Membrane expansion as a mechanism explaining the antisickling action of ticlopidine observed in vitro

Ticlopidine, a platelet antiaggregant, has shown some efficacity in a clinical trial in patients with sickle cell disease. We have studied this agent in vitro to evaluate its effects on sickle erythrocyte. Ticlopidine effects sickling in vitro not by direct interaction with hemoglobin, but via strong binding to the red cell membrane. The density of the whole cell population is decreased when cells are treated with 0.1 mM ticlopidine, which is higher than the concentrations of 1 microM potentially achievable in vivo. Since hemoglobin concentration influences the delay time for gelling, its decrease in the red cell could have a beneficial effect. Such a partial inhibition of the polymerization is shown by oxygen equilibrium studies at various ionic strengths.