A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy

K. R. Bridges, G. D. Barabino, C. Brugnara, M. R. Cho, G. W. Christoph, George J Dover, B. M. Ewenstein, D. E. Golan, C. R G Guttmann, J. Hofrichter, R. V. Mulkern, B. Zhang, W. A. Eaton

Research output: Contribution to journalArticle

Abstract

During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F- cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement.

Original languageEnglish (US)
Pages (from-to)4701-4710
Number of pages10
JournalBlood
Volume88
Issue number12
StatePublished - Dec 15 1996
Externally publishedYes

Fingerprint

Hydroxyurea
Erythrocytes
Sickle Cell Anemia
Hemoglobins
Hemoglobin SC Disease
Polymerization
Microcirculation
Erythrocyte Indices
Reticulocytes
Endothelial cells
Human Umbilical Vein Endothelial Cells
Time delay
Blood
Therapeutics
Glycophorin
Fetal Hemoglobin
Cell membranes
Laminar flow
Multicenter Studies
Endothelium

ASJC Scopus subject areas

  • Hematology

Cite this

Bridges, K. R., Barabino, G. D., Brugnara, C., Cho, M. R., Christoph, G. W., Dover, G. J., ... Eaton, W. A. (1996). A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. Blood, 88(12), 4701-4710.

A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. / Bridges, K. R.; Barabino, G. D.; Brugnara, C.; Cho, M. R.; Christoph, G. W.; Dover, George J; Ewenstein, B. M.; Golan, D. E.; Guttmann, C. R G; Hofrichter, J.; Mulkern, R. V.; Zhang, B.; Eaton, W. A.

In: Blood, Vol. 88, No. 12, 15.12.1996, p. 4701-4710.

Research output: Contribution to journalArticle

Bridges, KR, Barabino, GD, Brugnara, C, Cho, MR, Christoph, GW, Dover, GJ, Ewenstein, BM, Golan, DE, Guttmann, CRG, Hofrichter, J, Mulkern, RV, Zhang, B & Eaton, WA 1996, 'A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy', Blood, vol. 88, no. 12, pp. 4701-4710.
Bridges KR, Barabino GD, Brugnara C, Cho MR, Christoph GW, Dover GJ et al. A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. Blood. 1996 Dec 15;88(12):4701-4710.
Bridges, K. R. ; Barabino, G. D. ; Brugnara, C. ; Cho, M. R. ; Christoph, G. W. ; Dover, George J ; Ewenstein, B. M. ; Golan, D. E. ; Guttmann, C. R G ; Hofrichter, J. ; Mulkern, R. V. ; Zhang, B. ; Eaton, W. A. / A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. In: Blood. 1996 ; Vol. 88, No. 12. pp. 4701-4710.
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