title: Hemorrhage-adjusted iron requirements, hematinics and hepcidin define hereditary hemorrhagic telangiectasia as a model of hemorrhagic iron deficiency.
abstract: BACKGROUND
  Iron deficiency anemia remains a major global health problem. Higher iron demands provide the potential for a targeted preventative approach before anemia develops. The primary study objective was to develop and validate a metric that stratifies recommended dietary iron intake to compensate for patient-specific non-menstrual hemorrhagic losses. The secondary objective was to examine whether iron deficiency can be attributed to under-replacement of epistaxis (nosebleed) hemorrhagic iron losses in hereditary hemorrhagic telangiectasia (HHT).
  
  
  RESULTS
  The hemorrhage adjusted iron requirement (HAIR) sums the recommended dietary allowance, and iron required to replace additional quantified hemorrhagic losses, based on the pre-menopausal increment to compensate for menstrual losses (formula provided). In a study population of 50 HHT patients completing concurrent dietary and nosebleed questionnaires, 43/50 (86%) met their recommended dietary allowance, but only 10/50 (20%) met their HAIR. Higher HAIR was a powerful predictor of lower hemoglobin (p = 0.009), lower mean corpuscular hemoglobin content (p<0.001), lower log-transformed serum iron (p = 0.009), and higher log-transformed red cell distribution width (p<0.001). There was no evidence of generalised abnormalities in iron handling Ferritin and ferritin(2) explained 60% of the hepcidin variance (p<0.001), and the mean hepcidinferritin ratio was similar to reported controls. Iron supplement use increased the proportion of individuals meeting their HAIR, and blunted associations between HAIR and hematinic indices. Once adjusted for supplement use however, reciprocal relationships between HAIR and hemoglobin/serum iron persisted. Of 568 individuals using iron tablets, most reported problems completing the course. For patients with hereditary hemorrhagic telangiectasia, persistent anemia was reported three-times more frequently if iron tablets caused diarrhea or needed to be stopped.
  
  
  CONCLUSIONS
  HAIR values, providing an indication of individuals' iron requirements, may be a useful tool in prevention, assessment and management of iron deficiency. Iron deficiency in HHT can be explained by under-replacement of nosebleed hemorrhagic iron losses.
authors.affiliation: National Heart and Lung Institute, Cardiovascular Sciences, Imperial College London, London, United Kingdom ; Diabetes and Nutritional Sciences Division, King's College London, School of Medicine, London, United Kingdom ; University of Liverpool Medical School, Liverpool, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Finnamore
authors.forename: James
authors.initials: J
authors.lastname: Le Couteur
authors.forename: Mary
authors.initials: M
authors.lastname: Hickson
authors.forename: Mark
authors.initials: M
authors.lastname: Busbridge
authors.forename: Kevin
authors.initials: K
authors.lastname: Whelan
authors.forename: Claire L
authors.initials: CL
authors.lastname: Shovlin
mesh_terms: D000328:Adult; D000368:Aged; D004032:Diet; D019587:Dietary Supplements; D004844:Epistaxis / Q000453:epidemiology; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D064451:Hepcidins / Q000378:metabolism*; D006801:Humans; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D064167:Recommended Dietary Allowances; D012044:Regression Analysis; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000378:metabolism*; D055815:Young Adult
chemical_list: D006397:Hematinics; D064451:Hepcidins; D019266:Iron, Dietary