title: Erythrocyte aging as a mechanism of anemia and a biomarker of device thrombosis in continuous-flow left ventricular assist devices.
abstract: BACKGROUND
  Blood trauma caused by continuous-flow left ventricular assist devices (CF-LVADs) has been associated with device thrombosis and anemia. Accurate in vivo quantification of erythrocyte turnover and its contribution to CF-LVAD complications have yet to be elucidated.
  
  
  METHODS
  We investigated the age (lifespan) of circulating erythrocytes in subjects with CF-LVAD. Erythrocyte lifespan is a quantitative indicator of in vivo erythrocyte turnover that can be accurately derived from measurement of the exhaled carbon monoxide (CO) level. Sixty non-smoking subjects were prospectively enrolled: 25 had a CF-LVAD without thrombosis; 10 had a CF-LVAD with thrombosis; and 25 were normal controls. End-tidal breath CO levels were measured and used to calculate erythrocyte lifespan.
  
  
  RESULTS
  The mean erythrocyte lifespan was significantly shorter in CF-LVAD subjects with (29.7 ± 14.9 days) compared to those without (65.0 ± 17.3 days) device thrombosis (p < 0.0001). The lifespans in these 2 groups were significantly shorter compared with normal controls (96.0 ± 24.9 days, both p < 0.0001). A receiver operator curve demonstrated high sensitivity-specificity for use of erythrocyte lifespan to detect device thrombosis (AUC = 0.94). In addition, all CF-LVAD subjects had low hemoglobin (11.8 ± 2.0 g/dl), and their anemia was normochromic normocytic with elevated mean reticulocyte counts. Erythrocyte lifespan correlated significantly with mean corpuscular hemoglobin concentration (r = 0.56, p = 0.0005) and red cell distribution width (r = -0.65, p < 0.001), but not with reticulocyte count (r = 0.27, p = 0.32).
  
  
  CONCLUSIONS
  Erythrocyte lifespan is substantially reduced in subjects with a CF-LVAD, which was more pronounced in the presence of device thrombosis. The etiology of anemia in CF-LVAD was primarily due to accelerated erythrocyte aging. Further studies are needed to determine whether erythrocyte lifespan could provide a practical means of detecting subtle pre-clinical thrombosis.
authors.affiliation: Texas Heart Institute, Baylor College of Medicine, Houston, Texas, USA. Electronic address: ziad.taimeh@bcm.edu.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Taimeh
authors.affiliation: Lillehei Heart Institute, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Koene
authors.affiliation: Lillehei Heart Institute, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Furne
authors.affiliation: Lillehei Heart Institute, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Singal
authors.affiliation: Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Eckman
authors.affiliation: Minneapolis Veterans Affairs Hospital, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Levitt
authors.affiliation: Lillehei Heart Institute, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Pritzker
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D004905:Erythrocyte Aging / Q000502:physiology*; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000473:pathology*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011475:Prosthesis Failure; D012189:Retrospective Studies; D013927:Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers
keywords: erythrocyte lifespan; exhaled carbon monoxide; heart failure; pump thrombosis; red blood cell survival; ventricular assist device