Macrocytic anemia: B12 & folate

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Macrocytic anemia B12 folate
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Macrocytosis
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Practical approach to Macrocytosis

• History for alcohol, liver
• CBC and blood film for evidence of marrow disease
• Reticulocyte count
• B12/Folate levels
• Liver function, TSH
• Bone marrow exam if cause in doubt and you really
  want to know

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Low HbAnemia MCV
Lowmicrocytic
Highmacrocytic
Normalnormocytic
Ferritin
Measure B12 folate
Fe deficient
Fe normal
Low - Establish cause
Normal
Establish cause
Obvious cause
Cause not obvious Consider bone marrow
Anemia of chronic disease or hemoglobinopathy
Reticulocyte count
low
Anemia of chronic disease Renal failure Marrow
failure
Hemolysis or blood loss
high
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Vitamin B12 and folate

• All you need to know is contained in the
  following list

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• Both vitamin B12 and folate deficiency cause an
  identical megaloblastic anemia
• Vitamin B12 deficiency causes demyelination in
  the spinal cord and peripheral nerves
• It takes about 3 months to run out of folic acid,
  and 3 years to run out of vitamin B12
• Folate is in meat and vegetables (foliage) and is
  absorbed from the jejunum
• Vitamin B12 is only in foods of animal origin
  its absorption from the terminal ileum requires a
  specific binding protein called intrinsic factor
• Folate deficiency results from poor diet,
  malabsorption or increased requirements
• Vitamin B12 deficiency is commonly the result of
  Pernicious Anemia
• Pernicious Anemia results from an autoimmune
  attack on gastric parietal cells causing
  achlorhydria and Intrinsic Factor deficiency
• Low vitamin B12 levels are common in the elderly
  and usually do not cause anemia they should be
  managed with oral vitamin B12 replacement
• Deficiency of vitamin B12 and folic acid can be
  diagnosed by measuring serum levels homocysteine
  and methylmalonic acid levels may help
• Folate can be replaced orally. Vitamin B12 is
  traditionally given parenterally, but high dose
  oral therapy also works for Pernicious Anemia
• Increasing dietary folate intake in a population
  lowers its average level of serum homocysteine
  the daily dose for a maximum effect is 400 mcg
• Neural tube defects can be prevented by using
  folate supplements in women intending to become
  pregnant

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Biochemical Introduction
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• Both vitamin B12 and folate deficiency cause an
  identical megaloblastic anemia

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Normal
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oval macrocytes
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hypersegmented polymorph
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Normal marrow cells
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Normal marrow cells
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Megaloblastic marrow cells
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Megaloblastic marrow cells
giant metamyelocyte
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• 2. Vitamin B12 deficiency causes demyelination in
  the spinal cord and peripheral nerves

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• It takes about 3 months to run out of folic acid,
  and 3 years to run out of vitamin B12
• Folate is in meat and vegetables (foliage) and is
  absorbed from the jejunum

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Louis Sullivan (b. 1933)
Victor Herbert 1927-2002
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• Vitamin B12 is only in foods of animal origin
  its absorption from the terminal ileum requires a
  specific binding protein called intrinsic factor

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William Murphy 1892-1987
George R Minot 1885-1950
George H Whipple 1878-1976
The Nobel Prize in Physiology or Medicine 1934
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Blood, 1948, 3 (1). 8-21.
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Castle, who slept in a room next door to the
Thorndike ward kitchen, resolutely fed himself
300 grams of raw beef patties every morning while
in fasting state and after one hour induced
regurgitation by pharyngeal stimulation. The
captured semiliquid contents were adjusted to pH
2.5 to 3.5 with HCl and incubated for six hours
at body temperature, after which the liquefied
material was passed through a fine sieve and
neutralized before introduction via Rehfuss tube
into the stomach of the unwitting patient.
Patients who were unresponsive to beef muscle
alone (or to gastric juice alone) showed brisk
reticulocyte responses when this sour admixture
of predigested beef muscle was administered.
Observations on the etiologic relationship of
achylia gastrica to pernicious anemia. I. The
effect of the administration to patients with
pernicious anemia of beef muscle after incubation
with normal human gastric juice. Am. J. Med. Sci.
1929, 178748-63.
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• Folate deficiency results from poor diet,
  malabsorption or increased requirements

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• Vitamin B12 deficiency is commonly the result of
  Pernicious Anemia
• Pernicious Anemia results from an autoimmune
  attack on gastric parietal cells causing
  achlorhydria and Intrinsic Factor deficiency

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Other causes of Vitamin B12 deficiency

• Elderly persons ("food vitamin B12
  malabsorption")
• Inadequate intake
• vegans
• Absorption defects
• Congenital
• Gastrectomy
• Bowel abnormalities
• blind loop syndrome, tropical sprue, fish tapeworm

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• Low vitamin B12 levels are common in the elderly
  and usually do not cause anemia they should be
  managed with oral vitamin B12 replacement

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• Deficiency of vitamin B12 and folic acid can be
  diagnosed by measuring serum levels homocysteine
  and methylmalonic acid levels may help

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• Folate can be replaced orally. Vitamin B12 is
  traditionally given parenterally, but high dose
  oral therapy also works for Pernicious Anemia

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• Increasing dietary folate intake in a population
  lowers its average level of serum homocysteine
  the daily dose for a maximum effect is 400 mcg

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• Neural tube defects can be prevented by using
  folate supplements in women intending to become
  pregnant

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