Introduction

Imagine being a six year old kid; you love playing with your friends, you want to be running after them, playing football, or enjoying your favourite sport. But in the midst of joyous playing, you start experiencing intense pain. It is not the first time – you have felt it before in your chest, hands, feet, and belly. These are not random pains, this is Sickle Cell Disease (SCD).

SCD affects millions all over the world. In 2021, more than 500,000 babies were born with SCD.¹

In this article, we want to help you understand why those symptoms occur and why someone with SCD experiences all those symptoms.

Overview of sickle cell disease and its symptoms

What is sickle cell disease?

SCD is a blood disorder caused by a mutation (alteration) in the genes producing haemoglobin. Haemoglobin is a protein found in our red blood cells, which are vital for transporting oxygen throughout our body. Haemoglobin is formed by four proteinic parts known as globin chains (2 alpha chains and 2 beta chains) and four haem groups, one attached to each globin chain. These haem groups each contain an iron ion, which is responsible for the oxygen-carrying property of haemoglobin.²

Why symptoms occur

A red blood cell with normal haemoglobin tends to be relatively elastic, biconcave – resembling a doughnut shape- and has the ability to pass through blood vessels easily. However, haemoglobin in SCD makes the red blood cells rigid and sticky. Instead of the usual round shape, they take on a crescent shape, which increases the likelihood of getting stuck in smaller blood vessels.³

When a person with SCD engages in aerobic activity, a significant amount of haemoglobin becomes deoxygenated. The deoxygenated haemoglobin tends to polymerise, forming rigid haemoglobin strands and distorting the shape of red blood cells. As a result, these cells become less functional and fragile.

While normal red blood cells have a lifespan of 100 +/- 20 days, sickled red blood cells only live for 10 to 20 days. The shortened lifespan, combined with blood vessel blockage, leads to oxygen deprivation in tissues, generating symptoms of SCD.³

Importance of symptom awareness

Being aware of SCD symptoms is extremely important, especially if you or someone around you is affected. Recognising and understanding the symptoms early enables early medical intervention to provide better management and avoid complications. 

Common symptoms of sickle cell disease

Pain episodes (Sickle cell crises)

A sickle cell crisis (pain crisis) is when people living with SCD experience an episode of pain, which can be recurrent.

The pain experienced in an SCD crisis is commonly described as:

• Sharp: Abrupt and cutting sensations
• Throbbing: Pulsating and rhythmic pain
• Localized: Typically affects bones and joints, although it can occur in other areas of the body as well

It is important to keep in mind that red blood cells in SCD patients do not remain in a sickle shape all the time. Certain conditions generate variation in the blood oxygenation levels, altering the shape of red blood cells.

Some factors that can trigger an SCD crisis are dehydration, infections, physical effort, and extreme temperatures. The frequency of these episodes varies from one individual to another – some may experience frequent crises while others only have a few throughout their life.

Anaemia

Based on the World Health Organization definition, anaemia is when the amount of red blood cells or concentration of haemoglobin decreases below the reference values, depending on conditions such as gender, age, pregnancy, and altitude. (4)

In the United Kingdom, the laboratories use these values:

When oxygen levels drop, our body struggles to produce energy effectively, leading to various symptoms:

1. Fatigue and weakness
   • When a significant amount of red blood cells are destroyed, the body experiences oxygen deprivation, leading to fatigue, weakness, and low energy
2. Paleness
   • Haemoglobin also acts as a pigment, giving blood its distinctive red color. Decreased haemoglobin levels make the blood appear less red, resulting in paleness, which is more apparent in the gum, lower eyelids, nails, or other areas which are normally red or pink⁶
3. Increased heart rate
   • The heart starts beating faster to compensate for oxygen deficiency
4. Additional symptoms
   • Other symptoms can occur: headaches, becoming intolerant to cold, dizziness, appetite disturbances, and loss of weight⁶

Impact on daily life

These symptoms can affect the daily life of the individual, making it difficult to concentrate due to constantly being cold and tired.^5,6

Swelling in hands and feet (Dactylitis)

There are parts of our body where the blood vessels have a smaller diameter; some examples include the hands and feet. When sickled red blood cells form a blockage at the small blood vessels in the fingers, it reduces oxygen delivery, leading to an inflammatory reaction, resulting in swelling and pain in hands and feet.⁷

This occurs more frequently in infants and young children as they have more tiny blood vessels than adults.

Frequent infections

People with SCD are more prone to infections for various reasons: 

• Spleen dysfunction: The spleen has an important function in filtering bacteria. Blocked blood flow and infarctions damage the spleen, which reduces its ability to function properly over time
• Constant inflammatory reactions: The continuous cycle of blood vessel blockage and red blood cell destruction keeps the immune system consistently in an activated state. Over time, the immune system becomes less reactive to new infections
• Bone marrow stress: the bone marrow is under constant stress by the constant production of red blood cells to make up for the sickled red blood cells. As a result, the production of white blood cells (leukocytes) is reduced⁸

A common infection in SCD is pneumonia, which exhibits symptoms like fever, cough, and pain.⁹

Other infections include:⁸

.

Severe and chronic symptoms

Acute chest syndrome

Acute chest syndrome (ACS) refers to a painful episode that occurs when the blockage occurs in the blood vessels of the sternum (the bone in the chest). Symptoms include chest pain, coughing, difficulty breathing, and fever. ACS can rapidly worsen, thus, it is necessary to seek medical attention immediately.^10,11

Stroke

SCD increases the stroke risk as constant blockages occur. Someone with a stroke will manifest sudden weakness, speech difficulties, vision problems, and palsy, generally in one side of the body.^3,10

Organ damage

Since every single organ receives blood innervation, blockage can lead to oxygen deprivation and tissue damage. Commonly affected organs include the spleen, liver and kidneys.¹²

Vision problems

The lack of blood in the eyes due to blockage of small vessels can cause abnormal growth of blood vessels and may even lead to bleeding or retinal detachment. The iris can become weak due to oxygen deprivation, which is characterised by blurry vision, floaters or sudden vision loss. As such, individuals with SCD should have regular eye examinations.¹²

Managing and monitoring symptoms

Pain management

The medications commonly used are non-steroidal anti-inflammatory drugs (NSAIDs) for relieving pain, such as ibuprofen. Heat therapy, relaxation techniques, and hydration are common non-pharmacological methods. They can be used to alleviate mild symptoms, but professional care is required if the individual experiences severe pain or any of the symptoms described previously.

Preventing and managing infections

To reduce the risk of infections, it is important to stay up-to-date on vaccinations recommended by healthcare providers. In some cases, preventive antibiotics may be prescribed to prevent punctual infections.

To recognise an infection, it is necessary to pay attention to symptoms like fever, pain, fatigue, cough, difficulty breathing, and changes in the skin such as redness, warmth, swelling, or drainage from wounds or surgical sites.¹⁴

Neurological symptoms such as confusion, irritability, and headache could suggest meningitis or other important infections. You should seek medical attention if you experience fever, severe pain, difficulty breathing, and unexplained symptoms.

Regular monitoring for severe symptoms

A person living with SCD should have health checkups periodically to prevent further complications. Professionals of different specialities, haematologists, cardiologists, infectious disease specialists, neurologists, and others will help to address severe symptoms.¹¹

Summary

Recognising the symptoms of SCD is crucial for early intervention and effective management. Understanding the signs, from painful crises to anaemia and infections, enables better support for those affected and helps them live normal lives. Awareness and education are key in empowering patients, families, and communities to take steps to manage this challenging but manageable condition.