Anaemia of Chronic Disease

Anaemia of chronic disease occurs when long-lasting illnesses that cause inflammation affect your body’s ability to make enough healthy red blood cells, even when iron is stored in your tissues.

anemia of chronic disease, anemia of inflammation, anemia of chronic inflammation, anemia of inflammation and chronic disease, ACD, AOCD

Table of contents

• What is Anaemia of Chronic Disease?
• Who is Affected?
• What Causes This Condition?
• Signs and Symptoms
• How is it Diagnosed?
• Treatment Options
• Can it be Prevented?

What is Anaemia of Chronic Disease?

Anaemia of chronic disease happens when you have a long-term illness that lasts longer than three months and causes inflammation in your body. Chronic inflammation is when your body’s defense system stays active for a long time, responding to an ongoing health problem^[1]. This ongoing inflammation can affect your body’s ability to use iron needed to make enough red blood cells, which are the cells in your blood that carry oxygen from your lungs to all parts of your body^[1].

When you have anaemia, your blood has fewer red blood cells than normal, or your red blood cells contain less haemoglobin than they should. Haemoglobin is the iron-rich protein that allows red blood cells to carry oxygen^[3]. Without enough oxygen reaching your tissues and organs, your body cannot work properly.

In anaemia of chronic disease, your body may have a normal or even increased amount of iron stored in your tissues, but a low level of iron in your blood. The inflammation prevents your body from using stored iron to make enough healthy red blood cells^[3]. This is different from iron deficiency anaemia, where your body simply doesn’t have enough iron stored anywhere.

This condition is the second most common type of anaemia worldwide, after iron-deficiency anaemia^[1][6]. Most people who have anaemia of chronic disease have a mild form of the condition^[1].

Who is Affected?

Anyone who has a chronic illness may develop anaemia of chronic disease. However, most of the people who have this condition are age 65 and older. Studies indicate about 1 million people in the United States age 65 and older have anaemia of chronic disease^[1]. The incidence of this condition is known to increase with age, affecting 77% of elderly people in whom no clear cause of anaemia has been reported^[6].

The condition is particularly common in hospitalized or critically ill patients, where it represents the most common form of anaemia^[7]. Worldwide, low- and lower-middle income countries bear the greatest burden of anaemia, particularly affecting populations living in rural settings, in poorer households, and those who have received no formal education^[20].

What Causes This Condition?

Any chronic disease that causes inflammation is likely to cause anaemia of chronic disease^[1]. The condition affects people whose current illness triggers an active immune or inflammatory response in their body^[6].

Diseases that may cause anaemia of chronic disease include^[1]:

• Cancer and blood cancers such as lymphoma and Hodgkin disease
• Chronic kidney disease
• Heart failure (congestive heart failure)
• Autoimmune diseases, which are diseases where your immune system attacks your body instead of protecting it
• Long-term infections, such as bacterial endocarditis, osteomyelitis (bone infection), HIV/AIDS, lung abscess, hepatitis B, or hepatitis C
• Having obesity

Specific autoimmune diseases that may cause this condition include^[1]:

• Rheumatoid arthritis, which causes chronic inflammation of joints
• Systemic lupus erythematosus (or lupus), which causes tissue damage from an immune system attack on your body
• Vasculitis, an inflammation of blood vessels
• Sarcoidosis, an inflammatory disease that commonly affects the lung and lymph glands
• Inflammatory bowel disease (Crohn’s disease and ulcerative colitis), which affects the intestines

Your chronic disease affects your red blood cells in several ways. Your bone marrow, the spongy tissue inside your bones, is constantly making new red blood cells to replace dying or damaged ones. Most red blood cells live for about 120 days^[1]. A chronic disease may make red blood cells die sooner than usual or slow down red blood cell production.

Three main processes explain how chronic disease causes anaemia^[5]:

First, red blood cells may have a slightly shortened lifespan. This is thought to happen because special cells called macrophages destroy red blood cells more quickly than normal^[5].

Second, the production of new red blood cells is impaired. Your body produces less erythropoietin, a hormone made by the kidneys that signals your bone marrow to make red blood cells. Even when erythropoietin is present, your bone marrow doesn’t respond to it as well as it should. Inflammatory substances called cytokines can also directly harm the cells that develop into red blood cells^[5].

