Rapid withdrawal of voxelotor can precipitate sickle cell disease related crisis

快速停用沃克洛托可能诱发镰状细胞病相关危机

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Abstract

Sickle cell disease (SCD) is an inherited disorder characterized by abnormal mutation leading to formation of sickle red blood cells. The initial step is the formation of polymers and precipitation of Hemoglobin within the cell. voxelotor is a novel anti-polymerization drug approved for treatment of patients with SCD, resulting in improved hemoglobin level. Recently its clinical development was suspended, as concerns were raised regarding its safety and efficacy. We have evaluated 11 patients who were stable, on voxelotor for a mean period of 191 weeks (range, 8-369). We observed that upon its withdrawal, 8 patients (73%) showed a rapid onset of vaso-occlusive crisis, within a median of 4.7 days, precipitating hemolysis, with a significant drop of Hb, raised reticulocytes, bilirubin, and lactic dehydrogenase. Also, one patient (9.1%) developed acute chest syndrome, whereas five (45.5%) patients needed blood transfusions. Our data confirms that rapid withdrawal of voxelotor could precipitate severe SCD-related crisis.

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