It currently affects more than 3 million Americans and an estimated 1.62 billion people, globally.
It often results when other diseases interfere with the body's ability to produce healthy red blood cells or abnormally increase red blood cell breakdown or loss.
Here are some key points about anemia. More detail is in the main article.
- Anemia affects an estimated 24.8 percent of the world's population.
- Pre-school children have the highest risk, with an estimated 47 percent developing anemia, globally.
- More than 400 types of Anemia have been identified.
- Anemia is not restricted to humans and can affect cats and dogs.
There are many potential causes of anemia.
The most common symptom of all types of anemia is a feeling of fatigue and a lack of energy.
Other common symptoms may include:
- paleness of skin
- fast or irregular heartbeat
- shortness of breath
- chest pain
In mild cases, there may be few or no symptoms.
Some forms of anemia can have specific symptoms:
- Aplastic anemia: fever, frequent infections, and skin rashes
- Folic acid deficiency anemia: irritability, diarrhea, and a smooth tongue
- Hemolytic anemia: jaundice, dark colored urine, fever, and abdominal pains
- Sickle cell anemia: painful swelling of the feet and hands, fatigue, and jaundice
The body needs red blood cells to survive. They carry hemoglobin, a complex protein that contains iron molecules. These molecules carry oxygen from the lungs to the rest of the body.
Some diseases and conditions can result in a low level of red blood cells.
There are many types of anemia, and there is no single cause. It can sometimes be difficult to pinpoint the exact cause.
Below is a general overview of the common causes of the three main groups of anemia:
1) Anemia caused by blood loss
The most common type of anemia—iron deficiency anemia—often falls into this category. It is caused by a shortage of iron, most often through blood loss.
When the body loses blood, it reacts by pulling in water from tissues outside the bloodstream in an attempt to keep the blood vessels filled. This additional water dilutes the blood. As a result, the red blood cells are diluted.
Blood loss can be acute and rapid or chronic.
Rapid blood loss can include surgery, childbirth, trauma, or a ruptured blood vessel.
Chronic blood loss is more common in cases of anemia. It can result from a stomach ulcer, cancer, or tumor.
Causes of anemia due to blood loss include:
2) Anemia caused by decreased or faulty red blood cell production
Bone marrow is a soft, spongy tissue found in the center of bones. It is essential for the creation of red blood cells. Bone marrow produces stem cells, which develop into red blood cells, white blood cells, and platelets.
A number of diseases can affect bone marrow, including leukemia, where too many abnormal white blood cells are produced. This disrupts normal production of red blood cells.
Other anemias caused by decreased or faulty red blood cells include:
- Sickle cell anemia: Red blood cells are misshapen and break down abnormally quickly. The crescent-shaped blood cells can also get stuck in smaller blood vessels, causing pain.
- Iron-deficiency anemia: Too few red blood cells are produced because not enough iron is present in the body. This can be because of a poor diet, menstruation, frequent blood donation, endurance training, certain digestive conditions, such as Crohn's disease, surgical removal of part of the gut, and some foods.
- Bone marrow and stem cell problems: Aplastic anemia, for example, occurs when few or no stem cells are present. Thalassemia occurs when red blood cells cannot grow and mature properly.
- Vitamin deficiency anemia: Vitamin B-12 and folate are both essential for the production of red blood cells. If either is deficient, red blood cell production will be too low. Examples include megaloblastic anemia and pernicious anemia.
3) Anemia caused by the destruction of red blood cells
Red blood cells typically have a life span of 120 days in the bloodstream, but they can be destroyed or removed beforehand.
One type of anemia that falls into this category is autoimmune hemolytic anemia, where the body's immune system mistakenly identifies its own red blood cells as a foreign substance and attacks them.
Excessive hemolysis (red blood cell breakdown) can occur for many reasons, including:
- certain drugs, for example, some antibiotics
- snake or spider venom
- toxins produced through advanced kidney or liver disease
- an autoimmune attack, for instance, because of hemolytic disease
- severe hypertension
- vascular grafts and prosthetic heart valves
- clotting disorders
- enlargement of the spleen
There is a range of treatments for anemia. They all aim to increase the red blood cell count. This, in turn, increases the amount of oxygen the blood carries.
