title: Differences in blood volume components between hyporesponders and responders to erythropoietin alfa: the heart failure with preserved ejection fraction (HFPEF) anemia trial.
abstract: BACKGROUND
  Hyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy.
  
  
  METHODS
  As part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with (131)iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg, <1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls.
  
  
  RESULTS
  Nine of 28 subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but less of a red cell deficit (-96.2 ± 126 vs -402.5 ± 80.6 mL; P = .04) and a greater plasma volume expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r = 0.91; P < .0001) as well as a decline in plasma volume (r = -0.55; P = .06).
  
  
  CONCLUSIONS
  Among older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.
authors.affiliation: Columbia University Medical Center, New York, New York.
authors.forename: Margarita
authors.initials: M
authors.lastname: Borovka
authors.forename: Sergio
authors.initials: S
authors.lastname: Teruya
authors.forename: Julissa
authors.initials: J
authors.lastname: Alvarez
authors.forename: Stephen
authors.initials: S
authors.lastname: Helmke
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology*; D000068817:Epoetin Alfa; D004911:Erythrocyte Volume / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010953:Plasma Volume / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa
keywords: Anemia; blood volume; erythropoietin alfa; heart failure