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This article waslast modified on 6 October 2023.
Overview

Anaemia is a condition in which the number of red blood cells (RBC) or the haemoglobin (Hb) concentration within them is lower than normal. It mainly affects women and children. Anaemia occurs when there isn’t enough Hb in the body to carry oxygen to the organs and tissues. In severe cases, anaemia can cause poor development in children. It can also cause problems for pregnant women and their babies. Anaemia is quite often preventable and treatable.

Anaemia is diagnosed based on Hb concentrations falling below specified levels based on age, sex, and physiological status. It is considered a symptom of an underlying condition(s). The causes of anaemia can be acquired or inherited. ‘Acquired’ means you aren’t born with the condition, but you develop it. ‘Inherited’ means your parents passed the gene(s) for the condition on to you. Sometimes the cause of anaemia is unknown.

Anaemia may be caused by several factors: nutrient deficiencies, inadequate diet (or the inadequate absorption of nutrients), infections, inflammation, chronic diseases, gynaecological and obstetric conditions, and inherited RBC disorders.

Iron deficiency is considered the most common nutritional deficiency leading to anaemia. Deficiencies in vitamin A, folate, vitamin B12 and riboflavin (vitamin B2) can also result in anaemia due to their specific roles in the synthesis of Hb and/or RBC production. Additional mechanisms include nutrient losses (e.g., blood loss from intestinal bleeding, haemorrhage associated with childbirth, or menstrual loss), impaired absorption, low iron stores at birth, and nutrient interactions affecting iron availability.

Infections can be another important cause of anaemia. Infections can impair nutrient absorption and metabolism or can cause nutrient loss. Many different chronic conditions can cause inflammation and lead to anaemia of inflammation or anaemia of chronic disease.

Consistent heavy menstrual losses, maternal blood volume expansion during pregnancy, and blood loss during and after childbirth, particularly in cases of postpartum haemorrhage, commonly lead to anaemia.

Additionally, in some parts of the world, inherited red blood cell disorders are a common cause of anaemia. These include conditions such as α- and β-thalassemia due to abnormalities of Hb synthesis, sickle cell disorders due to changes in the Hb structure, other haemoglobinopathies due to Hb gene variants, abnormalities of RBC enzymes, or abnormalities of the RBC membrane.

Signs and Symptoms

Common and non-specific symptoms of anaemia include:

  • tiredness
  • dizziness or feeling light-headed
  • cold hands and feet
  • headache
  • shortness of breath, especially upon exertion

Severe anaemia can cause more serious symptoms including:

  • pale mucous membranes (in the mouth, nose etc.)
  • pale skin and under the fingernails
  • rapid breathing and heart rate
  • dizziness when standing up
  • bruising more easily

Initial Laboratory Tests

Full Blood Count (FBC)
Anaemia may first be detected when a full blood count (FBC) is done as part of a health check or during investigations for another illness. FBC is a routine test that counts the number of each of the different types of cells in your blood. It gives your doctor information about the size, shape, and relative maturity of the blood cells present in your blood at that moment.

Blood Film
If results of the FBC indicate anaemia, it may be followed up with an examination of a blood film. Results from this may give clues to the cause of the anaemia. Several other tests can help discover the cause of the anaemia and then guide treatment. See the individual discussions of the different types of anaemia for more on these.

Accordion Title
About Anaemia
  • Iron Deficiency Anaemia

    Iron deficiency anaemia is the most common cause of anaemia. Symptoms are related to the overall decrease in number of RBC and/or Hb.

    Symptoms that are typical of iron deficiency and may include brittle or spoon-shaped nails, swollen or sore tongue, cracks or ulcers at the corners of the mouth (“angular cheilosis”) or a craving to eat unusual non-food substances such as ice or dirt (also known as “pica”).

    Iron is an essential trace element and is necessary to produce healthy RBC. It is one component of haem, a part of Hb, the protein in RBC that binds to oxygen and enables RBC to transport oxygen throughout the body. If not enough iron is absorbed by the body, then iron that is stored in the body will be used up. If iron stores are low then fewer RBC are made and they have decreased amounts of Hb in them which results in anaemia.

