Haemolytic Anaemia

What Is Haemolytic Anaemia?

This is an uncommon type of anaemia in which destruction of red blood cells occurs before their typical lifetime is reached. Red blood cells in good physical shape should live for around 120 days before they are removed from the body. However, those with haemolytic anaemia find that red blood cells are broken down before this period of time, which means that the cells are brought to the end of their lives before they can be replaced with new ones (known as haemolysis).

About anaemia

Haemoglobin is a protein rich in iron and responsible for carrying oxygen around the body. It also gives red blood cells their colour. Anaemia is a common condition and is brought on when the body carries an insufficient quantity of red blood cells or deficient haemoglobin. Anaemia is sometimes referred to as a low blood count.

One of the main indications of anaemia is extreme tiredness and fatigue, which develop due to tissues in the body not getting enough oxygen. In people with anaemia there is a shortage of oxygen travelling in the bloodstream. This is because of a lack of haemoglobin or a decreased proportion of red blood cells. If the tissues do not receive enough oxygen they may not be able to function as effectively as normal.

Red blood cells are also known as erythrocytes; they are usually a similar size and shaped like doughnuts without the hole in the centre. Such cells in good health normally survive in the body for around 120 days before they are taken out of the body. The iron is taken from old red blood cells and recycled to produce new red blood cells. These are produced on a continual basis by the bone marrow to replace those that are departed from the bloodstream.

Blood contains other forms of blood cells; these include white blood cells (responsible for combating infections and illnesses) and platelets (form an important part of the blood clotting process). In some forms of anaemia the levels of all these blood cell is lower than normal.

Three major sources of anaemia are apparent, which include blood loss, accelerated break down of red blood cells and reduced red blood cell manufacture.

Haemolytic anaemia

Haemolytic anaemia is brought on by the accelerated damage of red blood cells, which is when they are broken up before completion of their 120 day lifespan. When red blood cells become damaged this in turn means that the body is unable to produce a sufficient amount to substitute those destroyed. This is despite increased cell production by the bone marrow.

The body can also produce irregular red blood cells that are broken down. Also, the cells can become damaged due to infections, taking certain types of medication and the body’s immune response. Haemolysis (the process of breaking down red blood cells) can become apparent in the bloodstream or the spleen.  

There are two core classes of haemolytic anaemia: acquired and inherited. Inherited haemolytic anaemia is passed on to child from parent, while acquired haemolytic anaemia is brought on by other factors, such as infection or an abnormal response of the immune system. Haemolytic anaemia can develop gradually or happen suddenly. It affects people in different ways being that there are mild, moderate and severe forms of the condition.

Outlook

The condition can be controlled effectively and mild cases may not require any action at all. But severe cases can be serious and even dangerous if not properly treated. People with inherited haemolytic anaemia have the condition for life and must receive ongoing treatment. Acquired haemolytic anaemia can usually be dealt with by treating the cause (for example, an infection).

Types of haemolytic anaemia

There are various forms of the condition, some of which are inherited and others acquired.

Inherited haemolytic anaemia types

Where inherited haemolytic anaemia is apparent one or more genes which manage red blood cell manufacture are defective, and this causes abnormal cell manufacture in the bone marrow. There are various possible abnormalities that can affect the outer surface membrane of the cell, the chemical make-up of the cell and the production of haemoglobin. Irregular cells may be more fragile than healthy cells, leading them to break up in the bloodstream. The immune system may also identify the red blood cells as abnormal, and the spleen may break them down and remove them.

Sickle cell anaemia

In such cases of sickle cell anaemia, haemoglobin carried in the red blood cells is abnormal, which leads to the blood cells becoming an irregular shape. Sickle cell anaemia is so-called because the cells are shaped like sickles. Sickle cells die before the usual lifespan and are expelled from the body. It is most prevalent in people of African American heritage.

Thalassaemia

Thalassaemia is an umbrella term for a collection of anaemic conditions. These occur when the body does not produce sufficient kinds of haemoglobin and causes irregular red blood cells to be produced, die prematurely and be taken out of the body. Thalassaemia is mainly prevalent amongst individuals of Mediterranean, Asian and African ancestry.

Hereditary spherocytosis

This is where the membrane of the red blood cells is abnormal, causing the cells to become spherical in shape. The spherical cells have a shorter lifespan than typical red blood cells, and are extracted from the bloodstream too early. Hereditary spherocytosis is mainly found amongst people of Northern European heritage.

