PERNICIOUS

ANEMIA

MODUL HOM - FK USAKTI

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Pernicious Anemia
Epidemiology:
Most common cause of vitamin B12 def.
About 2% of people over 60 have
undiagnosed pernicious anemia
Average age of diagnosis is approx 60.
Under age 30, it is usually associated with
other autoimmune dz.

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Pernicious Anemia
Historical View
First described in 1849 by Thomas Addison
Austin Flint linked that anemia to the stomach
in 1860.
Named pernicious anemia shortly thereafter.
No longer pernicious as pathophysiology
better understood and simple treatments
available.
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Megaloblastic Anemia
Anemia with macrocytic red cells (MCV > 100 fL)
Low-normal absolute reticulocyte count
BM shows intense erythroid hyperplasia w/
abnormal morphology.
Macroovalocytes and occasional megaloblasts
can be seen.
Hypersegmented PMN ( > 5% w/ 5 or more lobes or > 1% w/ 6
or more lobes.)

A result of impaired DNA synthesis due to def. in

Folate and/or vitamin B12 (cobalamin).

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B-12 Physiology
Normal B-12 absorption:
Dietary B-12 binds to Intrinsic Factor (IF)
in gastric juices.
IF-B12 complex taken up by ileal receptor cubilin.
Released into plasma bound to transcobalamine II.
Enters cells through receptor mediated endocytosis
and metabolized into two coenzymes: adenosyl-Cbl
and methyl-Cbl.

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Folate/B12 DNA Synthesis

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Megaloblastic Anemia
Initial work-up
Check serum B-12, folate (serum or red cell), TSH,
Reticulocyte panel, CBC, Fe panel, Neuro exam.
MCV predictive of b-12/folate def.
B-12 level < 200 pg/mL
If serum B-12 and folate levels are equivocal, check
serum HC and MMA levels. In folate def, only HC is
elevated. In B-12 def, both HC and MMA is elevated
Presence of neurological deficits may also indicate B12 def.

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Pernicious Anemia
Clinical Features:
Megaloblastic anemia
Serum B-12 def
Chronic atrophic gastritis
Neurologic manifistations (paresthesias, numbness,

weakness, memory loss, personality changes, ataxia, loss of vibration and

position sense, psychosis megaloblastic madness)

Atrophic glossitis
Achlorhydria (lack of HCl in gastric juice)
Elevated serum bilirubin and LDH reflective of
increased RBC breakdown due to ineffective
erythropiesis.
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Pernicious Anemia
Pathophysiology
Autoantibody to IF
Two types:
Type I blocks attachment of B-12 to IF
Type II blocks B-12-IF complex to ileal receptor

Autoantibody to gastric parietal cells

Directed against the H/K-ATPase on cell membrane
Leads to decline in the amount of parietal cells and IF
production
Leads to chronic atrophic gastritis and gastric atrophy.
Found in 90% of patients with pernicious anemia.
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Pernicious Anemia
Chronic Atrophic Gastritis
Type A (autoimmune):
due to autoantibodies
Involves the fundus and body which contain acid-secreting
parietal cells and spares the antrum which contains gastrinproducing cells. This leads to achlorhydria and high serum
gastrin levels.

Type B:
Involves fundus, body, and antrum
Usually associated with H.pylori infection.

The progression of Type A chronic atrophic gastritis to

gastric atrophy and clinical anemia is likely to span 20
30 years.
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Pernicious Anemia
Schilling Test
Stage I
Give 1mcg of radiolabeled B-12 orally, followed by
1000 mcg of B-12 IM one hour later to flush any
absorbed radiolabeled B-12 from tissues. A 24-hr
urine is collected to determine how much
radiolabeled B-12 is excreted. Normal is 8-35%.

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Pernicious Anemia
Schilling Test
Stage II
Done only if Stage I is abnormal.
Repeat Stage I, except with the addition of added
oral IF which should normalize B-12 absorption but
not intestinal malabsorption.

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Pernicious Anemia
Schilling Test
Many false pos and neg results
Not commonly used
Not readily available in many places
Less sensitive test checking HC and MMA to
detect B-12 def.
Only recommended when anti-IF antibodies
are normal.
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Pernicious Anemia
Treatment
IM B-12 at 1000 mcg daily for one week, then
1000 mcg weekly for one month, then 1000
mcg every month for one year indefinitely.
No harm in overtreatment. Inexpensive,
non-toxic and excess is excreted in urine.

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Pernicious Anemia
Response to Treatment
Reticulocytosis in 3-4 days
Rise in Hb concentration within 10 days and
normalization in 8 weeks as well as correction
of MCV.
Fall of serum LDH levels within 2 days
Hypersegmented PMN disappear in 10-14 days
Must watch closely for severe hypokalemia
during early response due to marked increased
potassium use in hematopoiesis.
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THANKYOU
FOR THE ATTENTION

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