title: Laboratory evaluation for vitamin B12 deficiency: the case for cascade testing.
abstract: OBJECTIVE
  Potential vitamin B(12) deficiency is a common clinical diagnostic problem, and many providers have a low threshold for initiating therapy. The goal of this study was to systematically evaluate current practice patterns regarding the laboratory evaluation of suspected vitamin B(12) deficiency.
  
  
  METHODS
  This retrospective study reviewed the electronic medical records of 192 patients initiated on intramuscular vitamin B(12) injections.
  
  
  RESULTS
  Only 12 patients had objectively documented hematologic responses: decrease of mean corpuscular volume by ≥5 fL with stable or improved hemoglobin. Another 5 patients had equivocal hematologic responses. There was one plausible neurologic response. Thus, only 18 (9.4%) of 192 patients had data supportive of a clinical response. In these 18 patients, the baseline serum B(12) level was ≤107 pg/mL; only 3 patients also had a baseline serum methylmalonic acid level, which was ≥1.29 μmol/L in all 3 patients.
  
  
  CONCLUSIONS
  Currently, only a small minority of patients initiated on intramuscular vitamin B(12) supplementation derive any meaningful clinical benefit. Furthermore, current testing recommendations for vitamin B(12) deficiency are usually not followed. Up-front ordering of a diagnostic testing cascade is recommended to improve compliance; an example is presented with decision points chosen to improve specificity for clinically evident vitamin B(12) deficiency without loss of sensitivity. Ultimately, a better understanding of vitamin B(12) physiology is needed to develop and evaluate laboratory tests that more accurately reflect true intracellular vitamin B(12) status.
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Berg
authors.forename: Gene R
authors.initials: GR
authors.lastname: Shaw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D012189:Retrospective Studies; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D008764:Methylmalonic Acid; D014805:Vitamin B 12