RE: B12 Deficiency protocols

[Guest guest]

For those of you who are

interested:

Protocol for excluding B12

deficiency (Megaloblastic anemia/ Pernicious Anaemia) from adult and child

patient presentation

Relevance

This

protocol is relevant to all diagnosing clinicians, ie GPs and Nurses. HCAs and

other staff should be aware of the possible ‘presenting symptoms’

and suggest that patients see a diagnosing clinician for further investigation.

Presenting Symptoms

If a

patient presents with Tiredness, depression, hair loss, pins and needles, numbness in

hands or feet, tremors and palsies, palpitations, recurrent headache or

dizziness, B12 deficiency should be

considered.

Beginning a diagnosis –

presenting to GP/ Nurse

Using

Appendix A –1 Minute Health Check – If B12 deficiency is suspected

order a blood test for FBC, Serum vitamin B12, Folic Acid, TSH, U+Es, LFT, Glucose

and other tests you feel are required for symptoms/exclusion/ differential

diagnosis.

Once Blood results are

available

If the

serum B12 level is below 180ng/L (or local laboratory threshold) then staff

should make a 15 minute appointment with the GP or nurse who requested the

blood test. This meeting may reduce to 10 minutes length once Doctors and

Nurses are familiar with the process. on’s “Principles of

Internal Medicine” 16th Ed indicates that with signs and symptoms indicative of B12

deficiency <180ng/L or <200ng/L Clinically significant/ severe B12

deficiency

200-300

Moderate deficiency >300 “Subtle” (subnormal/normal B12 but with

signs & symptoms)

­ Based on on’s “Principles

of Internal Medicine” 16 ed 2005 p606

­ Compare with Lab

specifications from Swindon & Marlborough NHS Trust (see accompanying document

“Observational analysis”)

Therapeutic Trial: if the patient is diagnosed as moderate or subtle

deficiency (>180ng/L with signs and symptoms, other autoimmune condition or

family history) then they should be clinically reviewed every 4 weeks until you

reach a clinical decision whether to commence treatment – even when the

B12 level does not drop below 180ng/L. A deterioration of condition

demonstrated by signs and symptoms is sufficient to commence a therapeutic

trial.

Prophylactic treatment should be given (regardless of borderline blood serum B12)

following Gastro- Intestinal (GI) surgery, and for patients with sudden onset

of paralysis, blindness, psychosis, Crohns colitis, early dementia etc, see

below. B12 deficiency: Treatment Protocol 2

Other Actions to Take

· If clinical depression

is suspected – complete PHQ9 and treat/refer as appropriate

· Neurological

manifestation – neurological examination and refer to neurologist for

further investigation

· Provisional diagnosis of

any other condition – refer to appropriate

Treatment Schedule –

BNF (British National Formulary) Guideline

“9.1.2 Drugs used

in megaloblastic anaemias” (Sept 2010) and

suggested variations

Before

treatment starts, patients should agree to B12 replacement therapy by signing

and dating the appropriate consent form.

Megaloblastic anaemia/

Pernicious Anaemia B12 deficiency with neuro-psychiatric signs and symptoms,

with or without anaemia or macrocytosis, a multi-system, poly-glandular,

multi-point poisonous syndrome.

Hydroxocobalamin1 by

intramuscular injection: Pernicious Anaemia (B12 deficiency) and other macrocytic anaemias

without neurological involvement.

Initially

1mg 3 times a week for 2 weeks then 1mg every 3 months

*Clinically

review every 2 months with or without serum B12 and if clinically indicated increase

the frequency to every 2 months or every month

Pernicious Anaemia (B12 deficiency)

with neurological signs and symptoms.

Initially 1mg on alternate

days

until no further improvement (maximum reversal of neuro-psychiatric signs and

symptoms are achieved), then 1mg every 2 months.

*Clinically

review every 2 months with or without serum B12 and if clinically indicated

increase the frequency to every month or more frequently

Prophylaxis of vitamin B12 deficiency

In the

following instances B12 replacement therapy should be instituted as a

prophylactic measure even when the blood serum B12 is higher than the local

laboratory threshold (>180ng/L or >200ng/L):

1- Specific medical

history renal imbalance, diabetes, >65

years old, or following GI surgery, Crohn’s

colitis,

early onset dementia: initial loading doses followed by 1mg every 1, 2 or 3

months

2- Moderate/ subtle

B12 deficiency with mild signs & symptoms: initially use oral (OC2) B12 1mg per day. The patient’s

blood serum B12 should rise. If the patient’s signs and symptoms do not respond

then review and consider injections (SC/IM) of hydroxocobalamin on the same

basis as for

Pernicious

Anaemia.

