Anaemia of chronic disease

• What is Anaemia of Chronic Disease
• Statistics on Anaemia of Chronic Disease
• Risk Factors for Anaemia of Chronic Disease
• Progression of Anaemia of Chronic Disease
• Symptoms of Anaemia of Chronic Disease
• Clinical Examination of Anaemia of Chronic Disease
• How is Anaemia of Chronic Disease Diagnosed?
• Prognosis of Anaemia of Chronic Disease
• How is Anaemia of Chronic Disease Treated?
• Anaemia of Chronic Disease References

What is Anaemia of Chronic Disease

Anaemia is a condition where there is a low level of a substance called haemoglobin in the blood. This haemoglobin is responsible for the transport of oxygen around the blood within red blood cells. The most common cause is a low level of iron (iron deficiency anaemia), which is required to create the haemoglobin. The second most common cause is anaemia of chronic disease.

Anaemia of chronic disease is a condition where the anaemia is actually caused by a long-term inflammation that is present is many different types of diseases. When you get inflammation, the body releases lots of different chemicals (called ‘cytokines‘) into the blood stream which help the body to heal itself. If inflammation is present for a very long time however, then these cytokines can affect the production of haemoglobin and lead to anaemia.

They do this in several different ways. Firstly, several of the chemicals lower the production of a hormone (a kind of signalling chemical) called ‘erythropoietin‘. Erythropoietin signals to the body to increase the production of red blood cells and haemoglobin, and so since these inflammatory cytokines lower how much is being produced, it can lead to anaemia.

Another product of inflammation is the production of a chemical called ‘hepcidin’ which is created by the liver and stops iron from being absorbed in the intestines, and without iron haemoglobin cannot form.

Some of the cytokines can also cause the immune system to gobble up more of the iron that is in the blood, as well as destroying the red blood cells earlier and absorbing the iron within them into the immune cells. The immune cells also change their structure so that it is harder to actually get iron out of them, meaning that it is locked inside and not accessible by other parts of the body.

Statistics on Anaemia of Chronic Disease

Anaemia of chronic disease is the second most common type of anaemia, behind only iron deficiency anaemia and it may be the most common cause of anaemia for hospitalised patients.

The rates for some conditions are as follows:

• Up to 95% of patients with an acute infection (short-term) or chronic infection (ongoing for more than 6 months);
• Up to 77% of cancer patients;
• Up to 81% of people with autoimmune conditions;
• Up to 70% of patients who have rejection following an organ transplant;
• Up to 50% of patients with chronic kidney disease and inflammation.
• Up to 40% of patients with cardiovascular disease;
• Approximately 46% of patients with Human Immunodeficiency Virus (HIV) infection;
• One-third of patients with inflammatory bowel disease;
• 67% of patients with hepatitis C; and
• 12.5% of the elderly population

Risk Factors for Anaemia of Chronic Disease

There are some diseases in particular that can lead to anaemia of chronic disease, such as:

• Chronic infections such as:
  • Osteomyelitis (an infection of the bone);
  • Infective endocarditis (an infection of the heart valves); and
  • Lung abscess;
• Immune disorders such as:
  • Rheumatoid arthritis;
  • Non-infective enteritis and colitis;
  • Systemic lupus erythematosus (SLE);
  • Vasculitis;
  • Sarcoidosis;
• Cancers
• Chronic Kidney disease.

Progression of Anaemia of Chronic Disease

Anaemia of chronic disease appears gradually during the course of the underlying disease causing the condition. It can improve with effective management of the chronic disease.

Symptoms of Anaemia of Chronic Disease

People with anaemia of chronic disease can have symptoms such as:

• Fatigue;
• Headaches;
• Faintness;
• Breathlessness;
• Angina;
• Intermittent claudication (pain in the muscles of the legs leading to limping or lameness);
• Heart palpitations;
• Impaired cognitive function (decreased ability to think or concentrate); and/or
• Depression.

Clinical Examination of Anaemia of Chronic Disease

When a doctor is examining you, they will be looking for signs of anaemia and possible underlying conditions. They can look for some things such as:

• Pallor (paleness), although this may only be seen when the anaemia is severe;
• A fast heart beat;
• A sound in your heart beat called a murmur;
• Evidence of heart failure such as swelling in the legs and pleural effusions (fluid on the lungs).

How is Anaemia of Chronic Disease Diagnosed?

A blood test called a full blood count can be very useful and is required for diagnosis as it gives the levels of haemoglobin in the blood. It will also give information about the size of the red blood cells, as well as how much haemoglobin each cell contains. Usually an anaemia of chronic disease will have normally sized red blood cells (called normocytic) which have a normal amount of haemoglobin in them (called ‘normochromic’ as they are the right colour).

Another useful blood test is to do an ‘iron study’ as this will show how much iron there is in the blood as well as showing various other factors such as how much iron the blood has the potential to bind.

