Inflammatory Bowel Disease and Anaemia

Overview

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation of the gastrointestinal tract (GI).¹ These conditions include ulcerative colitis (UC), which mainly causes inflammation of the colon (part of the large intestine), and Crohn’s disease (CD), which involves deeper inflammation that can affect any part between the mouth and the anus. Living with IBD can be very hard for many patients, with symptoms like stomach pain, diarrhoea, and rectal bleeding, as well as other unpredictable symptoms affecting the eyes, skin, and liver. Moreover, IBD can also cause other health complications, making it even more difficult and affecting their quality of life.¹  Anaemia is one of the most common complications associated with IBD, to the point that it often gets overlooked and remains untreated.^2,3 Yet, it is actually a serious condition that causes fatigue and weakness, affecting people’s well-being. Anaemia can be more concerning in those with IBD, as it makes them feel sicker, leading to more hospital visits, blood transfusions, and a higher risk of death. Recognizing anaemia is important, as it is often one of the first IBD symptoms. Early detection can help people seek medical help sooner, potentially leading to earlier diagnosis and treatment, preventing further complications.⁴ Understanding how to address anaemia is important for improving the quality of life for those with IBD. This article will discuss the connection between anaemia and IBD, as well as approaches for diagnosing and treating the conditions.

What is anaemia?

About a quarter of the world's population is estimated to have anaemia, especially in individuals assigned female at birth (AFAB) and children under 5 years old.5 Anaemia occurs due to a shortage of red blood cells(cells that provide oxygen to various parts of the body) or haemoglobin, which is the protein found in red blood cells that carries oxygen. For AFAB individuals is diagnosed when haemoglobin levels fall below 12.0 g/dL, and below 13.0 g/dL for individuals assigned male at birth (AMAB). Haemoglobin is vital for transporting oxygen throughout the body. When there's a lack of red blood cells or haemoglobin, or if they're abnormal, oxygen delivery to the body's tissues decreases. This can lead to symptoms such as weakness, dizziness, shortness of breath, headaches, and cold hands or feet.⁶

There are different types of anaemia, each with its own causes and impacts. Some of the most common types include:⁶

• Iron-deficiency anaemia: Iron deficiency anaemia is the most common type of anaemia. It happens when your body lacks sufficient iron. This deficiency is usually caused by blood loss, although it can sometimes be due to poor iron absorption
• Vitamin B12-deficiency anaemia: Vitamin deficiency anaemia can happen when there are low levels of vitamin B12 or folate, mainly due to poor diet. Pernicious anaemia, for example, is a specific type of anaemia where vitamin B12 cannot be absorbed in the gastrointestinal tract
• Hemolytic anaemia: Hemolytic anaemia happens when red blood cells are destroyed faster than they can be replenished. This condition can develop rapidly or gradually, ranging from mild to severe. It often occurs due to factors such as autoimmune reactions, infections, or inherited blood conditions
• Anaemia of inflammation: Anaemia of inflammation, also known as anaemia of chronic disease (ACD), is a type of anaemia found in individuals with conditions that lead to inflammation, like infections, autoimmune disorders, cancer, and chronic kidney disease (CKD)
• Sickle cell anaemia: Sickle cell anaemia is a genetic form of hemolytic anaemia where the haemoglobin protein is abnormal. This makes red blood cells rigid, causing them to block blood flow in small blood vessels
• Aplastic anaemia: Aplastic anaemia is a rare disorder where the bone marrow fails to produce enough red and white blood cells and platelets. This results from the destruction or deficiency of blood-forming stem cells, often due to the immune system attacking these cells

What is the link between anaemia and IBD?

Anaemia can affect up to 74% of people with IBD, and is more common in Crohn's disease compared to ulcerative colitis.² Anaemia in IBD patients is often caused by multiple factors, including:⁷

Iron deficiency: Inflammation causes the body to produce hepcidin, which can block iron from entering the bloodstream and trap it in certain cells. This iron retention prevents its use for making red blood cells. Additionally, chronic bleeding from the intestines, a common issue in IBD, further depletes iron levels. 

Anaemia of chronic disorders (ACD): ACD occurs when the body cannot use iron properly, even if iron levels are normal or high. Inflammation-related proteins called cytokines reduce the lifespan of red blood cells and disrupt the production of erythropoietin, a hormone that signals the body to make new red blood cells. This results in iron being trapped in the body but unavailable for use, leading to a functional iron deficiency.

