

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

  • Heme synthesis defect
    • Iron deficiency
    • Anaemia of Chronic Disorders (which, sometimes, is grouped into normocytic anaemia)
  • Globin synthesis defect
    • alpha-, and beta-thalassemia
    • HbE syndrome
    • HbC syndrome
    • and various other unstable hemoglobin diseases
  • Sideroblastic defect
    • Hereditary Sideroblastic anaemia
    • Acquired Sideroblastic anaemia including lead toxicity
    • Reversible Sideroblastic anaemia

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

Normocytic anaemia

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

  • Acute blood loss
  • Anaemia of chronic disease
  • Aplastic anaemia (bone marrow failure)

Macrocytic anaemia

  • Megaloblastic anaemia due to 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. Megaloblastic anemia is the most common cause of macrocytic anaemia.
  • Pernicious anaemia is an autoimmune condition directed against the parietal cells of the stomach. Parietal cells produce intrinsic factor, required to absorb vitamin B12 from food. Therefore, the destruction of the parietal cells causes a lack of intrinsic factor, leading to poor absorption of vitamin B12.
  • Alcoholism
  • Methotrexate, zidovudine, and other drugs that inhibit DNA replication. This is the most common etiology in nonalcoholic patients.

Macrocytic anemia can be further divided into "megaloblastic anemia" or "non-megaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which result in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (6-10 lobes). The non-megaloblastic macrocytic anaemias have different etiologies (i.e. there is unimpaired DNA synthesis,) which occur, for example in alcoholism.

The treatment for vitamin B12-deficient macrocytic and pernicious anaemias was first devised by William Murphy who bled dogs to make them anaemia 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. Symptoms of vitamin B12 deficiency include having a smooth, red tongue.

Dimorphic anaemia

Here there are two types of anaemia 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. One hint that this kind of anaemia may exist is a wide RBC distribution width (RDW), which suggests a wider-than-normal range of sizes of red blood cells.

Specific anaemias

  • Fanconi anaemia is an hereditary disorder or defect featuring aplastic anaemia and various other abnormalities
  • Hemolytic anaemia causes a separate constellation of symptoms (also featuring jaundice and elevated LDH levels) with numerous potential causes. It can be autoimmune, immune, 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 anaemia.
  • Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. This leads to a decrease in the number of circulating RBCs and, hence, anaemia.
  • Sickle-cell anaemia, a hereditary disorder, is due to the presence of the mutant hemoglobin S gene.
  • Warm autoimmune hemolytic anaemia is an anaemia caused by autoimmune attack against red blood cells, primarily by IgG
  • Cold Agglutinin hemolytic anaemia is primarily mediated by IgM

Possible complications

Anaemia diminishes the capability of individuals who are affected to perform physical labor. This is a result of one's muscles being forced to depend on anaerobic metabolism. The lack of iron associated with anaemia can cause many complications, including hypoxemia, brittle or rigid fingernails, cold intolerance, impaired immune function, and possible behavioural disturbances in children.

Hypoxemia resulting from anemia can worsen the cardio-pulmonary status of patients with pre-existing chronic pulmonary disease. Brittle or rigid fingernails may be a result of abnormal thinness of nails due to insufficient iron supply. Cold intolerance occurs in one in five patients with iron deficiency anaemia, and becomes visible through numbness and tingling. Impaired immune functioning leading to increased likelihood of sickness is another possible complication.

Doctors attempt to avoid blood transfusion in general, but there are several instances where doctors are now more aggressive than in the past. For instance, the currently accepted Rivers protocol for early goal directed therapy for sepsis requires keeping the hematocrit above 30; this is based on evidence that even moderate anaemia reduces survival . The presumed physiological principle is that the reduction in oxygen delivery associated with anaemia is especially dangerous to people who are already at risk for organ damage from lack of perfusion. There is controversy about what hematocrit or hemoglobin levels should be used as "triggers" for transfusion in other settings. Anaemia also may be especially risky for people with acute coronary syndromes, again because anaemia hampers already-impaired oxygen delivery to the heart. However, the point at which this danger emerges in other settings is controversial and awaits further study.

Finally, chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced scholastic performance in children of school age. Behavioural disturbances may even surface as an attention deficit disorder.

Anaemia during pregnancy

Anaemia affects 20% of all females of childbearing age in the United States. Because of the subtlety of the symptoms, women are often unaware that they have this disorder, as they attribute the symptoms to the stresses of their daily lives. Possible problems for the fetus include increased risk of growth retardation, prematurity, intrauterine death, rupture of the amnion and infection.

During pregnancy, women should be especially aware of the symptoms of anaemia, as an adult female loses an average of two milligrams of iron daily. Therefore, she must intake a similar quantity of iron in order to make up for this loss. Additionally, a woman loses approximately 500 milligrams of iron with each pregnancy, compared to a loss of 4-100 milligrams of iron with each period. Possible consequences for the mother include cardiovascular symptoms, reduced physical and mental performance, reduced immune function, tiredness, reduced peripartal blood reserves and increased need for blood transfusion in the postpartum period.

Diet and anaemia

Consumption of food rich in iron is essential to prevention of iron deficiency anemia; however, the average adult has approximately nine years worth of B12 stored in the liver, and it would take four to five years of an iron-deficient diet to create iron-deficiency anaemia from diet alone.

Iron-rich foods include red meat; green, leafy vegetables; dried beans; dried apricots, prunes, raisins, and other dried fruits; almonds; seaweeds; parsley; whole grains; and yams. In extreme cases of anaemia, researchers recommend consumption of beef liver, lean meat, oysters, lamb or chicken, or iron drops/tablets may be introduced. Certain foods have been found to interfere with iron absorption in the gastrointestinal tract, and these foods should be avoided. They include tea, coffee, wheat bran, rhubarb, chocolate, soft drinks, red wine, ice cream, and candy bars (Bauer, 2). With the exception of milk and eggs, animal sources of iron provide iron with better bioavailability than vegetable sources (Scrimshaw).

Treatments for anaemia

There are many different treatments for anemia, including increasing dietary intake of readily available iron and iron supplementation; the treatment is determined by the type of anaemia that is diagnosed.

If an increase in dietary intake is prescribed, then additionally increasing one's intake of Vitamin C may aid in the body's ability to absorb iron.

In anemia of chronic disease, anemia associated with chemotherapy, or anaemia associated with renal disease, some clinicians prescribe a recombinant protein version of erythropoietin, epoetin alfa, to stimulate red blood cell production.

In severe cases of anaemia, a blood transfusion may be necessary.

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