Starting hydroxycarbamide for sickle cell disease

Introduction

Until recently, the treatment for sickle cell disease (SCD) has been limited to:

• pain relief and fluids for painful crisis
• antibiotics for infection
• blood transfusions for serious complications

Hydroxycarbamide (also known as Hydroxyurea) has been in use for several decades and can lessen the complications of sickle cell disease.

What is Hydroxycarbamide?

Hydroxycarbamide is a medicine which has been used in lots of patients with sickle cell disease.

It can reduce the frequency of daily pain at home. It can also reduce hospital admissions and life threatening complications such as chest crisis and stroke. Hydroxycarbamide can improve the quality of a someone’s life by increasing their tolerance for exercise, giving them more energy for daily activities.

It may also have a role in preventing long term lung and kidney damage and increase long term survival.

How does Hydroxycarbamide help?

Hydroxycarbamide can reduce some of the complications of sickle cell disease.

Hydroxycarbamide is now used in adults and children with moderate to severe repeated pain and chest crisis. It is also used in some children who have an increased risk of stroke after initial transfusion treatment.

The best evidence for preventing painful crisis and chest crisis comes from a large study involving several centres in America. A large group of identical patients were given either Hydroxycarbamide or a fake medicine (placebo).

Those that took the real medicine:

• had fewer painful crisis and the crisis they did have were less severe
• had fewer and less severe chest crisis (lung sickling)
• needed less blood transfusions
• needed fewer admissions to hospital
• on long term follow up are in better physical health

Over the period of follow up, patients were also less likely to die when taking Hydroxycarbamide than if they were not.

Some children having regular transfusions because of increased risk of stroke, can safely switch from transfusions to Hydroxycarbamide. This is only safe in some children who have responded well to the transfusions. Your doctor will explain this further if this is the case for your child.

How does it work?

Hydroxycarbamide is a ‘cytostatic’ medicine which stops body cells increasing in number. This has a number of beneficial effects on sickle cells.

Haemoglobin

Hydroxycarbamide increases the amount of haemoglobin (HbF) that a baby makes.

HbF is the haemoglobin which all babies make at birth. This haemoglobin is normally ‘switched off’ by 6 months of age. It is a useful haemoglobin which protects affected babies from complications of sickling.

Some people with sickle cell disease who have naturally higher levels of HbF in childhood and adult life generally have a milder disease course.

If someone’s HbF can be switched back ‘on’ by the Hydroxycarbamide, this can protect them from sickling.

The increase in HbF when taking Hydroxycarbamide takes weeks or months to reach its full potential.

Water content

Hydroxycarbamide increases the water content of the red blood cell which makes it more difficult for the red blood cell to develop a sickle shape. This then makes crisis less likely.

Sticking to the lining of the blood vessel

Hydroxycarbamide makes the red blood cell less ‘sticky’ so they do not stick to the lining of the blood vessel. This is good because sticky cells could start a crisis.

Hydroxycarbamide produces this anti-sticking effect in the first few weeks of treatment and this is one of the reasons why some people feel better soon after starting treatment.

White blood cells

Hydroxycarbamide reduces the white blood cell count, which is often raised in people with sickle cell disease. This is important because the white cells produce chemicals which can cause inflammation and might trigger sickling. Having fewer white blood cells makes this less likely.

Nitric oxide

Hydroxycarbamide also increases the levels of nitric oxide in the blood which helps with blood flow through the tissues of the body.

How can Hydroxycarbamide help in sickle cell disease?

Hydroxycarbamide is not a cure for sickle cell disease. However, it can prevent many of the complications including the following:

• number and severity of painful crisis
• number of hospital admissions
• number of acute chest syndrome events
• need for blood transfusions

It is also associated with an increase in life expectancy and quality of life.

Hydroxycarbamide does not reduce the frequency of, or prevent sickle cell complications in:

• leg ulcers
• bone damage (avascular necrosis)
• infections

What are the side effects?

All medications have side effects. The risks associated with hydroxycarbamide are low, but there are some side effects to watch out for:

• tiredness from the fall of haemoglobin
• increased risk of infection from fewer white blood cells
• bleeding from drop the platelet count

This means that your child will need regular blood counts to reduce these risks.

Contact Ward 6 urgently to arrange a blood test if your child:

• has a fever (temperature more than 37 degrees Celsius)
• feels unwell
• has any bleeding

Sometimes Hydroxycarbamide needs to be paused for a few days to let the blood count to recover.

Other side effects:

• darkened skin and nails, and sometimes skin rashes. These are usually mild
• sickness, diarrhoea, or constipation
• temporary hair loss, or thinning and dryness
• it may reduce sperm production but evidence for this is unclear. There is no evidence that either sickle cell or Hydroxycarbamide affect fertility. Teenage boys will be given the opportunity to discuss sperm conservation before starting therapy.
• there could be a risk that Hydroxycarbamide may harm an unborn baby. Women and men should stop Hydroxycarbamide when planning a pregnancy, after consultation with their doctor

How soon will it work?

Your child will need to take Hydroxycarbamide for at least 6 months before you can be sure of its full benefits.

The dose of Hydroxycarbamide may be increased every few months to have maximal effect. Your doctor will discuss your individual plan with you.

Will I need any extra tests?

Your child will have a blood test at the start of treatment, after 2 weeks of starting, or after any dose change and thereafter every 8 to 12 weeks.

How is hydroxycarbamide taken?

Hydroxycarbamide comes in several capsule sizes.

Swallow the capsules whole if possible as this will minimise contamination of the environment and those who are handling them. Drink with a full glass of water or fruit flavoured drink. Do not use milk.

Hydroxycarbamide can also be given as a liquid which must be stored in the fridge after opening and discarded after 12 weeks..

It is important that your child takes their dose every day. If they miss a dose or are sick, give them the normal dose the next day but do not double the dose.

Hydroxycarbamide will not work if it is only given occasionally and so it is important it is given daily for maximal effect.