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Haemolytic anaemias

Rarely, anaemia is due to problems that cause the red blood cells (RBCs) to die or be destroyed prematurely. 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 RBCs quickly enough to replace those that have been destroyed, leading to a decreased number of RBCs in the blood, which in turn leads to a diminished capacity to supply oxygen to tissues throughout the body. This results in the typical symptoms of anaemia including:

  • weakness and/or fatigue
  • lack of energy

Depending on the cause, different forms of haemolytic anaemia can be chronic, developing and lasting over a long period or lifetime, or may be acute. The various forms can have a wide range of signs and symptoms. See the discussions of the various types below for more on this.

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 that result in abnormal RBCs or haemoglobin
  • Acquired forms in which some factor other than inherited results in the early destruction of RBCs
Inherited haemolytic anaemia

Two of the most common causes of inherited haemolytic anaemia are sickle cell anaemia and thalassaemia:

Sickle cell anaemia can cause minor difficulties as the ‘trait’ (when you carry 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.

Thalassemia is a hereditary abnormality of haemoglobin production and results in small red blood cells that resemble those seen in iron deficiency. In its most severe form, the red cells have a shortened life span. In milder forms, anaemia is usually mild or absent, and the disease may be detected by finding small blood cells on a routine FBC. This genetic disease is found frequently in people of Mediterranean, African and Asian heritage. The defect in production may involve one of two components of haemoglobin called the alpha and beta protein chains. The disease is defined as alpha thalassaemia or beta thalassaemia accordingly. The "beta minor" form (sometimes called beta thal trait, as with sickle cell) occurs when a person inherits half normal genes and half beta thalassemia genes. It causes a mild anaemia and no symptoms. The "beta major" form (due to inheriting two beta thalassaemia genes and also called Cooley’s anaemia) is more severe and may result in growth problems, jaundice, and severe anaemia.

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

  • Hereditary spherocytosis — results in abnormally shaped RBCs that may be seen on a blood smear
  • Hereditary elliptocytosis — another cause of abnormally shaped RBCs seen on a blood film examination
  • 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 examination, 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 haemoglobin 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
  • Flow cytometry detection of abnormal or missing red cell membrane proteins — detects RBCs 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 may be alleviated with treatment as necessary.

Acquired haemolytic anaemia

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

  • Autoimmune disorders — a condition in which the body produces antibodies against its own red blood cells. It is not understood why this may happen.
  • Transfusion reaction — result of blood donor-recipient incompatibility. This occurs very rarely but when it does, it can have some serious complications. For more on this, see the Blood banking article.
  • Mother-baby blood group incompatibility — may result in haemolytic disease of the newborn.
  • Drugs — certain drugs such as penicillin can trigger the body to produce antibodies directed against RBCs or cause the direct destruction of RBCs.
  • Physical destruction of RBCs 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 RBCs, WBCs and platelets are abnormal. Because the RBCs are defective, they are destroyed by the body earlier than the normal lifespan. As the name suggests, people with this disorder can have acute, recurring episodes in which many RBCs 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 RBCs 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 by signs and symptoms, during physical examination and by 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:

Treatments for haemolytic anaemia are as varied as the causes. However, the goals are the same: to treat the underlying cause of the anaemia, to decrease or stop the destruction of RBCs, and to increase the RBC count and/or haemoglobin level to alleviate symptoms. This may involve, for example:

  • Drugs used to decrease production of autoantibodies that destroy RBCs
  • Blood transfusions to increase the number of healthy RBCs
  • Bone marrow transplant — to increase production of normal RBCs
  • Avoiding triggers that cause the anaemia such as the cold in some forms of autoimmune haemolytic anaemia or fava beans for those with G6PD deficiency.

Last Review Date: November 1, 2019