Resumo do NICE

As recomendações neste tópico do Best Practice são baseadas em diretrizes internacionais autorizadas, complementadas por evidências e opiniões de especialistas relevantes para a prática recentes. Para seu maior benefício resumimos abaixo as principais recomendações das diretrizes do NICE relevantes.

Principais recomendações do NICE sobre diagnóstico

This summary covers vitamin B12 deficiency in people aged 16 and over.

Common symptoms and signs of vitamin B12 deficiency include:

  • Abnormal findings on a blood count (e.g., anaemia or macrocytosis)

  • Cognitive difficulties (e.g., difficulty concentrating or short-term memory loss)

  • Eyesight problems related to optic nerve dysfunction (e.g., blurred vision, optic atrophy, visual field loss [scotoma])

  • Glossitis

  • Neurological or mobility problems related to peripheral neuropathy, or to central nervous system disease including myelopathy (e.g., balance issues and falls caused by impaired proprioception and linked to sensory ataxia; impaired gait; paraesthesia)

  • Symptoms or signs of anaemia that suggest iron treatment is not working properly during pregnancy or breastfeeding

  • Unexplained fatigue.

Be aware that symptoms and signs of vitamin B12 deficiency can vary person to person and are often not exclusive to the condition. Also be aware that the condition can be associated with mental health problems (e.g., symptoms of depression, anxiety or psychosis).

Common risk factors for vitamin B12 deficiency include:

  • Diet low in vitamin B12 (without regular use of over-the-counter preparations)

  • Family history of vitamin B12 deficiency or an autoimmune condition

  • Health conditions (e.g., atrophic gastritis affecting the gastric body; coeliac disease or other autoimmune condition [e.g., thyroid disease, Sjögren's syndrome, type 1 diabetes])

  • Medicines (e.g., colchicine, H₂-receptor antagonists, metformin, phenobarbital, pregabalin, primidone, proton-pump inhibitors, topiramate)

  • Previous abdominal or pelvic radiotherapy

  • Previous gastrointestinal surgery (e.g., many bariatric surgeries [e.g., Roux-en-Y gastric bypass or sleeve gastrectomy], gastrectomy, terminal ileal resection)

    • Note that vitamin B12 deficiency is highly likely after total gastrectomy or complete terminal ileal resection, if not receiving vitamin B12 replacement

  • Recreational nitrous oxide use.

Offer an initial diagnostic test for vitamin B12 deficiency to people who have at least 1 common symptom or sign and at least 1 common risk factor for the condition (see above).

  • Use clinical judgement when deciding whether to test people who have at least 1 common symptom or sign but no common risk factors.

  • Do not rule out a diagnosis of vitamin B12 deficiency based solely on the absence of either anaemia or macrocytosis.

Use either total B12 (serum cobalamin) or active B12 (serum holotranscobalamin) as the initial test for suspected vitamin B12 deficiency unless:

  • The test needs to be done during pregnancy (then use active B12 as initial test),or

  • Recreational nitrous oxide use is the suspected cause of deficiency

    • Use plasma homocysteine or serum methylmalonic acid (MMA) as the initial test. If using plasma homocysteine, refer to secondary care phlebotomy services for this test.

Take blood samples for diagnostic tests before starting vitamin B12 replacement.

  • When offering an initial diagnostic test, ask the person if they are already using an over-the-counter preparation containing vitamin B12 (e.g., vitamin B12 tablets, injections or transdermal patches), and what type and dosage they are using.

Do not delay vitamin B12 replacement while awaiting test results of people with suspected megaloblastic anaemia and neurological symptoms, especially symptoms related to sub-acute combined degeneration of the spinal cord.

  • Consider starting vitamin B12 replacement while awaiting test results of people with suspected vitamin B12 deficiency that is a side effect of taking medicine.

See the NICE guideline for information on how to interpret initial test results (including factors that can affect results [e.g., ethnicity]).

Consider a further test to measure serum MMA concentrations in people with symptoms or signs of vitamin B12 deficiency and an indeterminate total or active B12 test result.

