Managing Complications Of Sickle Cell Disease

Introduction

Sickle Cell Disease (SCD) is one of the most common genetic conditions affecting approximately 1 in 2000 births in England. Black African and Black African-Caribbean descendants are historically at higher risk of this disorder. Indeed, in the UK, approximately 8% of black people carry the gene for SCD. 

The complications associated with SCD are incredibly painful and greatly affect the quality of life of affected individuals. In this article, we will discuss some of the short- and long-term complications of SCD, and what you can do to manage them. 

What is sickle cell disease?

SCD refers to a group of genetic conditions that affect the body’s red blood cells (RBCs). RBCs play an important role in maintaining adequate circulation and are responsible for transporting oxygen and carbon dioxide both towards and away from our muscles and tissues. Healthy RBCs are disc-shaped and have flexible membranes which allow them to move easily through smaller blood vessels. 

In SCD sufferers, a genetic mutation in the gene responsible for making haemoglobin causes RBCs to be sickle-shaped, rather than disc-shaped.¹ Sickle-shaped RBCs exhibit decreased deformability and increased viscosity. This can slow the flow of blood and even construct it completely if the abnormally-shaped RBCs get stuck to the lining of small blood vessels. The obstruction of blood flow is incredibly dangerous and can cause damage to various organs.

Overview of SCD complications

Most complications of SCD are caused by Insufficient oxygen supply to the body’s tissues. There are two main types of complications: acute and chronic. Acute complications occur in the short-term, whilst chronic complications are long-term problems that can gradually worsen over time. 

Understanding sickle cell complications

Types of SCD complications

Acute complications occur as a result of the deformation (or ‘sickling’) of the RBCs. Environmental factors can affect the rate of sickling, such as:

• Extreme exercise
• Infections
• Reduced oxygen in the air (for example, at high altitude)
• Dehydration

The prevalence of chronic complications of SCD is increasing as people are living longer. Hence we are witnessing the long-term effects of SCD. These chronic complications can affect many different organ systems, ranging from the respiratory system to the renal and urinary systems. 

Acute complications

Acute complications of SCD include:

1) Painful episodes:

• Episodes of immense pain are known as sickle cell crises
• They are triggered by blockages in the blood vessels supplying a part of the body
• Although the blockage may occur anywhere, it most commonly occurs in the limbs or back

2) Acute chest syndrome: 

• Acute chest syndrome is characterised by severe lung problems which result in pneumonia-like symptoms
• Acute chest syndrome is triggered by RBCs sticking to the lining of blood vessels in the lungs
• It is a very serious complication and is the third leading cause of death among SCD patients.

3) Stroke:

• High rates of ischaemic strokes have been recorded in both adults and children with SCD, and are a major cause of death²
• Risk factors include acute and chronic anaemia, multiple organ dysfunction, and low haemoglobin concentration

4) Priapism: 

• Priapism is experienced by 35-90% of males suffering from SCD
• It is caused by obstructions in the drainage system of the blood vessels supplying the penis. These obstructions cause long and painful erections
• If you have an erection that lasts longer than an hour, you should go to the hospital
• An erection lasting longer than 3 hours is classed as a medical emergency requiring surgical intervention

Chronic complications of SCD

Here is a list of some chronic complications: 

1) Chronic sickle lung: 

• Often as a result of multiple episodes of acute chest syndrome 
• Characterised by chest pain, worsening lung problems, and fibrotic changes that can be seen on a CT scan

2) Hepatobiliary complications: 

• These complications are caused by injury to the blood vessels supplying the liver and can lead to abnormalities in normal liver function
• In severe cases, these injuries lead to progressive liver disease and end-stage liver disease

3) Eye complications:

• Sickle retinopathy refers to damage to the retina (layer of cells at the back of the eye) due to decreased blood supply
• Proliferative sickle retinopathy is the type most likely to cause loss of vision
• The changes in blood flow to the retina can result in the development of new small blood vessels in the peripheral part of the retina

Managing acute complications of sickle cell disease

Pain management 

The most common acute complication of SCD is intense pain. Opioids, such as morphine, are most commonly used to tackle acute pain.³ Morphine injections are given to patients in intervals between 4-6 hours, however over time a tolerance may be acquired. If a patient experiences tolerance to morphine, the frequency of injection would need to be increased to remain effective. 

Unfortunately, opioid dependence and addiction can be a side-effect of this type of pain management. 

A case report in 2010 evaluated the effectiveness of aquatic rehabilitation on the acute complications of SCD.⁴ The results described a significant decrease in pain and improved quality of life. 