Prognosis of Anaemia of Chronic Disease

The outcome of this disease will greatly depend on the severity, what the underlying cause is, as well as how well you respond to treatment.

Generally when anaemia occurs with an underlying condition it is associated with:

• A less favourable outcome of the underlying condition;
• Longer hospitalisation stays;
• Poorer quality of life;
• Cognitive (brain) impairment;
• Heart failure; and
• Increased morbidity.

It may result in increased symptoms of the underlying condition and even accelerate disease progression.

In the surgical setting, it is important for both the surgeon and anaesthetist to be aware of any co-existing anaemia as it may increase the need for blood transfusions, contribute to delirium, bleeding and/or fatigue after the operation.

Where the anaemia is corrected to within certain levels (discussed further in treatment below) quality of life and energy levels can be improved.

Cancer

In cancer patients, anaemia is associated with poor survival, such that relative risk of death was increased by 65% in cancer patients with anaemia. It is also associated with greater fatigue, which can lead to reduced ability to work and perform activities of daily living and contribute to social isolation.

Chronic Kidney Disease

Patients with chronic kidney disease that have coexisting anaemia experience:

• Reduced quality of life;
• Cognitive impairment;
• Sleep disturbance;
• Disease progression;
• Increased cardiovascular morbidity and mortality;
• Reduced exercise tolerance, angina, and worsening of heart failure (where this already exists);
• Poorer organ function after renal transplantation surgery; and
• Increased mortality.

HIV/AIDs

Anaemia in patients with HIV/AIDS is associated with:

• Quicker disease progression from HIV to AIDS;
• Decreased survival, such that the risk of death is up to 70% greater;
• Increased need for transfusions;
• Increased fatigue; and
• Poorer quality of life.

Cardiovascular Disease

In heart failure patients, anaemia is associated with reduced quality of life scores, a predictor of patients requiring rehospitalisation and is associated with increased mortality. In patients following a myocardial infarction (heart attack), the presence of anaemia is a risk factor for death. Similarly, in patients following coronary artery bypass surgery, anaemia is associated with increased adverse events.

Elderly persons

In the elderly, anaemia is associated with a more rapid decline in physical function. It is associated with:

• Increased risk of falls;
• Weakness, muscle wasting and immobility;
• Cardiovascular and neurologic impairments;
• Depression and dementia;
• Hospitalisation;
• Dependency on long term care or institutionalisation; and
• Mortality.

How is Anaemia of Chronic Disease Treated?

In anaemia of chronic disease, the best and most important treatment is to keep the underlying condition under control. When the condition resolves then the anaemia should also resolve. However, in some extreme cases a blood transfusion may be needed so that the body still has enough haemoglobin to transport oxygen effectively around the body.

Agents that stimulate the body to increase the production of red blood cells, called Erythropoietin Stimulating Agents (ESAs) are also sometimes used to help treat anaemia of chronic disease. These medications are commonly used in patients with chronic kidney disease that require dialysis.

Giving iron either orally as a tablet or as an infusion into the veins may have some benefits in some patients, although it is not the best or most common form of therapy. It is especially useful in patients who have a poor response to treatment with ESAs.

New medications that target the protein hepcidin are also being created and tested. These agents aim to either decrease its production or block its action. When released by the liver, the end result of this protein is to decrease iron absorption from the intestines and prevent iron being released from body stores. Therefore if the production of this protein is decreased or it is unable to carry out its function, more iron can be absorbed from the diet and the iron stored in the body can be released to create a normal level of iron in the bloodstream available for use by the body.

Anaemia of Chronic Disease References

1. Adamson JW. Iron deficiency and other hypoproliferative anaemias. In: Braunwald E, Fauci AS, Kasper DL, et al. Harrison’s Principles of Internal Medicine (16th edition). New York: McGraw-Hill Publishing; 2005. Book
2. Cotran RS, Kumar V, Collins T, Robbins SL. Robbins Pathologic Basis of Disease (6th edition). Philadelphia: WB Saunders Company; 1999. Book
3. Kumar P, Clark M (eds). Clinical Medicine (6th edition). Edinburgh: WB Saunders Company; 2005. Book
4. Eprex [online]. St Leonards, NSW: MIMS Online; 2003 [cited 2 July 2003]. Available from: [URL link]
5. Murtagh J. Murtagh’s General Practice (4th edition). North Ryde, NSW: McGraw Hill Australia; 2007. Book
6. Weiss G, Goodnough LT. Anaemia of chronic disease. N Engl J Med. 2005;352(10):1011-23. [Abstract]

Symptoms of This Disease:

• Neutropenia
• Anaemia

Drugs/Products Used in the Treatment of This Disease:

• Aranesp (Darbepoetin alfa)
• Eprex (Epoetin alfa )
• Ferrum H (Iron polymaltose complex)
• Neo-Recormon (Epoetin beta)