Summary
Definition
History and exam
Key diagnostic factors
- old age
- history of gastric surgery (gastrectomy, or bypass for obesity)
Other diagnostic factors
- paresthesias
- vegan and strict vegetarian diet
- chronic gastrointestinal disease (e.g., Crohn disease or celiac disease)
- drug (proton-pump inhibitors [PPIs], H2 receptor antagonists, metformin, anticonvulsants)
- ataxia
- decreased vibration sense
- positive Romberg test
- pallor
- petechiae
- glossitis
- angular cheilitis
- cognitive impairment
Risk factors
- age >65 years
- gastric surgery (bypass or resection)
- chronic gastrointestinal (GI) disease
- vegan or strict vegetarian diet
- metformin use
- H2 receptor antagonist or proton-pump inhibitor (PPI) use
- Helicobacter pylori infection
- anticonvulsant use
- nitrous oxide misuse
- diabetes mellitus
- pregnancy
Diagnostic tests
1st tests to order
- CBC
- peripheral blood smear
- serum vitamin B12
- reticulocyte count
Tests to consider
- methylmalonic acid (MMA)
- homocysteine
- holotranscobalamin (hTC)
- anti-intrinsic factor antibody (anti-IFAB)
- antiparietal cell (APC) antibody
- serum gastrin (fasting)
Treatment algorithm
symptomatic
asymptomatic or borderline deficiency
Contributors
Authors
Robert C. Oh, MD, MPH, CAQSM

Chief Wellbeing Officer
VA Palo Alto Health Care System
Palo Alto
CA
Declarações
RCO declares that he has no competing interests.
Revisores
Thein Hlaing Oo, MD, FRCP Edin, FACP
Professor of Internal Medicine
Consultant Hematologist
The University of Texas MD Anderson Cancer Center
Houston
TX
Declarações
THO declares that he has no competing interests.
Rebecca Connor, MD
Chief Fellow
Section of Hematology and Oncology
Department of Internal Medicine
Wake Forest University Baptist Medical Center
Winston-Salem
NC
Declarações
RC declares that she has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
Referências
Principais artigos
Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014 Aug;166(4):496-513.Texto completo Resumo
Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med. 1999 Jun 28;159(12):1289-98.Texto completo Resumo
Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013 Jan 10;368(2):149-60. Resumo
National Institutes of Health, Office of Dietary Supplements. Vitamin B12: fact sheet for health professionals. Mar 2024 [internet publication].Texto completo
Guidelines and Protocols Advisory Committee, British Columbia. Cobalamin (vitamin B12) and folate deficiency. Apr 2024 [internet publication].Texto completo
Artigos de referência
Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.
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