Hereditary elliptocytosis

Hereditary elliptocytosis, also recognised as ovalocytosis, affects the cell membranes of the red blood cells. In such cases the cells are oval-shaped (elliptical). Elliptical cells are not as supple as fitter red blood cells and they may not live as long.

Glucose-6 phosphate dehydrogenase deficiency (G6PD)

In such cases red blood cells do not have a vital enzyme recognised as G6PD. This means that when the blood cells encounter specific substances (such as medication) in the blood, they can rupture and break down. This class of haemolytic anaemia is most prevalent amongst African American and Mediterranean men.

Pyruvate kinase deficiency

This class of haemolytic anaemia happens if red blood cells are absent of an enzyme identified as pyruvate kinase. Without pyruvate kinase the cells are more inclined to break up and die prematurely.

Acquired categories of haemolytic anaemia

This is when red blood cells are sometimes broken down even if they are healthy. This may be caused by a range of factors, including infection or disease. In most cases the damage occurs in the bloodstream or the spleen (this is more common). Three main forms of acquired haemolytic anaemia exist, which are alloimmune, autoimmune and drug-induced.

Autoimmune haemolytic anaemia (AIHA): people who have autoimmune haemolytic anaemia produce antibodies in opposition to their own red blood cells. This category of haemolytic anaemia affects around half of those with the condition and tends to be found in those over the age of forty. It can be serious if not properly treated.

Certain conditions and diseases can increase the risk of an individual developing haemolytic anaemia. These consist of chronic lymphocytic leukaemia, Hodgkin’s lymphoma, other cancers of the blood, Epstein-Barr viral infections, hepatitis, mycoplasma pneumonia and infections caused by the cytomegalovirus. AIHA can develop quickly and may potentially be severe.

With AIHA the body may also produce antibodies known as warm antibodies, which means that the antibodies damage red blood cells at high temperatures. In other cases the body manufactures cold antibodies, which is when the antibodies damage red blood cells at cold temperatures (below 0-10 degrees Celsius). Warm-reactive AIHA is more widespread than cold-reactive AIHA.

Alloimmune haemolytic anaemia: this class of haemolytic anaemia develops in reaction to a blood transfusion. The body produces antibodies in response to the donor blood, which can occur if the donor blood is not the same blood type as the individual’s. A pregnant female can also produce Alloimmune antibodies when her blood type is negative and her baby’s blood type is positive. If this is the case medication called RhoGam is given when the baby is born, to prevent the mother’s body from producing antibodies in opposition to the baby’s type of blood.

Drug-induced haemolytic anaemia: some types of drug can cause an adverse reaction which contributes to haemolytic anaemia, including high amounts of penicillin and similar associated drugs, such as quinine, anti-malaria drugs, anti-inflammatory medications and acetaminophen.

Mechanical haemolytic anaemia

Physical harm to the membranes of red blood cells can be brought on due to microangiopathic changes in the blood vessels. Artificial heart valves or devices can also damage the red blood cells, as can damage brought about by surgery to the heart and eclampsia or pre-eclampsia (high blood pressure during the latter stages of pregnancy). Strenuous physical activity (such as running a marathon) can also cause damage to blood cells in the legs.

Paroxysmal nocturnal haemoglobinuria

Otherwise known as PNH this is an acquired genetic condition, which leads to the red blood cells becoming irregular owing to a deficiency of specific types of protein. The body breaks these red blood cells down quicker than usual, and the condition can remain constant at a minor level or flare up suddenly. Individuals with PNH have a higher risk of blood clots and decreased levels of platelets and white blood cells.

Other sources of harm to red blood cells

Infections can harm red blood cells as can toxic chemicals and external agents, including snake venom, tick-borne diseases and malaria.

Other terms for haemolytic anaemia

  • Alloimmune haemolytic anaemia.
  • Autoimmune haemolytic anaemia.
  • Drug-induced haemolytic anaemia.
  • Haemoglobin anaemia caused by G6PD deficiency (deficiency of an enzyme termed G6PD).
  • Haemolytic anaemia (brought on by chemicals or exposure to toxins).
  • Hereditary elliptocytosis
  • Hereditary ovalocytosis
  • Hereditary spherocytosis
  • Idiopathic autoimmune haemolytic anaemia
  • Immune haemolytic anaemia
  • Microangiopathic haemolytic anaemia
  • Paroxysmal nocturnal haemoglobinuria
  • Pyruvate kinase deficiency
  • Sickle cell anaemia
  • Thalassaemia

What causes haemolytic anaemia?