    Some of the causes of iron deficiency include:

    • Bleeding—if bleeding is excessive or occurs over a period of the time (chronic), the body may not take in enough iron or have enough stored to produce sufficient Hb and/or RBC to replace what is lost. In women, iron deficiency may be due to heavy menstrual periods, but in older women and in men, the bleeding is often from disease of the stomach or intestines such as ulcers and cancer.
    • Dietary deficiency—iron deficiency may be due simply to not eating enough iron in the diet. In children and pregnant women especially, the body needs more iron, Pregnant and nursing women frequently develop this deficiency since the baby requires large amounts of iron for growth. Lack of iron can lead to low-birth-weight babies and premature delivery. Pre-pregnant and pregnant women are routinely given iron supplements to prevent these complications. Babies who are taking milk from anaemic mothers tend to have iron deficiency anaemia as well.
    • Absorption problem—certain conditions affect the absorption of iron from food in the gastrointestinal (GI) tract and over time can result in anaemia. These include, for example, Coeliac disease, Crohn disease, lack of acid in the stomach (“achlorhydria”) or previous surgery to remove part of the bowel.

    Laboratory Tests

    Initial blood tests typically include a full blood count (FBC). Results may show:

    • Hb—may be normal early in the disease but will fall as the anaemia worsens.
    • Red blood cell indices—early on, the RBC may have a normal size (MCV) and Hb concentration (MCH), but as the anaemia progresses, these will reduce.

    A blood film may reveal RBC that are smaller and paler than normal as well as RBC that vary in size (anisocytosis) and shape (poikilocytosis). Abnormally shaped RBC may include target cells and pencil cells. The blood film may also give clues to causes of inflammation. For example, it might show signs of an underactive spleen, which can be due with Coeliac disease, in which iron is sometimes not absorbed well.

    If your doctor suspects that your anaemia is due to iron deficiency, they may request several additional tests to confirm the iron deficiency. These may include:

    • Serum iron—the level of iron in your blood; the result is usually decreased. It is important that patients fast before a serum iron blood test or the result may be misleadingly high.
    • Ferritin—reflects the amount of stored iron in your body and is usually low in anaemia. Ferritin is a good marker of iron deficiency anaemia, unless infection or inflammation are present when it can be falsely raised.
    • Measurement of plasma transferrin levels is useful in the differential diagnosis of anaemia and will rise with iron deficiency anaemia.
    • Reticulocytes – measuring the Hb content of the reticulocytes (immature RBC) as a direct assessment of the iron used to produce Hb. This is now considered to be a very sensitive marker of iron deficiency.

    Some blood tests for iron may be influenced by other illnesses or factors and they should be interpreted with caution. Sometimes they clearly indicate iron deficiency, sometimes they are unclear and sometimes they can be misleading and unhelpful.

    If the iron deficiency is thought to be due to abnormal blood loss, such as chronic bleeding from the intestine, then other tests and procedures may be performed including a referral for colonoscopy to look and see if blood is being lost into the intestine.

    A test for Helicobacter pylori may detect a bacterium that can cause ulcers in the GI tract which may be a cause of chronic bleeding. Blood tests showing antibodies to Helicobacter may be misleading however and examination of the faeces for the bacterium (faecal Helicobacter antigen testing) may be used instead.

    If any of these tests are positive or if it is strongly suspected a GI bleed exists, then procedures such as endoscopy or colonoscopy may be done to find the location of the bleeding so that it can be treated.

    Treatment of iron deficiency typically involves iron supplements. These are usually given by mouth. In those intolerant of iron supplements or who cannot absorb iron, iron can be replaced by using an intravenous infusion. If iron-deficiency is suspected to be due to abnormal blood loss, further testing is often required to determine the reason for the bleeding. When the underlying cause is found and treated then the anaemia usually resolves.

    Some forms of haemolytic anaemia (when RBC are being destroyed in the body) can lead to iron deficiency.

  • Pernicious anaemia and other B vitamin deficiencies

    Vitamin B12 is found only in animal foods including meat, dairy and egg products. Very strict vegans require vitamin B12 supplements to remain healthy.

    Pernicious anaemia is a condition in which the body does not make enough of a substance called intrinsic factor. Intrinsic factor is a protein produced by parietal cells in the stomach. It binds to vitamin B12 and allows it to be absorbed from the small intestine. Vitamin B12 is important in the production of RBC. Without enough intrinsic factor, the body cannot absorb vitamin B12 from the diet and cannot produce enough normal RBC, leading to anaemia.

    Other causes of vitamin B12 deficiency and anaemia include conditions that affect absorption of the vitamin from the small intestine such as surgery, certain drugs, digestive disorders (Coeliac disease, Crohn’s disease) and infections.

    Vitamin B12 deficiency can result in general symptoms of anaemia as well as nerve problems such as numbness and tingling that starts first in the hands and feet.

    Additional symptoms may include muscle weakness, slow reflexes, loss of balance and unsteady walking. Severe cases can lead to confusion, memory loss, depression and/or dementia.