Acute chest syndrome management 

Hypoxia, a low oxygen saturation of the blood, is one of the main effects of acute chest syndrome. Doctors will regularly monitor a patient's oxygen levels and supply additional oxygen when deemed necessary.⁵ 

Studies have shown that the presence of atypical respiratory pathogens predominates in cases of acute chest syndrome.⁵ Therefore, a combination of antibiotics are often used to target these atypical pathogens. 

Other methods of management include: 

• Hydration via an IV
• Analgesics (pain relief medications)
• Transfusion

Stroke management

An urgent blood transfusion is given to SCD patients who are suffering from a stroke.⁶ The aim of blood transfusion is to increase the oxygen carrying capacity of the blood to reverse the effects of blocked blood vessels and restore normal blood flow.⁷ 

Hydroxyurea is an approved drug for managing some of the acute complications of SCD.⁸ Hydroxyurea works by increasing foetal haemoglobin production, thus reducing the proportion of sickle haemoglobin in your blood.⁹ This helps prevent and reverse the effects of the blocked blood vessels associated with strokes, pain and acute chest syndrome.⁸

Preventing chronic complications of sickle cell disease

Hydroxyurea therapy

In addition to providing relief from some of the acute complications of SCD, studies have also demonstrated the use of long-term hydroxyurea therapy to prevent chronic sickle cell complications. 

Chronic SCD complications are primarily caused by recurrent damage to the blood vessels, resulting in the abnormal functioning of organ systems. Previous studies have recorded that regular hydroxyurea therapy increases the proportion of foetal haemoglobin in the blood, thus increasing the oxygen carrying capacity of blood and reducing the occurrence of SCD complications.¹⁰ 

One study examined the long-term benefits of hydroxyurea therapy over a period of 17.5 years, and found that mortality rates were lower in groups of SCD patients treated with long-term hydroxyurea therapy. However, hydroxyurea had no significant impact on the occurrence of stroke, infection, and organ dysfunction.¹¹

Blood transfusions

Blood transfusions can be used to manage the acute complications of SCD and aid in the prevention of chronic SCD complications. Transfusions aim to decrease the proportion of sickle-shaped haemoglobin and increase the oxygen-carrying capacity of the blood. Similar to hydroxyurea therapy, transfusions prevent or reverse the effects of blockages in the blood vessels.¹²

Long-term blood transfusions may be suggested by your healthcare professional to manage any recurrent pain, priapism and acute chest syndrome you may be experiencing. If first-line treatments haven't worked or are contraindicated, blood transfusions may be required. 

It’s important to note that regularly receiving blood transfusions can have a significant impact on your life. Indeed, the increased number of hospital visits needed to carry out blood transfusions may not be viable for some people. Also, the increased iron content of the blood would require you to undergo regular iron chelation treatment.

Bone marrow transplants

A bone marrow transplant is, currently, the only cure for SCD. However, it is not available for everyone. A high genetically matched donor is required to increase the chances of success. Most transplants are carried out in children.¹³ 

Transplants come with significant risks, including:

• Infection
• Seizures 
• Transplant rejection

Future directions

Gene therapy

Researchers are investigating gene therapy as a future direction to treat SCD. It involves introducing working genes to cells or changing the DNA within them to fix the faulty gene and restore proper protein function.¹³ 

Successful development of gene therapies will offer a potential treatment to SCD patients who cannot find a well-matched donor for a bone transplant.

FAQ’s

What is sickle cell disease?

Sickle cell disease is a genetic disorder resulting in abnormally shaped red blood cells. This reduces the oxygen carrying capacity of the blood. 

I carry the SCD trait. What are the chances that my child will have SCD?

If both you and your partner carry the gene, there is a 25% chance that your child will have SCD. If your partner doesn’t carry the gene, there is a 0% chance your child will have SCD, but they will have a 50% chance of also carrying the gene. 

What are the complications of SCD?

Pain, anaemia, acute chest syndrome, stroke and priapism are some complications of SCD. 

Is there a cure for SCD?

Currently, bone marrow transplants or stem cell transplants are the only cure for SCD. Although, they are not available for everyone. 

Summary

SCD can be a debilitating condition due to the range of complications associated with it. Pain, strokes and respiratory dysfunction are common complications. Complications can be controlled through pain medication, hydroxyurea therapy, blood transfusions or bone marrow transplantation. Speak to your health professional today to discuss these treatment options and see how you can best manage your symptoms.