Several classes of haemolytic anaemia exist, but the cause of all is premature red blood cell damage (haemolysis). However, the causes of premature haemolysis do vary according to the class of haemolytic anaemia.

Inherited haemolytic anaemia causes

It becomes apparent when there is difficulty with the genes which affect red blood cell construction. Individuals who have inherited types of haemolytic anaemia inherit a defective gene from a single or both parents, which causes them to produce irregular red blood cells. Different genes are responsible for various categories of inherited haemolytic anaemia, and abnormalities may affect the chemistry of the cell, the cell membrane or the manufacture of haemoglobin.

Acquired haemolytic anaemia causes

In such cases the red blood cells are in a good condition but are destroyed prematurely due to disease, infection, taking medication or an immune response. The cells can be broken down in the bloodstream or in the spleen (the spleen is the organ responsible for breaking down red blood cells and removing abnormal ones from the bloodstream).

Who is affected?

Most types occur as frequently in men as they do women and affect all ages. But autoimmune haemolytic anaemia is more common in females over the age of forty, and G6PD deficiency is predominant amongst males. Persons of all backgrounds are affected by haemolytic anaemia, but some types are more common amongst certain races. Sickle cell anaemia, for example, is much more common in African American men.

What symptoms and signs of haemolytic anaemia are there?

Signs of haemolytic anaemia vary according to the class of anaemia and condition severity. Some people do not experience symptoms at all, while others may develop severe symptoms. A majority of the indicators of haemolytic anaemia are associated with other forms of anaemia.

Symptoms of anaemia

The main sign of anaemia is extreme tiredness. This is because the tissues in the body are not receiving enough oxygen via the bloodstream. An insufficiency of oxygen can also cause the following symptoms:

  • Dizziness.
  • Weakness.
  • Headaches.
  • Struggling for breath.
  • Passing out (this is most common when moving suddenly; for instance, when standing up from a sitting position).
  • Paleness (in the skin, nail beds, gums and tongue).

In people with anaemia the heart has to work harder than usual to pump blood around the body. This may cause symptoms such as:

  • Irregular heartbeat.
  • Fast heart rate.
  • A heart murmur.

Haemolytic anaemia symptoms

  • Jaundice: this occurs when the skin and whites of the eyes appear yellow in colour. This results from haemoglobin being released into the bloodstream when red blood cells are broken down. The haemoglobin is turned into bilirubin, a yellow substance, causing jaundice. This can also cause urine to be darker than usual.
  • Abdominal soreness (in the topmost area of the abdomen): if the amount of cholesterol and bilirubin is elevated, this can cause the formation of gallstones.
  • Leg ulcers and leg pain: in severe cases of sickle cell anaemia, the blood vessels can become blocked by abnormally shaped cells. This prevents the blood from flowing freely and increases the risk of leg ulcers.
  • Severe response to a blood transfusion: haemolytic anaemia can cause the body to react abnormally to a blood transfusion. Symptoms can include chills, fever, shock and low blood pressure.

What is the diagnosis procedure for haemolytic anaemia?

The identification of haemolytic anaemia is based on a series of methods, including family and medical history, a physical examination and conducting diagnostic tests.

Which specialists are involved?

Your family doctor should be the first port of call if you experience any of the symptoms listed above. They may be able to diagnose haemolytic anaemia or can refer you to a specialist for further tests. This may include a haematologist (a specialist in blood disorders) or a cardiologist (a specialist in heart conditions). Those with a family history of inherited haemolytic anaemia might be advised to see a genetic counsellor.

Family and medical history

When you see your doctor they will ask you questions regarding your medical history; if, for example, you have any underlying medical condition, have had any previous treatment for illnesses or are taking any medication, and also what symptoms are present. You will also be asked if any of your family have anaemia or were treated for it before. You may also be asked if you know of anything that could have damaged your red blood cells.

Physical examination

Your GP will examine you to look for symptoms of anaemia and will be looking out for:

  • Pale skin, nail beds and gums.
  • Jaundice (yellowing of the skin and whites of the eyes).
  • A fast or irregular heartbeat.
  • Engorged liver or spleen.
  • Signs of internal bleeding in the rectum or pelvis.

