Safe Use of Hydroxyurea in Sickle Cell Disease Patients Hospitalized for Painful Vaso-Occlusive Episodes: Results of the Randomized, Open-Label Helps Study

Painful vaso-occlusive episodes (VOE) constitute the most frequent acute complication of sickle cell disease (SCD). However, despite the high economic and personal burden of hospitalization for VOE, there exists no therapeutic approach for VOE other than pain management and hydration. Hydroxyurea (HU) is frequently used continuously to augment levels of fetal hemoglobin (HbF) in patients with SCD, in association with clinical amelioration. However, in addition to its cytostatic effects, HU has immediate anti-inflammatory effects that inhibit vaso-occlusive processes in the microcirculation of mice with SCD, mediated by stimulation of cyclic guanosine monophosphate (cGMP) signaling (Almeida et al., Blood 120(14):2879, 2012). The Hydroxyurea in the Emergency Room to Lessen Pain in Sickle Cell Crisis (HELPS) study (NCT03062501) was a phase II, single-center, randomized, open-label interventional Study (Phase II) designed to evaluate, primarily, the safety of moderate-to-high daily doses of HU in SCD patients in the acute phase of VOE management. Thirty HbSS patients were included in the study within 24h of VOE onset at the Hemorio, Rio de Janeiro, Brazil. Inclusion criteria were: Arrival at the ER within 8h previous to inclusion, confirmed VOE associated with a pain scale score of > 6 within the last 24h, and a pain score of >4 at the time of inclusion. Patients with baseline neutrophil counts Financial Support: FAPESP, Brazil. Disclosures Fertrin: Agios Pharmaceuticals, Inc.: Research Funding. OffLabel Disclosure: Use of up to 3 doses of hydroxyurea (30-45 mg/kg/day) in patients with sickle cell disease hospitalized for acute painful vaso-occlusive episodes.