PMID- 9473246
OWN - NLM
STAT- MEDLINE
DCOM- 19980316
LR  - 20220330
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 91
IP  - 5
DP  - 1998 Mar 1
TI  - Intracellular hemoglobin S polymerization and the clinical severity of sickle 
      cell anemia.
PG  - 1777-83
AB  - Recent work has enabled us to quantitate the four variables (2,3-DPG 
      concentration, pHi, non-S hemoglobin composition, and O2 saturation) that 
      modulate the equilibrium solubility (csat) of Hb S inside sickle erythrocytes (SS 
      RBCs). Using measured values of mean corpuscular hemoglobin concentration (MCHC), 
      2,3-DPG concentration, and %Hb (F+A2), along with estimates of pHi and the 
      Deltacsat due to partial oxygenation of SS RBCs in the microcirculation, we 
      calculated the mean polymer fraction (fp) in erythrocytes from 46 SS homozygotes. 
      Values of fp derived from the conservation of mass equation ranged from 0.30 to 
      0.59. MCHC and %Hb F were major determinants of the magnitude of fp; 2,3-DPG 
      concentration and pHi also contributed, but to a lesser extent. A clinical 
      severity score (CSS) was assigned to each patient based on mean hospitalization 
      rate. There was a weak, but statistically significant, negative correlation 
      between fp and steady state hematocrit (P = .017), but none between fp and whole 
      blood hemoglobin concentration (P = .218). Although there was no correlation 
      between fp and mean number of hospitalization days per year, patients with the 
      greatest number of admissions and hospitalization days were found only among 
      those who had an fp > 0.45. All five patients who died during the follow-up 
      period (median, 7 years; range, 3 to 10 years) had fp values >/=0.48. However, 
      patients with few admissions, low hospitalization days, and long survivals 
      occurred at all fp levels. These results suggest that the clinical course of 
      homozygous SS disease cannot be predicted by mean fp calculations, which assume a 
      homogeneous distribution of the five variables that modulate intraerythrocytic 
      polymerization. A heterogeneous distribution is more likely; so the amount of 
      polymerized Hb S could vary considerably among cell populations. Factors such as 
      membrane abnormalities and endothelial cell interactions may also contribute to 
      clinical severity.
FAU - Poillon, W N
AU  - Poillon WN
AD  - Center for Sickle Cell Disease and Department of Pediatrics and Child Health, 
      Howard University College of Medicine, Washington, DC.
FAU - Kim, B C
AU  - Kim BC
FAU - Castro, O
AU  - Castro O
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Hemoglobin, Sickle)
RN  - 0 (Polymers)
RN  - 138-81-8 (2,3-Diphosphoglycerate)
RN  - 9034-53-1 (Hemoglobin A2)
RN  - 9034-63-3 (Fetal Hemoglobin)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - 2,3-Diphosphoglycerate/blood
MH  - Adolescent
MH  - Adult
MH  - Anemia, Sickle Cell/*blood
MH  - Erythrocyte Indices
MH  - Erythrocytes/chemistry
MH  - Female
MH  - Fetal Hemoglobin/analysis
MH  - Hemoglobin A2/analysis
MH  - Hemoglobin, Sickle/*chemistry
MH  - Hemolysis
MH  - Hospitalization
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Male
MH  - Middle Aged
MH  - Oxygen/blood
MH  - Polymers/*chemistry
EDAT- 1998/03/21 00:00
MHDA- 1998/03/21 00:01
CRDT- 1998/03/21 00:00
PHST- 1998/03/21 00:00 [pubmed]
PHST- 1998/03/21 00:01 [medline]
PHST- 1998/03/21 00:00 [entrez]
AID - S0006-4971(20)57157-7 [pii]
PST - ppublish
SO  - Blood. 1998 Mar 1;91(5):1777-83.