Diagnostic tests

If the doctor suspects you have haemolytic anaemia they will advise a series of tests:

  • Complete blood count: the initial test is almost always the complete blood count (also known as the full blood count). This analyses several things, including the quantity of red blood cells, the amount of haemoglobin in the blood and the haematocrit level (the proportion of blood composed of red blood cells). A haemoglobin reading of below 11g/Dl usually indicates anaemia, while a haematocrit percentage of below 32 percent is usually an indicator of anaemia. The full blood count also examines the shape and size of red blood cells, the amount of platelets (cells involved in the blood clotting process) and the quantity of white blood cells (cells involved in combating infections).
  • Supplementary blood tests: should the full blood count show that you have anaemia, the physician can order a series of investigations to establish the source and degree of the condition.

Examples of these tests include:

  • Reticulocyte (immature red blood cells) count: analyses the speed of red blood cell manufacture in the bone marrow. Often individuals with haemolytic anaemia have a higher result than average, since the bone marrow works harder to produce more red blood cells.
  • Peripheral smear: involves the analysis of blood cells using a microscope by a pathologist. They will look for signs of unusually shaped red blood cells.
  • Coombs’ test: used to look for the existence of antibodies working in opposition to red blood cells.
  • Haptoglobin, liver function and bilirubin tests: when the red blood cells are broken down the haemoglobin is released into the bloodstream and unites with haptoglobin. If the amount of haptoglobin is low this may be an indicator of haemolytic anaemia. Bilirubin levels may be higher than normal if an individual has haemolytic anaemia. However, high levels are associated with other conditions, including liver disease, and so this test should be carried out alongside others. Liver function analysis may be carried out to resolve the cause of high bilirubin levels.
  • Haemoglobin electrophoresis: identifies abnormal haemoglobin.
  • Test for paroxysmal nocturnal haemoglobinuria (PNH): checks for missing proteins in the red blood cells.
  • Osmotic fragility analysis: checks for unusually weak red blood cells; this is identifiable in people with hereditary spherocytosis.
  • G6PD deficiency: a rapid fluorescent spot test can check for the presence of the glucose-6 phosphate dehydrogenase enzyme.

Bone marrow tests

Doctors may advise testing of the bone marrow, which involves looking at a sample of tissue using a microscope. This sample of tissue can be taken during a small biopsy procedure, or doctors may carry out an aspiration where bone marrow fluid is removed using a fine needle.

Examinations for other causes of haemolytic anaemia

Anaemia has several possible causes and so doctors may advise tests for other conditions, including:

  • Kidney failure.
  • Liver disease.
  • Iron deficiency.
  • Vitamins B12 and C and folate deficiencies.

What treatment is used for haemolytic anaemia?

Aims of treatment

The aims of treatment are to lessen haemolysis (break down of cells), boost the red blood cell count and treat the cause of anaemia.

The type of treatment will be based on the individual. Factors including the source and degree of the condition will be taken into account, and the category of haemolytic anaemia may also affect the choice of treatment. Other factors, such as age and general health, will be taken into account. Inherited haemolytic anaemia requires lifelong management, while acquired haemolytic anaemia is often addressed by treating the fundamental source.

Who requires treatment?

Treatment may not be necessary in mild cases. However, the patient’s condition will be monitored closely. Inherited haemolytic anaemia requires lifelong treatment, while severe cases of anaemia can be serious if not properly treated.

Forms of treatment

Various treatments are used for individuals with haemolytic anaemia. These include a blood transfusion, medication, changes to routine, surgery, plasmapheresis and a stem cell or bone marrow transplant.

Blood transfusion: blood transfusions are for patients with severe cases of anaemia. They are done by means of a vein and involve using somebody else’s blood. The blood needs to be checked to ensure that it is a close match (the same blood group). Patients who have regular blood transfusions will have normal tests to check that they do not have a build-up of iron.

Medication: some forms of haemolytic anaemia are able to be effectively treated with medication. This is often the case with autoimmune haemolytic anaemia, when corticosteroid medications (usually prednisone) are used to repress the actions of the immune system. If corticosteroids are not effective other drugs may be used, including cyclophosphamide, danazol and azathioprine. Intravenous gamma globulin can also be used to stem the production of antibodies working in opposition to red blood cells.

Plasmapheresis: this treatment involves taking antibodies from the red blood cells and may be recommended if other solutions have been ineffective.

Surgery: surgery is sometimes required to take out the spleen. This is an organ located in the topmost area of the abdomen, which is responsible for the removal of irregular red blood cells from the circulatory system. If the spleen is enlarged or infected it may take away a greater level of red blood cells than usual. This can result in anaemia.

Stem cell or bone marrow transplant: a transplant may be required if anaemia is brought on by problems with the bone marrow being unable to produce healthy red blood cells. Donor bone marrow is often taken from the pelvis and given through a transfusion in the vein. Stem cells can be matched using umbilical cord blood and donors are usually family members. The stem cells then develop into healthy red blood cells.

