title: Persistent increase in red cell size distribution width after acute diseases: A biomarker of hypoxemia?
abstract: BACKGROUND
  A biomarker of hypoxic exposure would be useful in clinical diagnosis and prognosis. Acute hypoxia stimulates large increases in serum erythropoietin (EPO), and EPO induces formation of characteristic enlarged red blood cells (RBCs). The presence of large RBCs perturbs red cell distribution width (RDW).
  
  
  METHODS
  Using a >2M patient medical claims database, the human pathome was scanned for diseases where RDW rose 0-50days following a new diagnosis. The course of RDW after selected diagnoses was visualized by registering RDW measurements by diagnosis date.
  
  
  RESULTS
  Acute hemorrhage, which provokes EPO-driven erythropoiesis, is followed by increases in RDW but not mean cell volume (MCV). Similar RDW increases follow many acute diseases with risk of hypoxia, including heart failure, pneumonia, atelectasis, pulmonary embolism, pneumothorax, and sepsis. Elevations reach maximum within 1month after onset and subside to pre-disease levels about 6months later. Unlike the case with iron-deficiency anemia (IDA), RDW elevations after hypoxia-associated diseases are unaccompanied by discernible change in average RBC size.
  
  
  CONCLUSIONS
  As predicted by a model risk pathway linking hypoxia to formation of enlarged RBCs via EPO, acute hypoxemia-related disease episodes induce change in RBC size distribution. Further study is needed to explore whether a more sensitive and specific signal can be extracted from the fine structure of the RBC size distribution routinely measured in automated hemocytometers.
authors.affiliation: Global Medicines Development, AstraZeneca LLC, Wilmington, DE, USA. Electronic address: ycasjw@gmail.com.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Yčas
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horrow
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D048429:Cell Size; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000473:pathology*; D004921:Erythropoietin / Q000097:blood; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D004921:Erythropoietin
keywords: Biomarker; Erythropoiesis; Hypoxia; Nucleated red blood cell; Pathome; Red cell distribution width