Vitamin deficiency: Deficiencies in vitamin B12 and folic acid, absorbed in the ileum and duodenum (parts of the small intestine), can lead to anaemia with larger red blood cells. This is more common in severe cases of Crohn's disease or after extensive small intestine surgery.

Drug toxicity: Medications used to treat IBD, such as sulfasalazine and azathioprine, can cause anaemia by damaging bone marrow (producing blood cells) or causing hemolysis (breakdown of red blood cells). Regular monitoring is necessary to manage these side effects.

Haemolytic anaemia: In rare cases, IBD can cause the body to destroy its own red blood cells, leading to haemolytic anaemia. This is more common in ulcerative colitis and may require immunosuppressive treatment or surgery.

How is anaemia in IBD diagnosed?

The European Crohn’s and Colitis Organization (ECCO) recommends regular anaemia screening for IBD patients based on their disease activity:⁸ 

• Patients in remission or with mild disease: Screenings should be done every six to twelve months 
• Outpatients with active disease: Screenings should be done at least every three months
• Patients at risk for vitamin B12 or folic acid deficiency (e.g., those with small bowel disease or resection): The serum levels of vitamin B12 and folic acid should be measured at least once a year

Healthcare providers diagnose anaemia using tests such as a complete blood count (CBC), serum ferritin, and transferrin saturation (TfS). However, these tests may be less accurate in patients with active IBD because inflammation can affect the results. For example, inflammation can cause ferritin levels to increase, making it difficult to accurately diagnose iron deficiency. Additionally, medications like thiopurines and sulfasalazine can also contribute to anaemia and should be considered during diagnosis.⁹

Treatment and management of anaemia in patients with IBD

To treat anaemia in patients with IBD, healthcare providers usually investigate and address the root causes before determining a treatment plan. The specific treatment will depend on the type and cause of the anaemia. Here are some treatment plans based on different types of anaemia:⁹

Iron deficiency anaemia (IDA)

IBD-related inflammation can impair iron absorption, making iron supplementation necessary. The goal is to normalize haemoglobin levels and replenish iron stores. The type of supplementation depends on the severity of the condition:

• For patients with mild disease and anaemia, oral iron supplements like ferrous fumarate, ferrous sulphate, and ferrous gluconate can be effective. However, some patients cannot tolerate these supplements. In such cases, ferric maltol offers better tolerability and effectivenes
• Patients with severe anaemia or who do not respond to oral iron supplementation might need intravenous iron supplementation. Modern preparations like ferric carboxymaltose are well-tolerated and effective, with fewer side effects than older dextran-based products
• If anaemia recurs or serum ferritin drops below 100 µg/L patients should continue with supplementation

Anaemia of chronic disease (ACD)

Treating ACD involves controlling IBD activity and addressing underlying infections, inflammation, or malignancies. Erythropoietin-stimulating agents can be used to boost red blood cell production and are often combined with intravenous iron. Anti-TNF therapy helps counteract bone marrow issues caused by TNF-α, a protein that promotes inflammation. Future treatments, such as hepcidin antagonists, have shown promising results in preclinical studies and need further evaluation in human trials.

Vitamin deficiency anaemia

Patients with active IBD or those who have undergone ileal resection may need direct supplementation of vitamin B12 and folic acid, especially if mixed anaemia or high mean corpuscular volume (MCV) levels are detected.

Summary

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease that affects the gastrointestinal tract. Along with its various complications, such as stomach pain and other unpredictable symptoms, IBD frequently leads to anaemia, a condition marked by low red blood cell or haemoglobin levels. Untreated or undiagnosed anaemia in people with IBD can worsen their condition, make them sicker, and may even increase the risk of death. Diagnosing anaemia in IBD patients requires careful consideration due to the potential impact of inflammation on test accuracy. Treatment approaches vary depending on the severity and type of anaemia, with options ranging from oral supplements to intravenous therapies. It's crucial for healthcare providers to not only address anaemia but also to manage IBD effectively, aiming for both the correction of haemoglobin levels and the control of active inflammation. Routine screening and appropriate management of anaemia should be integral parts of care for all IBD patients, offering the potential for improved quality of life and overall outcomes.