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Anaemia - B12 and folate deficiency - Coggle Diagram
Anaemia - B12 and folate deficiency
Definition: Deficiency of vitamin B12 or folate are the most frequent causes of megaloblastic anaemia. Anaemia is defined by haemoglobin (Hb) levels: Children 12-14 year 120g/L, Men (>15) Hb < 130g/L, Women (>15) Hb < 120g/L, Pregnant Women Hb < 110 g/L. There is no gold standard test for measuring vitamin B12 deficiency, but the likelihood of deficiency can be determined by measuring serum cobalamin.
Assessment
Symptoms
Indigestion
Loss of appetite
Headache
Palpitations
Dyspnoea
Tachypnoea
Cognitive changes
Visual disturbances
Weakness, lethargy
Signs
Anorexia
Angina (in older people)
Angular cheilosis
Brown pigmentation affecting nail bed and skin creases (not mucous membranes)
Congestive heart failure
Glossitis
Heart murmurs
Liver enlargement
Mild jaundice
Mild pyrexia
Oropharyngeal ulceration
Pallor of mucous membranes or nail beds
Tachycardia
Weight loss
Neurological complications
Muscle weakness
Optic neuropathy
Loss of mental and physical drive
Psychiatric disturbances - mild neurosis to severe dementia
Loss of cutaneous sensation
Symmetrical neuropathy affecting legs more than arms
Urinary or faecal incontinence
Investigations
Measurement of serum cobalamin and folate levels - to determine the cause of anaemia
Additional investigations eg liver function tests, gamma-glutamyl transpeptidase, and/or thyroid function tests - to identify the underlying cause
Full blood count - determine mean cell volume (MCV), haematocrit and haemoglobin levels and blood film to identify megaloblastic anaemia.
Interpreting investigation results
Full Blood Count
The white cell count and platelet count may be reduced if the anaemia is severe.
There may be a low reticulocyte count in relation to the degree of anaemia (usually 1–3%).
A normal MCV does not exclude the need for cobalamin testing, as neurological impairment occurs with a normal MCV in 25% of cases.
A high mean cell volume ([MCV] greater than 100 femtolitres) is indicative of macrocytosis, however, MCV may be normal if there is associated iron deficiency, or if anaemia develops more rapidly over the course of a few weeks.
Blood Film
Hypersegmented neutrophils (more than 5% of neutrophils with five or more lobes, or one or more neutrophils with 6 or more lobes) and the presence of oval macrocytes, may suggest either vitamin B12 or folate deficiency, but their presence is not sensitive or specific in early cobalamin deficiency.
Oval macrocytes, hypersegmented neutrophils and circulating megaloblasts in the blood film, as well as megaloblastic change in the bone marrow, are typical features of clinical cobalamin deficiency.
Vitamin B12 level
Cobalamin levels are not easily correlated with clinical symptoms, although people with cobalamin levels of less than 100 nanograms/L (75 picomol/L) usually have clinical or metabolic evidence of vitamin B12 deficiency.
In the elderly, low serum cobalamin concentrations usually in the range 100–160 nanograms/L may occur in the absence of anaemia or macrocytosis, and clinically significant vitamin B12 deficiency may be present even with cobalamin levels in the normal range.
The clinically normal level for cobalamin is unclear, although it is thought that serum cobalamin of less than 200 nanograms/L (148 picomol/L) is sensitive enough to diagnose 97% of people with vitamin B12 deficiency.
Women taking oral contraceptives may show decreased cobalamin levels because of a decrease in cobalamin carrier protein, however, this may not result in deficiency.
interpret the results of the serum cobalamin test taking into account clinical symptoms, other laboratory findings and the following limitations:
Serum cobalamin levels fall in pregnant women and are less reliable in determining deficiency.
Folate level
Serum folate of less than 7 nanomol/L (3 micrograms/L) is used as a guide to indicate folate deficiency.
However, there is an indeterminate zone with folate levels of 7–10 nanomol/L (3–4.5 micrograms/L), so low folate should be interpreted as suggestive of deficiency and not diagnostic.
If there is a strong clinical suspicion of folate deficiency but normal serum levels, red cell folate can be measured once cobalamin deficiency has been ruled out.
A red cell folate level below 340 nanomol/L (150 micrograms/L) is consistent with clinical folate deficiency in the absence of vitamin B12 deficiency.
Differential Diagnosis
Liver disease - chronic liver disease is associated with anaemia that is mildly macrocyctic
Pregnancy and neonatal period
Haematological abnormalities - myelodysplasia, aplastic anaemia, pure red cell aplasia, plasma protein changes (eg myeloma) and reticulocytosis.
Severe thyroid function anaemia caused by hypothyroidism (often macrocytic). However, MCV falls once thyroxine treatment is started.
Drugs - antimetabolites, such as hydroxycardamide, methotrexate and azathioprine
Smoking
Alcohol is the most frequent cause of a raised mean cell volume (MCV) in the absence of anaemia.
Alcohol - may cause macrocytosis with neither aneamia nor a change in liver function
Confirmed deficiency
The main cause of folate malabsorption is gluten-induced enteropathy
If cobalamin levels are low, check for serum anti-intrinsic factor antibodies
If folate levels are low - assess dietary folic acid intake and if history suggests malabsorption, check for coeliac disease by testing for antiendomysial or antitransglutaminase antibodies (depending on the local laboratory)
Also test people with strong clinical features of B12 deficiency, such as megaloblastic anaemia or subacute combined degeneration of the cord, despite a normal cobalamin level.
Determine if there is an underlying cause for the vitamin B12 or folate deficiency - specialist referral may be required.
Determine whether the person has experienced complications of anaemia, vitamin B12 or folate deficiency.
Refer/Treat the person where appropriate depending on the suspected cause.
Management: B12 Deficiency
Give dietary advice about good sources of vitamin B12 including eggs, foods fortified with B12 such as cereals, meat, milk, diary products and salmon/cod.
Administer Hydroxocobalamin 1mg IM three times weekly for 2 weeks followed by a maintenance dose. If not diet related
Hydroxocobalamin1mg IM 12 weekly for life. Diet related - oral cyanocobalamin tablets 50-150mcg daily between meals or twice yearly hydroxocobalamin injections.
If neurological involvement seek urgent specialist advice
Management: Folate deficiency
Give dietary advise, good sources include: asparagus, broccoli, brown rice, brussels sprouts, chickpeas and peas.
Check B12 levels in all people starting folic acid - as treatment can mask underlying deficiency allowing neurological disease to develop
Prescribe oral folic acid 5mg daily - usually treatment required for 4 months
Management: Referral
Refer to haematologist if cause is uncertain or unclear, malignancy or blood disorder is suspected, the person does not respond to treatment or the MCV is persistently > 105.
Refer to gastroenterologist if malabsorption or IBD is suspected, in pernicious anaemia and GI symptoms, suspicion of GI cancer.
Seek urgent advice with neurological symptoms
Consider dietician if deficiency is thought to be caused by poor diet.