Treatment will depend on the type and cause of anemia.
- Iron deficiency anemia: Iron supplements or dietary changes. If the condition is due to loss of blood, the bleeding must be found and stopped.
- Vitamin deficiency anemias: Treatments include dietary supplements and B-12 shots.
- Thalassemia: Treatment includes folic acid supplementation, removal of the spleen, and, sometimes, blood transfusions and bone marrow transplants.
- Anemia of chronic disease: This is anemia associated with a serious, chronic underlying condition. There are no specific treatments, and the focus is on the underlying condition.
- Aplastic anemia: The patient will receive blood transfusions or bone marrow transplants.
- Sickle cell anemia: Treatment includes oxygen therapy, pain relief, and intravenous fluids. There may also be antibiotics, folic acid supplements, and blood transfusions. A cancer drug known as Droxia or Hydrea is also used.
- Hemolytic anemias: Patients should avoid medication that may make it worse and they may receive immunosuppressant drugs and treatment for infections. Plasmapheresis, or blood-filtering, might be necessary in some cases.
There are more than 400 types of Anemia currently known, and these are divided into three main groups according to their cause:
- Anemia caused by blood loss
- Anemia caused by decreased production or production of faulty red blood cells
- Anemia caused by the destruction of red blood cells
Types of anemia within these categories include:
If the anemia is caused by nutritional deficiencies, a change to an iron-rich diet can help alleviate the symptoms. The following foods are high in iron:
- iron-fortified cereals and breads
- dark-green leafy vegetables, for instance, curly kale and watercress
- pulses and beans
- brown rice
- white and red meats
- nuts and seeds
- dried fruits, including apricots, raisins, and prunes
Anemia can occur in people of all ages and race, both males and females. However, certain factors increase the risk.
- pregnancy and childbirth
- being born preterm
- being aged 1 to 2 years
- having a diet that is low in vitamins, mineral, and iron
- losing blood from surgery or injury
- long-term or serious illness, such as AIDs, diabetes, kidney disease, cancer, rheumatoid arthritis, heart failure, and liver disease
- family history of inherited anemias, such as sickle cell anemia
- intestinal disorders-affects absorption of nutrients
The outlook for a person with anemia depends on the cause. Many cases of anemia can be prevented or solved through a change in diet.
Some types can last for a long time, and some can be life-threatening without treatment.
Anyone who feels persistently weak and tired should see a doctor to check for anemia.
A complete blood count can help diagnose anemia.
There are different ways to diagnose anemia, but the most common is a blood test known as a complete blood count (CBC).
This measures a number of blood components, including hemoglobin and hematocrit levels, or the ratio of the volume of red blood cells to the total volume of blood.
A CBC can give an indication of the person's overall health and whether they have any conditions, such as leukemia or kidney disease.
If the red blood cell, hemoglobin, and hematocrit levels are all below "normal," then anemia is likely.
However, it does not provide a definitive diagnosis. It is possible to be outside the normal range but still healthy.
For other uses, see Anemia (disambiguation).
Anemia is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood, or a lowered ability of the blood to carry oxygen. When anemia comes on slowly, the symptoms are often vague and may include feeling tired, weakness, shortness of breath or a poor ability to exercise. Anemia that comes on quickly often has greater symptoms, which may include confusion, feeling like one is going to pass out, loss of consciousness, or increased thirst. Anemia must be significant before a person becomes noticeably pale. Additional symptoms may occur depending on the underlying cause.
The three main types of anemia are due to blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes of blood loss include trauma and gastrointestinal bleeding, among others. Causes of decreased production include iron deficiency, a lack of vitamin B12, thalassemia, and a number of neoplasms of the bone marrow. Causes of increased breakdown include a number of genetic conditions such as sickle cell anemia, infections like malaria, and certain autoimmune diseases. It can also be classified based on the size of red blood cells and amount of hemoglobin in each cell. If the cells are small, it is microcytic anemia. If they are large, it is macrocytic anemia while if they are normal sized, it is normocytic anemia. Diagnosis in men is based on a hemoglobin of less than 130 to 140 g/L (13 to 14 g/dL), while in women, it must be less than 120 to 130 g/L (12 to 13 g/dL). Further testing is then required to determine the cause.