Third, and most importantly, your body’s iron metabolism changes. Your body normally recycles the iron from old red blood cells to make new ones. In anaemia of chronic disease, macrophages trap the recycled iron inside themselves. A substance called hepcidin increases during inflammation and blocks both iron absorption from food and the release of stored iron from cells^[5][6]. This means your body has less iron available to help create new red blood cells, even though iron is stored in your tissues.

Signs and Symptoms

Not everyone who has anaemia of chronic disease will notice symptoms. Some people may have no symptoms at all, while others may only notice symptoms when they’re exercising^[1][4].

When symptoms do occur, they may include^[1][2]:

• Feeling very tired or weak, sometimes too weak to manage day-to-day activities
• Feeling short of breath, especially during physical activity
• Noticing that your skin is more pale than usual
• Feeling sweaty for no reason
• Feeling dizzy or faint
• Having headaches
• Difficulty focusing and thinking clearly
• Feeling your heart pounding

The symptoms of anaemia of chronic disease are similar to those of iron-deficiency anaemia^[1]. The symptoms you experience are usually those of your underlying chronic condition combined with the effects of having anaemia^[5].

How is it Diagnosed?

Your healthcare provider will diagnose anaemia of chronic disease through blood tests and by considering your medical history. A blood test, sometimes done as part of a routine exam, tells your doctor if you have anaemia^[4].

Your doctor may diagnose you with anaemia of chronic disease if^[4]:

• You have a chronic disease or health problem that’s known to cause anaemia
• Your symptoms and test results don’t point to other types of anaemia, such as pernicious anaemia, haemolytic anaemia, or iron deficiency anaemia

Tests that may be done to diagnose anaemia or rule out other causes include^[2]:

• Complete blood count (CBC), which measures the number of red blood cells and the amount of haemoglobin
• Reticulocyte count, which measures how many young red blood cells your bone marrow is making
• Serum iron level, which measures the amount of iron in your blood
• Serum ferritin level, which indicates how much iron is stored in your body
• Transferrin or total iron binding capacity, which shows how well your blood can transport iron
• C-reactive protein and erythrocyte sedimentation rate, which measure inflammation in your body
• In rare cases, bone marrow aspiration to check for other problems

In anaemia of chronic disease, the red blood cells are usually normal-sized at first, though they may become smaller over time^[5]. Your serum iron and transferrin levels are typically low, while your serum ferritin value can be normal or elevated^[5].

It is important to rule out iron deficiency and other causes of anaemia, as misdiagnosis will in most cases lead to treatment that doesn’t work^[6]. A serum ferritin level below 100 ng/mL in a patient with inflammation suggests that iron deficiency may be present alongside anaemia of chronic disease^[5].

Treatment Options

Anaemia of chronic disease is most often treated by treating the underlying health problem that caused it^[4]. Healthcare providers treat anaemia of chronic disease by treating the underlying condition. For example, treating rheumatoid arthritis can lower inflammation, which can then improve the anaemia^[1][4].

The anemia will improve when the disease that is causing it is treated^[2]. However, this is often not feasible, especially when the underlying condition cannot be fully cured^[7].

Additional treatment options include^[2][4][6]:

Erythropoietin-stimulating agents (ESAs) may be used for anaemia caused by cancer or chronic kidney disease. These medicines help the body make more red blood cells. They are given as an injection^[4].

Blood transfusions may be necessary for severe anaemia, regardless of the cause. This involves receiving red blood cells from a donor^[4].

Iron supplementation may be used in some cases, particularly when iron deficiency is also present alongside anaemia of chronic disease^[6]. However, you should only take iron if your doctor tells you to. Unless you also have iron deficiency anaemia, taking iron does not help with anaemia of chronic disease. If your iron level is normal, taking extra iron can be dangerous^[4].

Treatment is aimed at both addressing the underlying disease and alleviating the anaemia to improve patient quality of life^[7].

Can it be Prevented?

The best way to prevent anaemia of chronic disease is to manage and treat chronic conditions that may cause it^[3]. Since anaemia of chronic disease occurs as part of a chronic inflammatory disorder, preventing or controlling the underlying condition is key.

Regular follow-up care with your healthcare provider is important if you have a chronic condition. Be sure to attend all appointments and report any new symptoms, including signs of anaemia such as unusual tiredness or weakness^[17].

If you have a chronic disease, your doctor may monitor your blood counts regularly to detect anaemia early, before symptoms become severe. Early detection allows for prompt treatment and can help prevent complications^[2].