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Failure of Phenothiazines in Sickle Cell Anemia

Howard A. Pearson, MD; Ward D. Noyes, MD
JAMA. 1967;199(1):33-34. doi:10.1001/jama.1967.03120010077017.
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A beneficial effect of phenothiazine therapy on clinical symptomatology and red cell survival in patients with sickle cell anemia (hemoglobin SS) has been described by Lewis and Hathorn from Ghana.1-3 The rationale for this treatment was based on their observations of an apparently higher than expected incidence of red cell (RBC) glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients with hemoglobin SS disease when compared to normal individuals. They suggested that the enzyme deficiency might have a beneficial effect on the course of hemoglobin SS disease, thus leading to a preferential survival of those individuals with the combination. Because genetically determined G6PD deficiency was postulated to be advantageous, they then undertook treatment with pharmacologic agents which were known to inhibit the enzyme. The phenothiazine promazine (Sparine) hydrochloride inhibits G6PD4 and, in high levels, interferes with in vitro sickling.1

When promazine hydrochloride, in a


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