Laboratory Evaluation for Vitamin B-12 Deficiency: The Case for Cascade Testing

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 mu mol/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.