Changes to way of life: in cases where anaemia is triggered by exposure to the cold (the cold triggers the production of antibodies working in opposition to the red blood cells) staying away from cold temperature and wrapping up warm can help to prevent haemolysis. It is particularly important to keep the extremities warm (the hands, ears and feet) by wearing hats, scarves and gloves, thick socks, shoes and earmuffs. For people who inherit G6PD deficiency (glucose-6 phosphate dehydrogenase deficiency) it is possible to prevent anaemia by averting triggers, including certain types of medication.

Is there a way to prevent haemolytic anaemia?

It is impossible to prevent inherited categories of haemolytic anaemia because they are passed down from parents to children. However, in the case of G6PD deficiency, anaemia can be put off by averting triggers of haemolysis such as certain types of medication.

Adverse reactions to transfusions can be warded off by carefully matching the blood types. If a pregnant female is rhesus negative and her baby has a positive blood type, the mother will be given medication called RhoGam to prevent the mother’s body producing antibodies in opposition to the baby’s blood type.

Life with haemolytic anaemia

Mild cases may not lead to the development of any symptoms, and people can normally live a normal, healthy life with treatment. In cases of inherited haemolytic anaemia lifelong management is required, but most people are able to live an active and fulfilling life. It is important for anaemia to be managed effectively, as it can be serious if left without being treated.

Ongoing health needs

If you are diagnosed with haemolytic anaemia it is important that steps are taken to boost general health. These include adopting a healthy lifestyle, seeing your GP regularly and following clinician advice with regards to lifestyle and treatment. It is advisable to have a flu jab once a year and avoid going out in the cold without layering up and covering your extremities. Those with G6PD deficiency are advised to steer clear of particular types of medication.

Suggested physical activity

Exercise is important in the maintenance of good health. But always check with your physician if you are planning to start a new fitness regime. They will be able to advise which activities will be most beneficial, seen as some sports can make the condition worse.

Defence from infection

A physician can advise on how best to lessen the chances of developing infections, which may include cleaning your hands regularly, steering clear of ill people and staying away from crowded places.

Haemolytic anaemia in children

Most parents are eager to find out as much information about their child’s condition as possible. This is why it is advisable to spend time with your child’s care team, to ensure that you know about the condition and how best to care for your child. It is also beneficial if parents talk to their children’s friends, relatives and teachers about anaemia, so that they understand how to look after the child and are aware of the condition. Once children are older it is natural for them to take more of an interest in their condition, and it is beneficial to allow them to have greater input in treatment decisions. If you have any queries or worries you should talk to the care team, who will be able to answer questions and give relevant information and advice.

Haemolytic anaemia: the key factors

  • Haemolytic anaemia is an uncommon type of anaemia. It is apparent when the premature damage of red blood cells occur (the process is known as haemolysis, and the usual lifespan of a red blood cell is 120 days).
  • There are two major categories of haemolytic anaemia; inherited and acquired. Inherited haemolytic anaemia is passed on to children from parents, while acquired haemolytic anaemia is brought on by other factors.
  • Inherited haemolytic anaemia leads to the body producing irregular red blood cells. The abnormality may affect the surface membrane of the cell, the composition of the cell or actual manufacture of haemoglobin. The red blood cells may die or be damaged by the body ahead of time.
  • Acquired haemolytic anaemia is brought on by infection, disease, exposure to certain medication or an abnormal immune response (immune system conditions).
  • The cause is unable to be identified in certain cases.
  • Haemolytic anaemia can impact both sexes and people of different ages. However, some forms of the condition are more common in certain races.
  • Common signs include fatigue, weakness and struggling for breath. Additional symptoms may be jaundice and an engorged spleen.
  • A series of tests, including a physical examination, medical history, blood tests and supplementary diagnostic tests, are used to diagnose haemolytic anaemia. The initial test to be carried out is usually a complete (or full) blood count. Further analyses may be required to establish the class of haemolytic anaemia.
  • Treatment for haemolytic anaemia is based on the severity and type of condition, in addition to the individual’s age and general health. No treatment may be required in mild cases, while inherited forms of the condition require lifelong treatment.
  • Treatment options include stem cell or bone marrow transplant, blood transfusion, surgery, medication, plasmapheresis and changes to routine.
  • Patients may be advised to stay away from certain sporting activities, and a doctor will be able to recommend suitable exercises.
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