3- Moderate/ subtle

B12 deficiency with severe signs & symptoms: patient presenting with strong family history, presence of

other auto-immune conditions, major signs and symptoms which could become

irreversible if treatment is not commenced urgently eg optic neuritis/

neuropathy, sudden

1 methylcobalamin

is used in USA, Canada, India, Japan and other countries. Pharmacists in Wales

also report that they can prescribe methylcobalamin. Methylcobalamin is

considered superior to hydroxocobalamin by many people because it is one of the

natural body forms of B12

2 OC – Over

the Counter. B12 can be purchased as oral lozenges from health food shops and

the internet. Use methylcobalamin for preference

B12

deficiency: Treatment Protocol 3

onset

blindness, subacute combined degeneration, ME, CFS, MS-like

presentation,

single limb paralysis, sudden loss of muscle mass (Motor

Neurone

Disease-like presentation), non-epileptic seizures, dysphagia,

Bell’s

Palsy/ Ramsey Hunt syndrome, Parkinson’s like presentation,

dementia,

total alopecia, migrainous headache, temporal arteritis,

recurrent

miscarriages, dysfunctional uterine bleeding, or psychosis:

initial

loading dose followed by 1mg every 1-3 months

Note:

treatment should be tailored to patient need; some people need injections more

frequently than

once

per month.

Therapeutic Trial should be used where B12 deficiency is suspected because of

signs and symptoms, but

B12

deficiency is subtle or subclinical on the basis of blood serum results. 1mg IM

or SC (hydroxocobalamin

or

methylcobalamin) should be given alternate days for 2 – 3 weeks (6 to 9

doses) followed by 1mg IM or

SC3 per week

for 3 months. Signs and symptoms should be monitored, and frequency varied if

required. If

there

is no improvement in signs and symptoms after 3 months (13 weeks) then B12

deficiency can be

excluded.

A therapeutic trial will not interact with other medication given and other

treatment can be

started

at the same time.

Cyanide poisoning (victims of smoke inhalation who show signs of significant

cyanide poisoning)

hydroxocobalamin

(or methylcobalamin in some countries) the usual dose is 5g (or 70mg/kg in

children) by

intravenous

infusion, given once or twice according to severity.

NOTE

THAT cyanocobalamin is licensed for 1mg IM injection monthly; because of

reduced retention in the

body

in comparison to hydroxocobalamin and methyl-cobalamin (not licensed).

Cyanocobalamin is

excreted

by the kidney preferentially which is why Cobalamin is used to treat cyanide

poisoning.

Nitrous oxide anaesthesia. Nitrous oxide inactivates Vitamin B12 in the body

including brain cells.

Therefore

a B12 deficient patient (or her GP) should alert the surgeon and anaesthetist

so that an

alternative

anaesthetic agent will be used during surgery.

Mother & Foetus,

Neonate, Child

B12 deficiency:

prevention, early diagnosis and treatment

An

undiagnosed, untreated B12 deficient mother receiving only folic acid

supplement could deliver her

child

with neuromuscular damage, sub-acute combined degeneration of the spinal cord,

congenital

abnormalities,

tumours including brain damage and spina bifida. This can be avoided with B12

replacement

before

and during pregnancy (treat as for PA with neurological signs and symptoms).

The

neonate 0 – 1 month born to an untreated B12 deficient mother should

receive intensive IV B12

replacement

treatment in the hospital neonatal department.

Child 1 month – 13

years

If an

untreated B12 deficient mother opts to breast feed, mother and infant will

require B12 replacement

and regular

monitoring as per BNF guidelines. Please note, baby milk powder fortified with

vitamin B12

may

not be sufficient to correct the moderate to severe deficiency in a new-born.

A

child, whether born to a known B12 deficient mother or not, who presents with

delayed development,

hyper

activity, behavioural problems, dyspraxia, learning disability, autistic

spectrum disorder like

presentation,

should initially be screened by blood test, to exclude B12 deficiency,

underactive thyroid,

inborn

errors of metabolism, and any other condition suspected.

3 Injections

Intra-Muscular (IM, into the muscle of the shoulder or thigh) or Sub Cutaneous

(SC, stomach, buttock etc).

IM injections will be released into the blood more quickly giving

faster effects but lasting less time, whereas injections

into fatty tissue will be released more gradually

B12

deficiency: Treatment Protocol 4

Treatment

as per BNF guidelines for children. Review the signs and symptoms

and

vary the frequency according to the child’s needs (following the loading

doses

of alternate day injections); 1mg weekly, fortnightly, monthly, 2 monthly

or 3

monthly.

When

required, refer to appropriate paediatric speciality.

Cessation of treatment

In

most cases, treatment should continue for life. Treatment should be varied as

follows:

· If the patient shows

signs of improvement or is stable for 2 years, then the frequency of injections

can be

extended from monthly to every 2 months, or from every 2 months to every 3

months

· If the patient suffers

symptoms before the next scheduled injection, then the GP should consider

injections

closer together to minimise suffering

· Blood serum B12 is not

considered a good measure of the effectiveness of injections,; relief from

signs

and symptoms is the best measure. It should be noted that the majority of B12

in blood

serum

is in the inactive form, and that the serum B12 test measures all forms of

Cobalamin

including

the less biologically active cyanocobalamin form.

Dr ph Chandy

GP, Shinwell

Medical Centre, Horden, Co Durham

Hugo Minney, PhD

B12 deficiency Patient Support

Group