Last reviewed: 27 Dec 2020
Last updated: 29 Sep 2020



History and exam

Key diagnostic factors

  • presence of risk factors
  • old age
  • history of gastric surgery (gastrectomy, or bypass for obesity)

Other diagnostic factors

  • paraesthesias
  • vegan and strict vegetarian diet
  • chronic gastrointestinal disease (e.g., Crohn's disease or coeliac disease)
  • medicine (proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants)
  • ataxia
  • decreased vibration sense
  • positive Romberg's test
  • pallor
  • petechiae
  • glossitis
  • angular cheilitis
  • cognitive impairment

Risk factors

  • ¬†age >65 years
  • gastric surgery (bypass or resection)
  • chronic gastrointestinal (GI) disease
  • vegan diet
  • metformin use
  • H2 receptor antagonist or proton-pump inhibitor use
  • Helicobacter pylori infection
  • anticonvulsant use
  • diabetes mellitus
  • pregnancy

Diagnostic investigations

1st investigations to order

  • FBC
  • peripheral blood smear
  • serum vitamin B12
  • reticulocyte count
More 1st investigations to order

Investigations to consider

  • methylmalonic acid (MMA)
  • homocysteine
  • holotranscobalamin
  • intrinsic factor (IF) antibody
  • antiparietal cell (APC) antibody
  • serum gastrin (fasting)
More investigations to consider

Treatment algorithm


Robert C. Oh


Faculty Development Fellowship

Madigan Army Medical Center




RCO declares that he has no competing interests.

Peer reviewersVIEW ALL

Chief Fellow

Section of Hematology and Oncology

Department of Internal Medicine

Wake Forest University Baptist Medical Center




RC declares that she has no competing interests.

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