Certain groups of individuals, such as pregnant women, benefit from the use of iron pills for prevention.Dietary supplementation, without determining the specific cause, is not recommended. The use of blood transfusions is typically based on a person's signs and symptoms. In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80 g/L (6 to 8 g/dL). These recommendations may also apply to some people with acute bleeding.Erythropoiesis-stimulating medications are only recommended in those with severe anemia.
Anemia is the most common blood disorder, affecting about a third of the global population.Iron-deficiency anemia affects nearly 1 billion people. In 2013, anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990. It is more common in women than men, during pregnancy, and in children and the elderly. Anemia increases costs of medical care and lowers a person's productivity through a decreased ability to work. The name is derived from Ancient Greek: ἀναιμίαanaimia, meaning "lack of blood", from ἀν- an-, "not" and αἷμα haima, "blood".
Signs and symptoms
Anemia goes undetected in many people and symptoms can be minor. The symptoms can be related to an underlying cause or the anemia itself. Most commonly, people with anemia report feelings of weakness or fatigue, and sometimes poor concentration. They may also report shortness of breath on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure. On examination, the signs exhibited may include pallor (paleskin, lining mucosa, conjunctiva and nail beds), but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or legulcers (seen in sickle-cell disease). In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiacventricular hypertrophy (enlargement). There may be signs of heart failure. Pica, the consumption of non-food items such as ice, but also paper, wax, or grass, and even hair or dirt, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin. Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome is more common in those with iron-deficiency anemia.
The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia eventually. Indeed, the most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency. (See Iron deficiency anemia)
- Disturbance of proliferation and maturation of erythroblasts
- Other mechanisms of impaired RBC production
Further information: Hemolytic anemia
Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These are generally featuring jaundice and elevated lactate dehydrogenase levels.[medical citation needed]
The roots of the words anemia and ischemia both refer to the basic idea of "lack of blood", but anemia and ischemia are not the same thing in modern medical terminology. The word anemia used alone implies widespreadeffects from blood that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-supplying ability (due to whatever type of hemoglobin or erythrocyte problem). In contrast, the word ischemia refers solely to the lack of blood (poor perfusion). Thus ischemia in a body part can cause localized anemic effects within those tissues.
Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia:
- General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space.
Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of hepcidin that leads to decreased access of iron to the circulation.
There are a number of definitions of anemia; reviews provide comparison and contrast of them. A strict but broad definition is an absolute decrease in red blood cell mass, however, a broader definition is a lowered ability of the blood to carry oxygen. An operational definition is a decrease in whole-blood hemoglobin concentration of more than 2 standard deviations below the mean of an age- and sex-matched reference range.
It is difficult to directly measure RBC mass, so the hematocrit (amount of RBCs) or the hemoglobin (Hb) in the blood are often used instead to indirectly estimate the value. Hemotocrit; however, is concentration dependent and is therefore not completely accurate. For example, during pregnancy a woman's RBC mass is normal but because of an increase in blood volume the hemoglobin and hematocrit are diluted and thus decreased. Another example would be bleeding where the RBC mass would decrease but the concentrations of hemoglobin and hematocrit initially remains normal until fluids shift from other areas of the body to the intravascular space.
The anemia is also classified by severity into mild (110 g/L to normal), moderate (80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adult males and adult non pregnant females. Different values are used in pregnancy and children.
