Failure of Phenothiazines in Sickle Cell Anemia

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