Effect of hydroxyurea on the rheological properties of sickle erythrocytes in vivo.
We have monitored the rheological effects of hydroxyurea (HU) on erythrocytes obtained from two patients with severe sickle cell anemia who were enrolled in a therapeutic trial of this drug. Erythrocyte membrane stability and whole cell and membrane deformability of red cells from treated and untreated patients and normal controls were determined in room air using an ektacytometer--a laser viscodiffractometer. The percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. F reticulocytes (FR), absolute F reticulocytes (AFR), and F cells (FC) were determined by single-cell radial immunolgic assays. After 1 year of treatment with HU, there was a significant increase in the level of hemoglobin (Hb) F, FR, AFR, and FC. The degree of anemia remained the same, but there was significant increase in the mean cell volume (MCV) and a significant decrease in the mean corpuscular Hb concentration (MCHC). Whole cell deformability improved by twofold, but membrane stability remained within normal limits. The hydration status of sickle erythrocytes improved as was indicated by a change toward normal in gradient osmotic ektacytometry, an increase in RBC K+ content, a decrease in percent of dense cells, and a decrease in the MCHC. The data indicate that, in addition to its effect on the production of Hb, F, HU has a salutary effect on whole cell deformability and on the hydration status of sickle erythrocytes. Determination of the rheological properties of erythrocytes may be of value in monitoring the response to HU.
Cardeza Foundation for Hematologic Research, Philadelphia, PA 19107.
S K
SK
Ballas
G J
GJ
Dover
S
S
Charache
D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004909:Erythrocyte Indices; D004910:Erythrocyte Membrane / Q000187:drug effects; D005838:Genotype; D005914:Globins / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*
D005914:Globins; D006918:Hydroxyurea