    Folic acid is the synthetic version of the vitamin folate, also known as vitamin B9. Folic acid is found in many foods, especially in green, leafy vegetables. Some breakfast cereals are fortified with folic acid. Folic acid is needed during pregnancy for normal development of the baby’s brain and spinal cord. It is important for women considering pregnancy to take folate supplements before they get pregnant and during pregnancy to make sure they are not folate deficient. Folate deficiency early in pregnancy can cause problems in the development of the brain and spinal cord of the baby (e.g. “spina bifida”).

    Anaemias resulting from vitamin B12 or folate deficiency are sometimes referred to as macrocytic anaemia because RBC are larger than normal, or “megaloblastic” due to abnormally large immature red cells in the bone marrow. A lack of these vitamins does not allow RBC to grow and then divide as they normally would during development which leads to their large size. This leads to a reduced number of abnormally large RBC and anaemia.

    Laboratory Tests
    Symptoms of anaemia will usually be investigated initially with a full blood count (FBC). In pernicious anaemia or vitamin B12/folate deficiency, these usually show:

    • A low Hb
    • The mean corpuscular volume (MCV), which is the average size of RBC, is often high

    A blood film will reveal RBC that are abnormally large, abnormally shaped, and sometimes occasional giant white blood cells.

    If the cause of your anaemia is thought to be due to pernicious anaemia or dietary deficiency of B12 or folate, additional tests are usually requested to make the diagnosis. Some of these include:

    Treatment in these conditions involves supplementation with the vitamin that is deficient. Vitamin B12 is usually given by injection, typically every 3 months , although tablets can sometimes be given. Treatment of underlying causes such as a digestive disorder or infection may help to resolve the anaemia.

    For more on this, see the article on Vitamin B12 and Folate Deficiency

  • Aplastic Anaemias

    Aplastic anaemia is a rare disease, caused by a decrease in the number of all types of blood cells produced by the bone marrow. Normally, the bone marrow produces a sufficient number of RBC, white blood cells (WBC) and platelets for normal body function. If the bone marrow is not able to produce enough blood cells to replace those that die, a number of symptoms, including those due to anaemia, may result.

    Symptoms of aplastic anaemia can appear abruptly or can develop more slowly.

    Some additional signs and symptoms that occur with aplastic anaemia include those due to decreased platelets:

    • Prolonged bleeding
    • Frequent nosebleeds
    • Bleeding gums
    • Easy bruising

    and due to a low WBC count:

    • Increased number and severity of infections.

    Causes of aplastic anaemia usually have to do with damage to the stem cells in the bone marrow that are responsible for blood cell production. Most often, no obvious underlying cause is found and this is labelled idiopathic aplastic anaemia. Sometimes, specific factors that may be involved with bone marrow damage and that can lead to aplastic anaemia are identified and include:

    Rarely, aplastic anaemia is due to an inherited (genetic) disorder such as Fanconi anaemia. (For more on this condition, see the Fanconi Anemia Research web site

    Laboratory Tests
    The full blood count (FBC), may reveal many abnormal results.

    • Hb may be low
    • RBC and WBC counts are low
    • Platelet count is low
    • The MCV (average red cell size) may be normal or slightly raised
    • The differential white blood count shows a decrease in most types of cells but not lymphocytes.


    Some additional tests that may be performed to help discover the type and cause of anaemia include:

    • Reticulocyte count -result is usually low
    • Erythropoietin - usually increased in aplastic anaemia
    • A bone marrow aspiration and trephine biopsy will show a decrease in the number of all types of mature cells.
    • Tests for infections such as hepatitis, EBV, CMV help to discover the cause
    • Test for arsenic (a heavy metal) and other toxins
    • Iron tests or tests for vitamin B12 may be done to rule out other causes
    • Antibody tests such as ANA to find out if the cause is autoimmune disease

    A physical examination or complete medical history may reveal possible causes for aplastic anaemia such as exposure to toxins or certain drugs (for example, chloramphenicol) or prior treatment for cancer.

    Some cases of aplastic anaemia are temporary while others have lasting damage to the bone marrow. Treatment depends on the cause. Reducing or eliminating exposure to certain toxins or drugs may help resolve the condition. Medications may be given to stimulate bone marrow production, to treat infections or to suppress the immune system in cases of autoimmune disorders. Blood transfusions and a bone marrow transplant may be needed in severe cases.

    Pure red cell aplasia is a disease with some similarities to aplastic anaemia, except only the red blood cell precursors are absent. This can also occur with cancers (especially of the thymus gland) and autoimmune conditions. Infection with parvovirus B19 can cause temporary pure red cell aplasia.

