title: Erythropoietin production rate in phlebotomy-induced acute anemia.
abstract: OBJECTIVE
  To estimate the rate of erythropoietin (EPO) production under physiological, conditions and to examine the regulatory mechanism of EPO production in response to acute phlebotomy-induced anemia.
  
  
  METHODS
  Six sheep each underwent two phlebotomies in which the hemoglobin (Hb) was reduced to 3-4 g/dl over 4-5 h. The EPO plasma level, reticulocytes, Hb and EPO clearance were followed by frequent blood sampling. The EPO production rate was determined by a semi-parametric method based on a disposition decomposition analysis that accounts for the nonlinear disposition kinetics of EPO and corrects for time-dependent changes in the clearance.
  
  
  RESULTS
  The controlled drop in hemoglobin resulted in an abrupt increase in the plasma EPO concentration (peak level 812+/-40 mU/ml, mean+/-CV%) that was followed by a rapid drop 2-4 days after the phlebotomy at a time when the sheep were still anemic (Hb=4.3+/-16 g/dl). The EPO production rate at baseline was 43+/-52 U/day/kg and the amounts of EPO produced over an 8 day period resulting from the first and second phlebotomy were 2927+/-40 U/kg and 3012+/-31 U/kg, respectively.
  
  
  CONCLUSIONS
  The rapid reduction in the EPO plasma level observed 2-4 days following the phlebotomy cannot be explained solely by the increase in EPO clearance but also by a reduction in EPO production.
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: N H
authors.initials: NH
authors.lastname: Al-Huniti
authors.forename: J A
authors.initials: JA
authors.lastname: Widness
authors.forename: R L
authors.initials: RL
authors.lastname: Schmidt
authors.forename: P
authors.initials: P
authors.lastname: Veng-Pedersen
mesh_terms: D000208:Acute Disease; D000740:Anemia / Q000097:blood* / Q000209:etiology; D000818:Animals; D004921:Erythropoietin / Q000096:biosynthesis* / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism; D016014:Linear Models; D008954:Models, Biological; D017711:Nonlinear Dynamics; D018962:Phlebotomy / Q000009:adverse effects*; D012756:Sheep; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin