In vitro exposure to hydroxyurea reduces sickle red blood cell deformability.
Hydroxyurea is a drug that is used to treat some patients with sickle cell disease. We have measured the deformability of sickle erythrocytes incubated in hydroxyurea in vitro and found that hydroxyurea acts to decrease the deformability of these cells. The deformability of normal erythrocytes was not significantly affected by hydroxyurea except at very high concentrations. Hydroxyurea also did not consistently reduce the deformability of sickle erythrocyte ghosts. We propose that the decreased deformability, observed in vitro, is due to the formation of methemoglobin and other oxidative processes resulting from the reaction of hydroxyurea and oxyhemoglobin. Although the reaction with normal hemoglobin is similar to that of sickle hemoglobin, the sickle erythrocytes are affected more. We propose that the sickle erythrocyte membrane is more susceptible to the reaction products of the reaction of hemoglobin and hydroxyurea. An earlier report has shown that hydroxyurea increases the deformability of erythrocytes in patients on hydroxyurea. Taken together, these data suggest that the improved rheological properties of sickle erythrocytes in vivo are due to the elevated numbers of F cells [cells with fetal hemoglobin]. The presence of the nitrosyl hemoglobin or methemoglobin from the reaction with hydroxyurea may also benefit patients in vivo by reducing sickling.
Huang
Z
Z
Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109-7507, USA.
Louderback
J G
JG
King
S B
SB
Ballas
S K
SK
Kim-Shapiro
D B
DB
D000755:Anemia, Sickle Cell / Q000097:blood*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects; D004913:Erythrocytes, Abnormal / Q000187:drug effects*; D005319:Fetal Hemoglobin / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008706:Methemoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000187:drug effects
D006454:Hemoglobins; D010108:Oxyhemoglobins; C008657:nitrosyl hemoglobin; D008706:Methemoglobin; D005319:Fetal Hemoglobin; D006918:Hydroxyurea