  • Haemolytic Anaemias

    Sometimes, anaemia is due to problems that cause the red blood cells (RBC) to die or be destroyed early in their life. Normally, red cells live in the blood for about 4 months. In haemolytic anaemia, this time is shortened, sometimes to only a few days. The bone marrow is not able to produce new RBC quickly enough to replace those that have been destroyed leading to a decreased number of RBC in the blood which in turn leads to a reduced ability to carry oxygen to all parts of the body. This results in the typical symptoms of anaemia.

    Depending on its cause, haemolytic anaemia can be chronic, developing and lasting over a long period or lifetime, or may be acute, occurring very rapidly with the development of serious signs and symptoms. The various forms of haemolytic anaemia can have a wide range of signs and symptoms.

    The different causes of haemolytic anaemia fall into two main categories:

    • Inherited forms in which a gene or genes are passed from one generation to the next and result in abnormal RBC or Hb
    • Acquired forms in which something other than inherited disease results in the early destruction of RBC

    Anaemias due to abnormal Haemoglobin structure - sometimes called haemoglobinopathies

    Sickle cell anaemia, due to production of an abnormal form of haemoglobin called HbS, usually causes no difficulties in people with the “trait” (when you carry only one mutated gene from one of your parents), but severe clinical problems as the “disease” (when you carry two mutated genes, one from each of your parents). The red blood cells are misshapen, unstable (leading to haemolysis) and can block blood vessels, causing pain and anaemia. Screening is usually done on newborns – particularly those of African descent. Sometimes screening is done prenatally on a sample of amniotic fluid. Follow up tests for haemoglobin variants may be performed to confirm a diagnosis. Treatment is usually based on the type, frequency and severity of symptoms.

    There are many other abnormal haemoglobins than sickle disease, often extremely rare e.g. HbC, HbD, HbE

    Thalassaemia is the name for a group of inherited conditions that affect Hb production. People with thalassaemia produce either no or too little Hb, which is used by red blood cells to carry oxygen around the body. This can make them very anaemic.

    It mainly affects people of Mediterranean, south Asian, southeast Asian and Middle Eastern origin. There are different types of thalassaemia, which can be divided into alpha and beta thalassaemias. Beta thalassaemia major is the most severe type. Other types include beta thalassaemia intermedia, alpha thalassaemia major and haemoglobin H disease.

    Thalassaemia is caused by faulty genes that affect the production of Hb. A child can only be born with thalassaemia if they inherit these faulty genes from both parents. For example, if both parents have the faulty gene that causes beta thalassaemia major, there is a 1 in 4 chance of each child they have being born with the condition. The parents of a child with thalassaemia are usually carriers (also known as thalassaemia trait). This means they have some faulty genes, and some normal genes. Being a thalassaemia carrier will not generally cause you any health problems, but you're at risk of having children with thalassaemia.

    Other less common types of inherited forms of haemolytic anaemia include:

    • Hereditary spherocytosis—a weakness in the RBC membrane caused by a genetic defect which results in abnormally shaped small dark rounded RBC which may be seen on a blood film. These RBC have a shortened lifespan and the patient can become anaemic.
    • Hereditary elliptocytosis—another red cell wall defect causing abnormally cigar-shaped RBC seen on a blood film
    • Glucose-6-phospate dehydrogenase (G6PD) deficiency—G6PD is an enzyme that is necessary for RBC survival. Its deficiency may be diagnosed with a test for its activity
    • Pyruvate kinase deficiency—Pyruvate kinase is another enzyme important for RBC survival and its deficiency may also be diagnosed with a test for its activity.

    Laboratory Tests
    Since some of these inherited forms may have mild symptoms, they may first be detected on a routine FBC and blood film which can reveal various abnormal results that give clues as to the cause. Follow up tests are then usually performed to make a diagnosis. Some of these include:

    • Tests for haemoglobin variants such as Hb electrophoresis
    • DNA analysis—not routinely done but can be used to help diagnose haemoglobin variants, thalassaemia, and to determine carrier status.
    • G6PD test—to detect deficiency in this enzyme
    • EMA binding test—detects RBC that are more fragile than normal which may be found in hereditary spherocytosis

    These genetic disorders cannot be cured but often the symptoms resulting from the anaemia can be reduced by treatment. Sometimes these disorders may have implications for planned pregnancies, especially if both partners have abnormal types of haemoglobin, and specialist advice and sometimes further investigations may be helpful in assessing risks for future babies.

