This document summarizes a presentation on vitamin B12 deficiency. It reviews the pathophysiology of B12 deficiency including its effects on hematopoiesis and neurons. The clinical presentation and differential diagnosis are discussed. Diagnostic tests including blood tests and intrinsic factor antibodies are outlined. Treatment options including B12 supplementation through various routes of administration depending on the ability to absorb are described. Illness scripts contrasting different causes of B12 deficiency like pernicious anemia and malabsorption are provided. Two multiple choice practice questions related to B12 deficiency diagnosis and treatment are presented at the end.

1. Noon Conference
Calvin Knapp
11/19/2018

2. © 2016 Virginia Mason Medical Center 2
Objectives
Vitamin B12 Deficiency
• Review pathophysiology
• Discuss clinical presentation
• Discuss diagnostic tests
• Review illness script
• Discuss treatment

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Absorption
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Pathophysiology
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Effects on Hematopoiesis
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• Megaloblastic Changes
• Slowed division cycle
• Slowed nuclear
maturation
• Ineffective
erythropoiesis
• Premature death of
red blood cells
• Apoptosis v.
phagocytosis

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Effects on Neurons
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• Precise mechanism
unknown
• Reduced
methylation of
neuronal proteins?
• Subacute combined
degeneration

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Clinical Presentation
Affected System Symptoms
Hematologic
Anemia, macrocytosis, polysegmented
neutrophils
Dermatologic Jaundice (2/2 RBC breakdown)
Gastrointestinal
Glossitis (diarrhea, abdominal pain depending
on etiology)
Neurologic
Paresthesias, impaired proprioception,
impaired vibratory sense, gait instability
Psychiatric
Depression, irritability, cognitive impairment,
insomnia
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Differential Diagnosis
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right lung nodules and infiltrates
• For macrocytosis
• Folate deficiency
• Hypothyroidism
• MDS
• Heavy alcohol use
• For B12 Deficiency
• Pernicious anemia
• Dietary
• Bariatric surgery
• Drug induced
• Pancreatic insufficiency
• D. latum (Fish tapeworm)
• Small bowel inflammation or dysfunction

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Diagnostic Tests
• CBC with smear
• MCV> 115
• Low retic count
• Serum B12 levels (<200pmol/L)
• Consider folate depending on diet, GI conditions
• MMA/homocysteine
• Only if serum levels borderline
• Intrinsic Factor Antibodies
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Treatments
• Adults
– If adequate absorption
• 1000mcg cyanocobalamin IV qweek until
repleted, then PO q 1-2 months
– If impaired absorption
• IV, then 1000-2000mcg qdaily
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Illness Scripts
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Pernicious anemia Malabsorption of B12 Folate Deficiency
Pathophysiology
Antibodies against
intrinsic factor
Poor uptake of B12 in ileum
Decreased folate intake or
increased cell turnover
Epidemiology More common in women
Bariatric surgery patients
Illeal resection patients
Chronic pancreatitis
Patients with poor nutrition,
pregnant patients, exfoliative
skin diseases
Time course Chronic (5-10 years) Chronic (5-10 years) Subacute (1-3 months)
Clinical
presentation
Anemia, neuropsychiatric
symptoms
Anemia, neuropsychiatric
symptoms
Anemia
Diagnostics
Labs: CBC with smear, B12,
folate, Anti-IF antibodies,
Anti-parietal cell
antibodies (increased risk
chronic atrophic gastritis)
Labs: CBC with smear, B12,
folate, consider workup for
potential malabsorption
etiologies (IBD, celiacs, etc.)
Labs: CBC with smear, B12,
folate
Therapeutics Vitamin B12, EGD Vitamin B12 Folate

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Back to Mr. S …
• Initial coag panel concerning for DIC
• Low platelets, low haptoglobin, elevated LDH, low
fibrinogen
• Likely underlying liver disease
• Elevated T. Bili, INR
• Coagulopathy – likely nutritional
• Thrombocytopenia – likely B12 deficiency,
alcohol use
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Summary
• B12 deficiency causes anemia and can cause
neurpsychiatric symptoms
• Common causes are malabsorption, pernicious
anemia, drug induced
• Need to consider etiology when pursuing further
diagnostic measures
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MCQ #1
A 58 year old female with a history of DM1 presents to your
clinic with fatigue and complaints that her tongue seems to
have enlarged. She read online that this might be because of
B12 deficiency, and started taking 1000mcg of
cyanocobalamin a day one week ago. CBC reveals Hgb 10.3
with an MCV of 118. Vitamin B12 level is 900 pmol/L. Intrinsic
factor antibody testing is negative. What is your next step?
A. Congratulate the patient on her medical acumen and send
her on her way
B. Continue daily B12 supplementation for 1 month and
recheck Vitamin B levels
C. Discontinue vitamin B12 supplementation, recheck Vitamin
B12 and Anti- IF level in 2 weeks
D. Repeat her lab work and get an EGD
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MCQ#2
A 70 year old male presents to your office regarding a new health
trend his grandchildren told him about. He states that over the last
two months he has stopped eating breakfast and lunch and instead
has 2 shots of bourbon when he wakes up, and at midday. The
patient does report some fatigue with this lifestyle change. CBC
demonstrates Hgb 9.9 with MCV of 121. Serum folate is borderline
normal and B12 is within normal limits. What would be the next best
step?
A. Check serum MMA and homocysteine levels, would expect both
to be elevated
B. Check serum MMA and homocysteine levels, would expect MMA
to be elevated
C. Recommend avoiding brown liquor due to the harmful bacteria in
the casks
D. Check serum MMA and homocysteine levels, would expect
homocysteine to be elevated
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References
• Schrier, Stanley L “ Causes and pathophysiology of vitamin
B12 and folate deficiency.” Uptodate. Last updated July
2nd, 2018.
• Schrier, Stanley L “ Clinical manifestations and diagnosis of
vitamin B12 and folate deficiency.” Uptodate. Last updated
August 27th, 2018.
• Schrier, Stanley L “ Treatment of vitamin B12 and folate
deficiencies.” Uptodate. Last updated July 19nd, 2018.
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