Anemia is typically diagnosed on a complete 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 anemia. Examination of a stained blood smear using a microscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.[medical citation needed]
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. Some counters estimate hematocrit from direct measurements.[medical citation needed]
|Age or gender group||Hb threshold (g/dl)||Hb threshold (mmol/l)|
|Children (0.5–5.0 yrs)||11.0||6.8|
|Children (5–12 yrs)||11.5||7.1|
|Teens (12–15 yrs)||12.0||7.4|
|Women, non-pregnant (>15yrs)||12.0||7.4|
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 production of 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. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response. 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, such as: ESR, ferritin, serum iron, transferrin, RBC folate level, serum vitamin B12, hemoglobin electrophoresis, renal function tests (e.g. serum creatinine) although the tests will depend on the clinical hypothesis that is being investigated. When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded.[medical citation needed]
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 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. Limitations of MCV include cases where the underlying cause is due to a combination of factors – such as iron deficiency (a cause of microcytosis) and vitamin B12 deficiency (a cause of macrocytosis) where the net result can be normocytic cells.[medical citation needed]
Production vs. destruction or loss
The "kinetic" approach to anemia yields arguably 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 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 guaiac-positive stool, radiographic findings, or frank bleeding.[medical citation needed] The following is a simplified schematic of this approach:[medical citation needed]
*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. Here is a schematic representation of how to consider anemia with MCV as the starting point:
|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)|
|Macrocytic anemia (MCV>100)|
|Normocytic anemia (MCV 80–100)|
|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.
Main article: Microcytic anemia
Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:
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 due to insufficient dietary intake or absorption of iron to meet the body's needs. Infants, toddlers, and pregnant women have higher than average needs. Increased iron intake is also needed to offset blood losses due to digestive tract issues, frequent blood donations, or heavy menstrual periods. 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, 12% of all women of childbearing age have iron deficiency, compared with only 2% of adult men. The incidence is as high as 20% among African American and Mexican American women. Studies have shown iron deficiency without anemia causes poor school performance and lower IQ in teenage girls, although this may be due to socioeconomic factors. Iron deficiency is the most prevalent deficiency state on a worldwide basis. It is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular stomatitis).
- In the United States, the most common cause of iron deficiency is bleeding or blood loss, usually from the gastrointestinal tract. Fecal occult blood testing, upper endoscopy and lower endoscopy should be performed to identify bleeding lesions. In older men and women, the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyps or colorectal cancer.
- Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookworms, amebiasis, schistosomiasis and whipworms).
The Mentzer index (mean cell volume divided by the RBC count) predicts whether microcytic anemia may be due to iron deficiency or thallasemia, although it requires confirmation.
Main article: Macrocytic anemia
- Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid, or both. Deficiency in folate 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.
- Pernicious anemia is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12.
- Macrocytic anemia can also be caused by removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vitamin B12/folate absorption. Therefore, one must always be aware of anemia following this procedure.
- Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of liver disease can also cause macrocytosis.
- Drugs such as methotrexate, zidovudine, and other substances may inhibit DNA replication such as heavy metals
Macrocytic anemia can be further divided into "megaloblastic anemia" or "nonmegaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (six to 10 lobes). The nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired DNA globin synthesis,) which occur, for example, in alcoholism. In addition to the nonspecific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology. Other features may include a smooth, red tongue and glossitis. The treatment for vitamin B12-deficient anemia 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 isolate the curative substance chemically and ultimately were able to isolate the vitamin B12 from the liver. All three shared the 1934 Nobel Prize in Medicine.
Main article: Normocytic anemia
Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size (mean corpuscular volume) remains normal. Causes include:
A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs. A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia.
Heinz body anemia
Heinz bodies form in the cytoplasm of RBCs and appear as small dark dots under the microscope. In animals, Heinz body anemia has many causes. It may be drug-induced, for example in cats and dogs by acetaminophen (paracetamol), or may be caused by eating various plants or other substances:
Hyperanemia is a severe form of anemia, in which the hematocrit is below 10%.
Refractory anemia, an anemia which does not respond to treatment, is often seen secondary to myelodysplastic syndromes.Iron deficiency anemia may also be refractory as a clinical manifestation of gastrointestinal problems which disrupt iron absorption or cause occult bleeding. 
Treatments for anemia depend on cause and severity. Vitamin supplements given orally (folic acid or vitamin B12) or intramuscularly (vitamin B12) will replace specific deficiencies.[medical citation needed]