Information Source for Anemia or Anaemias



Anemia or anaemias, from the Greek (ναιμία ) 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 anemias 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.

There are three main classes of anemia 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. Anemia 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.

There are two major approaches of classifying anemias, the "kinetic" approach which involves evaluating production, destruction and loss, and the "morphologic" approach which groups anemia 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 may allow the clinician more rapidly to expose cases where multiple causes of anemia coexist.

Signs and Symptoms of Anemia or Anaemias

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 anemia often report dyspnea (shortness of breath) on exertion. Very severe anemia 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. Other useful signs are cheilosis and koilonychia.

Diagnosis of Anemia or Anaemias

Generally, clinicians request complete blood counts in the first batch of blood tests in the diagnosis of a suspected anaemia. 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 anemia. Examination of a stained blood smear using a microscope 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 anemias is usually less than 13.0 g/dl, and for females, it is less than 12.0 g/dl.

Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte count is a quantitative measure of the bone marrow's capacity to produce new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response, thus indicating whether a "normal" reticulocyte count actually may reflect an inadequate response to anemia.

If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis can help assess 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 anemias. A clinician may also decide to request other 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 tests. When the diagnosis remains difficult another test the bone marrow biopsy can be used to assesses the bone marrow more directly.

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Classification of Anemia or Anaemias

Production vs Destruction or Loss of Anemia or Anaemias

The "kinetic" approach to anemia yields what many argue is the most clinically relevant classification of anemia. 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.

Red Blood Cell Size

In the morphological approach, anemia 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 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. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. In clinical work ups, 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.

Microcytic Anemia

  • Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs on often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
    • Iron deficiency anemia is commonly caused by insufficient dietary intake or absorption of iron. 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 menses. 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 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 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 due to bleeding lesions of the gastrointestinal tract. Fecal occult blood testing, upper endoscopy and lower endoscopy are often performed to identify bleeding lesions. In elderly people the chances are higher that bleeding from the gastrointestinal tract could be due to a cancer.
  • Hemoglobinopathies -- much rarer (apart from communities where these conditions are prevalent)
    • Sickle-cell disease
    • Thalassemia

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

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

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

  • Acute blood loss
  • Anemia of chronic disease
  • Aplastic anemia (bone marrow failure)

Macrocytic Anemia

  • Megaloblastic anemia 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 anemia.
  • Pernicious anemia 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 hyper segmentation (6-10 lobes). The non-megaloblastic macrocytic anemias 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 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. Symptoms of vitamin B12 deficiency include having a smooth, red tongue.

Dimorphic Anemia

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

Specific Anemias

  • Fanconi anemia is an hereditary disorder or defect featuring aplastic anemia and various other abnormalities
  • Hemolytic anemia 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 anemia.
  • 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, anemia.
  • Sickle-cell anemia, a hereditary disorder, is due to the presence of the mutant hemoglobin S gene.
  • Warm autoimmune hemolytic anemia is an anemia caused by autoimmune attack against red blood cells, primarily by IgG
  • Cold Agglutinin hemolytic anemia is primarily mediated by IgM

Possible Complications of Anemia or Anaemias

Anemia 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 anemia can cause many complications, including hypoxemia, brittle or rigid fingernails, cold intolerance, impaired immune function, and possible behavioral disturbances in children.

Hypoxemia resulting from anemia can worsen the cardiopulmonary 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 anemia, 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 anemia reduces survival. The presumed physiological principle is that the reduction in oxygen delivery associated with anemia 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. Anemia also may be especially risky for people with acute coronary syndromes, again because anemia 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. Behavioral disturbances may even surface as an attention deficit disorder.

Anemia During Pregnancy

Anemia 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 anemia, 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 Anemia

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 anemia from diet alone.

Iron-rich foods include red meat; green, leafy vegetables; beans; dried apricots, prunes, raisins, and other dried fruits; almonds; seaweeds; parsley; whole grains; and yams. In extreme cases of anemia, 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 bio availability than vegetable sources (Scrimshaw).

Treatments for Anemia

There are many different treatments for anemia and the treatment depends on the cause.

When serious causes of an anemia have been excluded, a mild iron deficiency anaemia may be helped by increasing the dietary intake of readily available iron and/or iron supplementation. If an increase in dietary intake is recommended, then additionally increasing the intake of Vitamin C may aid in the body's ability to absorb iron.

In anemia of chronic disease, anemia associated with chemotherapy, or anemia 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 anemia, a blood transfusion may be required.