PMID- 1712641
OWN - NLM
STAT- MEDLINE
DCOM- 19910819
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 78
IP  - 1
DP  - 1991 Jul 1
TI  - Effects of hydroxyurea on hemoglobin F and water content in the red blood cells 
      of dogs and of patients with sickle cell anemia.
PG  - 212-6
AB  - A rationale for clinical trials of hydroxyurea (HU) treatment in sickle cell 
      disease is that the agent increases red blood cell (RBC) fetal hemoglobin 
      content. However, an additional effect of HU is to raise the mean corpuscular 
      volume (MCV). To investigate the action of HU in a species that makes no 
      electrophoretically distinguishable fetal hemoglobin, we treated dogs with the 
      drug and compared their response to that of five patients with sickle cell 
      anemia. Both dogs and patients had an increase in MCV, but the effect of HU 
      treatment on the mean corpuscular hemoglobin concentration (MCHC), density, and 
      water content of the RBCs differed in the two species. The dog RBCs became low in 
      MCHC, high in ion and water content, and low in mean density. Thus, HU can raise 
      MCV and lower MCHC without influencing fetal hemoglobin synthesis. A different 
      pattern was seen in the sickle cell patients during HU treatment. Although the 
      MCV of their RBCs increased, there was no change in MCHC, ion content, or mean 
      density. A notable change in the sickle cell patients' blood was that two 
      subpopulations of cells were nearly eliminated during HU treatment; the hypodense 
      reticulocyte fraction and the hyperdense fraction that contains irreversibly 
      sickled cells. These findings lead us to suggest that trials of HU in sickle cell 
      disease must recognize the possibility that any beneficial effect of this agent 
      might be due not only to an increase in hemoglobin F alone, but perhaps also to 
      the associated increase in MCV or the altered RBC density profile.
FAU - Orringer, E P
AU  - Orringer EP
AD  - Department of Medicine, University of North Carolina at Chapel Hill 27599-7600.
FAU - Blythe, D S
AU  - Blythe DS
FAU - Johnson, A E
AU  - Johnson AE
FAU - Phillips, G Jr
AU  - Phillips G Jr
FAU - Dover, G J
AU  - Dover GJ
FAU - Parker, J C
AU  - Parker JC
LA  - eng
GR  - DK-11356/DK/NIDDK NIH HHS/United States
GR  - HL-28391/HL/NHLBI NIH HHS/United States
GR  - HL-40169/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 059QF0KO0R (Water)
RN  - 9034-63-3 (Fetal Hemoglobin)
RN  - X6Q56QN5QC (Hydroxyurea)
SB  - IM
MH  - Administration, Oral
MH  - Anemia, Sickle Cell/*blood/drug therapy
MH  - Animals
MH  - Dogs
MH  - Erythrocyte Count/drug effects
MH  - Erythrocytes/chemistry/*drug effects/metabolism
MH  - Fetal Hemoglobin/*analysis/metabolism
MH  - Humans
MH  - Hydroxyurea/administration & dosage/*pharmacology/therapeutic use
MH  - Osmolar Concentration
MH  - Water/*analysis/metabolism
EDAT- 1991/07/11 19:15
MHDA- 2001/03/28 10:01
CRDT- 1991/07/11 19:15
PHST- 1991/07/11 19:15 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1991/07/11 19:15 [entrez]
AID - S0006-4971(20)82998-X [pii]
PST - ppublish
SO  - Blood. 1991 Jul 1;78(1):212-6.