Consider vitamin B12 replacement for people with an indeterminate initial test result who:

  • Have a condition or symptom that may deteriorate rapidly and have a major effect on quality of life (e.g., neurological or haematological conditions such as ataxia or anaemia),or

  • Have a condition or suspected condition that is an irreversible cause of vitamin B12 deficiency (e.g., autoimmune gastritis),or

  • Have had surgery that can cause vitamin B12 deficiency,or

  • Are pregnant or breastfeeding.

    If also performing a further test to measure serum MMA concentrations, start vitamin B12 replacement while awaiting the result.

Advise people with an indeterminate total or active B12 result but no symptoms or signs of vitamin B12 deficiency to seek medical help if they develop symptoms or signs of deficiency.

If the initial test result suggests vitamin B12 deficiency is unlikely, investigate other causes of symptoms and if there are still symptoms 3 to 6 months later, consider repeating the test.

Further investigations to identify the cause of vitamin B12 deficiency (e.g., an anti-intrinsic factor antibody test if autoimmune gastritis is suspected, serological testing for coeliac disease) should be considered in selected people. See the NICE guideline for more information on investigating the cause of vitamin B12 deficiency.

If vitamin B12 deficiency is diagnosed during pregnancy or breastfeeding and autoimmune gastritis is the suspected cause, start intramuscular vitamin B12 replacement without awaiting further test results.

Link para a orientação do NICE

Vitamin B12 deficiency in over 16s: diagnosis and management (NG239) March 2024. https://www.nice.org.uk/guidance/ng239

Principais recomendações do NICE sobre tratamento

Continue with vitamin B12 replacement if treatment was started before pregnancy or breastfeeding and review this treatment at a later date.

If malabsorption is the confirmed or suspected cause of vitamin B12 deficiency:

  • Offer lifelong intramuscular vitamin B12 replacement if:

    • Autoimmune gastritis is the cause (or suspected cause)or

    • The person has had a total gastrectomy, or complete terminal ileal resection

  • Offer vitamin B12 replacement (and consider intramuscular instead of oral replacement) if malabsorption is not caused by autoimmune gastritis, total gastrectomy, or complete terminal ileal resection (e.g., malabsorption caused by coeliac disease, partial gastrectomy or some forms of bariatric surgery).

If vitamin B12 deficiency is medicine-induced:

  • Offer either intramuscular or oral vitamin B12 replacement (based on clinical judgement and the person's preference) while they are taking the medicine,and

  • If appropriate, review whether the medicine causing the side effect is still needed or can be changed. Review the need for vitamin B12 replacement if the medicine is stopped or changed and there are no longer symptoms of vitamin B12 deficiency.

If vitamin B12 deficiency is caused by recreational nitrous oxide use:

  • Offer either intramuscular or oral vitamin B12 replacement (based on clinical judgement and the person's preference)

  • Advise the person to stop using nitrous oxide recreationally

    • Review the need for vitamin B12 replacement if recreational use of nitrous oxide stops and there are no longer symptoms of vitamin B12 deficiency.

If diet is the suspected cause of vitamin B12 deficiency:

  • Ask what they eat or drink (including any foods/drinks that contain vitamin B12) and if they take (or plan to take) any over-the-counter preparations containing vitamin B12

    • Advise people who take (or plan to take) over-the-counter oral supplements that contain vitamin B12 that some do not contain enough (or the right type of) vitamin B12 to be effective, and to choose one that contains at least 1 of the following: cyanocobalamin, methylcobalamin, or adenosylcobalamin

  • Check whether they have any symptoms, signs or risk factors that could suggest another cause of vitamin B12 deficiency. Be aware that diet (e.g., vegetarian, vegan) may not be the cause, or the only cause, of a person’s vitamin B12 deficiency

    • Consider further investigations to explore other causes if the person suggests or gives information that raises suspicion that deficiency is not linked to diet

  • If the person has suspected or confirmed vitamin B12 deficiency because their diet lacks vitamin B12, tell them where to find information on improving their intake (e.g., food sources) and consider oral vitamin B12 replacement. Consider intramuscular instead of oral replacement if:

    • The person has another condition that may deteriorate rapidly and have a major effect on quality of life (e.g., a neurological or haematological condition)

    • There are concerns about adherence to oral treatment.

