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Hydroxyurea as an Alternate to Regular Blood Transfusions

Insights From:Thomas D. Coates, MD
Published: Thursday, Sep 24, 2015

 
Misunderstandings exist with regard to the risk/benefit profile of hydroxyurea, which have led to its underuse, according to Thomas D. Coates, MD. The drug has been shown to reduce the frequency of crisis and the duration of hospitalization by about 50%, and to decrease mortality by about 40%, he notes. Although regular blood transfusions reduce the likelihood of stroke in patients with sickle cell anemia, there is a great deal of interest in finding alternate solutions.

The SWiTCH study sought to determine whether regular transfusions could be ceased among children with a history of stroke who were receiving blood transfusions for at least 18 months. Participants who continued regular blood transfusions received the drug deferasirox for iron removal while the other study arm received hydroxyurea plus regular phlebotomy to remove excess iron accumulated from previous transfusions. The SWiTCH trial was stopped prior to reaching its primary endpoint, says Coates, but the study’s use of a composite endpoint made superiority difficult to prove.

The TWiTCH trial, a noninferiority study, then tested whether hydroxyurea could lower Transcranial Doppler blood velocity in children with sickle cell disease to a similar degree as blood transfusions. This study met its primary endpoint. The TWiTCH trial also signaled that hydroxyurea may be effective for primary stroke prevention, notes Coates.

Major strokes in children with sickle cell disease lead to motor impairment and brain damage that is comparable to what is seen in elderly patients who have had a stroke, states Coates. Many children with this disease have silent strokes that can lead to cognitive impairment later in life, making stroke prevention a major concern in this population.
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Misunderstandings exist with regard to the risk/benefit profile of hydroxyurea, which have led to its underuse, according to Thomas D. Coates, MD. The drug has been shown to reduce the frequency of crisis and the duration of hospitalization by about 50%, and to decrease mortality by about 40%, he notes. Although regular blood transfusions reduce the likelihood of stroke in patients with sickle cell anemia, there is a great deal of interest in finding alternate solutions.

The SWiTCH study sought to determine whether regular transfusions could be ceased among children with a history of stroke who were receiving blood transfusions for at least 18 months. Participants who continued regular blood transfusions received the drug deferasirox for iron removal while the other study arm received hydroxyurea plus regular phlebotomy to remove excess iron accumulated from previous transfusions. The SWiTCH trial was stopped prior to reaching its primary endpoint, says Coates, but the study’s use of a composite endpoint made superiority difficult to prove.

The TWiTCH trial, a noninferiority study, then tested whether hydroxyurea could lower Transcranial Doppler blood velocity in children with sickle cell disease to a similar degree as blood transfusions. This study met its primary endpoint. The TWiTCH trial also signaled that hydroxyurea may be effective for primary stroke prevention, notes Coates.

Major strokes in children with sickle cell disease lead to motor impairment and brain damage that is comparable to what is seen in elderly patients who have had a stroke, states Coates. Many children with this disease have silent strokes that can lead to cognitive impairment later in life, making stroke prevention a major concern in this population.
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