Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with
sickle cell disease (SCD). However, all completed clinical trials of
hydroxyurea have excluded patients with
hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular
dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on
hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of
hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with
hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to
hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on
hydroxyurea. Of the four placed on dual
hydroxyurea and phlebotomy
therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual
therapy with
hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with
hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing
hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of
hydroxyurea and
hydroxyurea with phlebotomy in patients with HbSC disease.