If the cause of vitamin B12 deficiency is uncertain, and malabsorption is not suspected based on the results of further testing or investigations, offer vitamin B12 replacement.

  • Consider oral instead of intramuscular replacement and review response to treatment at the first follow-up appointment.

Advise people starting vitamin B12 replacement when to seek medical help if symptoms have not improved, worsen or return, or new symptoms appear, after starting treatment.

Ongoing care and follow up

Offer an initial follow-up appointment to people who are having vitamin B12 replacement:

  • At 3 months after treatment initiation, or earlier depending on symptom severity,or

  • At 1 month after treatment initiation if they are pregnant or breastfeeding.

At each follow-up appointment, ask if symptoms have improved or worsened, or if there are new symptoms that could be linked to vitamin B12 deficiency.

At follow-up appointments for people taking oral vitamin B12 replacement:

  • Check they are taking the correct dosage (and address any adherence concerns)

  • If there are new or worsening symptoms, consider an alternative diagnosis and, if the person did not have serum MMA or plasma homocysteine as an initial diagnostic test, consider further testing with serum MMA (or plasma homocysteine if this is unavailable) and continue existing treatment while awaiting the result

    • If the person has further testing and the result suggests B12 deficiency (or is uncertain), or if the person had serum MMA or plasma homocysteine as an initial diagnostic test, consider their treatment preferences and either increase the oral dosage to the maximum licensed dosage or (if already taking the maximum licensed oral dosage) switch to intramuscular vitamin B12 injections

    • If the person has further testing and the result suggests there is no longer B12 deficiency but there are still symptoms, explore alternative diagnoses

  • If symptoms have not sufficiently improved (so they are still interfering with normal daily activities), consider the person’s treatment preferences and either increase the oral dosage to the maximum licensed dosage or (if already taking the maximum licensed oral dosage) switch to intramuscular vitamin B12 injections

  • If symptoms have resolved or improved (so that they are no longer affecting normal daily activities):

    • Continue oral replacement and agree a date for reassessment if the cause (or suspected cause) of deficiency has not been addressed, or is unknown

    • Consider stopping treatment if the cause (or suspected cause) of deficiency has been addressed. If stopping treatment, advise the person to return if symptoms worsen, reappear, or new symptoms appear.

At follow-up appointments for people receiving intramuscular vitamin B12 replacement:

  • Do not repeat the initial diagnostic test

  • If there are new or worsening symptoms, or if symptoms have not sufficiently improved, increase the frequency of injections if needed (in line with the summary of product characteristics), consider alternative diagnoses, and agree a date for reassessment of symptoms

  • If symptoms are no longer present or have improved:

    • Continue intramuscular injections and agree a next follow-up date if the cause of deficiency is either reversible but has not been addressed, or is unknown

    • If the cause, or suspected cause, of deficiency has been resolved, consider stopping or reducing the frequency of intramuscular injections and advise the person to return if symptoms worsen, reappear, or new symptoms appear

  • If an irreversible cause of B12 deficiency is confirmed or suspected, continue lifelong intramuscular injections, even if symptoms have improved or are no longer present. Advise to return if symptoms worsen, reappear, or new symptoms appear.

Monitoring for gastric cancer

At follow up, consider that people with autoimmune gastritis are at higher risk of developing gastric neuroendocrine tumours and may also be at higher risk of developing gastric adenocarcinoma. If the person has suspected or confirmed autoimmune gastritis and new, or worsening, upper gastrointestinal symptoms (e.g., dyspepsia, nausea or vomiting):

  • Consider referral for a gastrointestinal endoscopyand

  • Follow the recommendations on upper gastrointestinal tract cancers in the NICE guideline Suspected cancer: recognition and referral (NG12).

© NICE (2024) All rights reserved. Subject to Notice of rights NICE guidance is prepared for the National Health Service in England https://www.nice.org.uk/terms-and-conditions#notice-of-rights. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.

Link para a orientação do NICE

Vitamin B12 deficiency in over 16s: diagnosis and management (NG239) March 2024. https://www.nice.org.uk/guidance/ng239

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