Angela Rankine-Mullings | One medication, multiple benefits

Sickle cell disease (SCD) results from the inheritance of a sickle cell gene from both parents or a sickle gene from one parent and another abnormal haemoglobin gene from the other parent. This causes abnormalities in haemoglobin, which is a protein in red blood cells.

Red blood cells in persons living with SCD will change from a round biconcave shape to a sickle or crescent shape under certain conditions. These sickled cells are fragile, that is, they break easily and have difficulty moving around the body through the blood circulation. Red blood cells use their haemoglobin to carry oxygen to our organs. However, sickled red cells cannot carry enough oxygen because of their abnormal haemoglobin. These effects of SCD and other factors are the basis of sickle cell complications, of which painful crisis is the most frequent, but there are many others.

Hydroxyurea (HU), also called hydroxycarbamide, is the cornerstone of SCD treatment. It is the only available highly effective medication that is used to treat persons living with SCD. It reduces sickling of red cells and other effects of SCD. Hydroxyurea is available as tablets or suspension.

An understanding of how the medication works and the benefits of treatment is important for persons living with SCD and their families to allow better adherence to medication guidelines and optimise treatment. Here are some frequently asked questions.

HOW DOES HYDROXYUREA WORK?

Foetal haemoglobin (HbF) is a type of haemoglobin which carries oxygen but is unaffected by SCD. It is produced naturally by the body in utero and as babies, it protects persons from the effects of SCD. Hence, babies up to six months usually remain well, before HbF levels fall. Hydroxyurea turns on the production of HbF in the body when it is taken, so HbF is produced again. Hydroxyurea improves the blood count. The red cells in the blood of persons taking hydroxyurea are more likely to keep their shape, that is a round and biconcave shape, rather than become sickle shaped. They are also stronger and do not break as easily as before treatment and can move around the circulation easily. This allows the red cells to function better and improves its ability to carry oxygen to important organs and to the entire body.

Hydroxyurea is preventative treatment. The goal of preventative treatment is to decrease the effects of SCD by reducing the chance of complications occurring.

WHEN IS HYDROXYUREA MOST RECOMMENDED?

Hydroxyurea is offered to persons with severe or frequent painful crisis to decrease the number of painful crises experienced. Persons with severe acute chest crisis, severe anaemia or very low blood also benefit from hydroxyurea.

Some manifestations of SCD that require treatment may not cause noticeable problems. For example, children with SCD can be at increased risk of stroke and remain well. It is important that children are screened for stroke with a test known as Transcranial Doppler (TCD). Hydroxyurea is given to persons with a history of stroke to prevent a repeat stroke or to prevent stroke in children who have high TCD results.

In high-income countries, all infants with severe forms of SCD are offered hydroxyurea at nine months of age, even if they have not yet had symptoms.

HOW IS HYDROXYUREA TAKEN?

Hydroxyurea is taken once daily by mouth, as directed by your doctor.

Taking medication regularly is required for maximum benefit.

Important tips:

• Take as prescribed

• Report a pregnancy

• Keep clinic appointments

• Do not share medication

• Store medicine in a safe place

• Take at a regular time of the day

Hydroxyurea modifies the course and lessens the effects of SCD. From experiences of persons living with SCD who are taking hydroxyurea there have been reports of less painful crisis, less admissions to hospital, less days missed from school or work, less acute chest syndrome and better health compared to before hydroxyurea treatment. Research also indicates that these benefits have been reported in large groups of persons who take hydroxyurea all over the world.

Benefits only occur IF hydroxyurea is taken correctly, that is, once daily or as directed. Optimal hydroxyurea treatment for maximum benefit is a partnership between patient/families and physicians.

WHAT ARE THE SIDE EFFECTS?

Hydroxyurea treatment is safe. Hydroxyurea is considered standard of care. Persons are counselled on the side effects by the doctor and given the opportunities to ask questions before treatment. Benefits must be considered against possible side effects. Leading research shows that early concerns about processes that can cause cancer that could be associated with hydroxyurea have not been realised. Observations for long-term effects of hydroxyurea are ongoing, including its effect on fertility. Hydroxyurea treatment may lower blood cells too much. This is expected so doctors monitor persons with blood tests. Occasional to rare side effects include stomach upset and hair loss. Skin and nail changes have been observed.

Hydroxyurea treatment has benefited persons with SCD. It is an important game-changer in sickle cell treatment and an exciting development that all persons living with SCD or their caregivers should know about.

Dr Angela Rankine-Mullings is a senior lecturer at Sickle Cell Unit, Caribbean Institute for Health Research, The University of the West Indies. Send feedback to angela.rankinemullings@uwimona.edu.jm