    Acquired Haemolytic Anaemia
    Some of the conditions or factors involved in acquired forms of haemolytic anaemia include:

    • Autoimmune haemolytic anaemia (AIHA) or cold agglutinin disease (CAD)—conditions in which the body produces antibodies against its own red blood cells.
    • Transfusion reaction—result of blood donor-recipient incompatibility. This occurs very rarely but when it does can have some serious complications.
    • Mother-baby blood group incompatibility (especially rhesus antigen incompatibility where mothers are Rhesus-negative)—may result in haemolytic disease of the newborn.
    • Drugs—certain drugs such as penicillin can trigger the body into producing antibodies directed against RBC or cause the direct destruction of RBC. Other drugs, such as some antimalarial drugs and some anaesthetics can cause destruction of red cells in susceptible individuals with G6PD deficiency or some forms of abnormal haemoglobin.
    • Physical destruction of RBC by, for example, an artificial heart valve or cardiac bypass machine used during open-heart surgery
    • Paroxysmal Nocturnal Haemoglobinurina (PNH)—a rare condition in which the different types of blood cells including RBC, WBCs and platelets may be abnormal. Because the RBC are defective they are susceptible to destruction by the body’s immune system. As the name suggests, people with this disorder can have acute, recurring episodes in which many RBC are destroyed. This disease occurs due to a change or mutation in a gene called PIGA in the stem cells that make blood. Though it is a genetic disorder, it is not passed from one generation to the next (it is not an inherited condition). Patients will often pass dark urine due to the haemoglobin released by destroyed RBC being cleared from the body by the kidneys. This is most noticeable first thing in the morning when urine is most concentrated. Episodes are thought to be brought on when the body is under stress during illnesses or after physical exertion. (For more on this, see the Genetic Home Reference webpage.)

    These types of haemolytic anaemias are often first identified from signs and symptoms see during physical examination and after taking a medical history. A medical history can reveal, for example, a recent transfusion, treatment with penicillin or cardiac surgery. A FBC and/or blood film may show various abnormal results. Depending on those findings, additional follow up tests may be performed. Some of these may include:

    • Tests for autoantibodies for suspected autoimmune disorders
    • Direct antiglobulin test (DAT) (formerly known as a “Coombs’ test”) in the case of transfusion reaction, mother-baby blood type incompatibility, or autoimmune haemolytic anaemia
    • Haptoglobin – this protein mops up free Hb in the blood for recycling after blood cells are haemolysed and may be reduced in the blood during periods of haemolysis.
    • Reticulocyte count – reticulocytes are young RBC and an increase reflects increased production of red cells in the bone marrow to keep up with haemolysis.

    Treatment for haemolytic anaemia depends on the cause. In general, the goals are the same: to treat the underlying cause of the anaemia, to decrease or stop the destruction of RBC and to increase the Hb to alleviate symptoms. This may involve, for example:

    • Drugs that suppress the immune system and decrease production of autoantibodies that destroy RBC
    • Blood transfusions to increase number of healthy RBC
    • Bone marrow transplant—to increase production of normal RBC
    • Avoiding triggers that cause the anaemia such as the cold in some forms of autoimmune haemolytic anaemia or fava beans and certain drugs for those with G6PD deficiency
  • Anaemia Caused by Chronic Diseases

    Chronic (long term) illnesses can cause anaemia. Often, anaemia caused by chronic diseases goes undetected until a routine test such as a full blood count reveals abnormal results. Several follow-up tests may be used to discover the underlying cause. The anaemia in these cases is generally caused inflammation causing too much or too little production of various substances and resultant suppression of the normal function of the bone marrow. There are many chronic conditions and diseases that can result in anaemia. Some examples of these include:

    • Kidney disease—RBC are produced by the bone marrow in response to a hormone called erythropoietin (EPO), made primarily by the kidneys. Chronic kidney disease can cause anaemia resulting from too little production of this hormone; the anaemia can be treated by giving erythropoietin injections.
    • Inflammatory conditions—Whenever there are chronic diseases that stimulate the body’s inflammatory system, the ability of the bone marrow to respond to erythropoietin is reduced. For example, rheumatoid arthritis (a severe form of joint disease caused by the body attacking its own joints, termed an autoimmune disease) can cause anaemia by reducing the effectiveness of erythropoietin on bone marrow.
    • Other diseases that can produce anaemia in the same way as inflammatory conditions include chronic infections (such as with HIV or tuberculosis), cancer, and cirrhosis.

    A number of additional tests may be requested after initial tests (FBC and blood film) have been found to be abnormal. These will help discover the underlying cause of chronic anaemia. Some of these may include:

    Treatment of anaemia due to chronic conditions usually involves determining and/or resolving the underlying disease. Blood transfusions may be used to treat the condition in the short term. Erythropoietic stimulating agents such as synthetic versions of EPO are widely used in patients with chronic kidney diseases.