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Noon Conference
Calvin Knapp
11/19/2018
© 2016 Virginia Mason Medical Center 2
Objectives
Vitamin B12 Deficiency
• Review pathophysiology
• Discuss clinical presentation
• Discuss diagnostic tests
• Review illness script
• Discuss treatment
© 2016 Virginia Mason Medical Center
Absorption
3
© 2016 Virginia Mason Medical Center
Pathophysiology
4
© 2016 Virginia Mason Medical Center
Effects on Hematopoiesis
5
• Megaloblastic Changes
• Slowed division cycle
• Slowed nuclear
maturation
• Ineffective
erythropoiesis
• Premature death of
red blood cells
• Apoptosis v.
phagocytosis
© 2016 Virginia Mason Medical Center
Effects on Neurons
6
• Precise mechanism
unknown
• Reduced
methylation of
neuronal proteins?
• Subacute combined
degeneration
© 2016 Virginia Mason Medical Center
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
7
© 2016 Virginia Mason Medical Center
Differential Diagnosis
8
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
© 2016 Virginia Mason Medical Center
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
9
© 2016 Virginia Mason Medical Center
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
10
© 2016 Virginia Mason Medical Center
Illness Scripts
11
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
© 2016 Virginia Mason Medical Center
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
12
© 2016 Virginia Mason Medical Center
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
13
© 2016 Virginia Mason Medical Center
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
14
© 2016 Virginia Mason Medical Center
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
15
© 2016 Virginia Mason Medical Center
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.
16

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  • 2. © 2016 Virginia Mason Medical Center 2 Objectives Vitamin B12 Deficiency • Review pathophysiology • Discuss clinical presentation • Discuss diagnostic tests • Review illness script • Discuss treatment
  • 3. © 2016 Virginia Mason Medical Center Absorption 3
  • 4. © 2016 Virginia Mason Medical Center Pathophysiology 4
  • 5. © 2016 Virginia Mason Medical Center Effects on Hematopoiesis 5 • Megaloblastic Changes • Slowed division cycle • Slowed nuclear maturation • Ineffective erythropoiesis • Premature death of red blood cells • Apoptosis v. phagocytosis
  • 6. © 2016 Virginia Mason Medical Center Effects on Neurons 6 • Precise mechanism unknown • Reduced methylation of neuronal proteins? • Subacute combined degeneration
  • 7. © 2016 Virginia Mason Medical Center 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 7
  • 8. © 2016 Virginia Mason Medical Center Differential Diagnosis 8 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
  • 9. © 2016 Virginia Mason Medical Center 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 9
  • 10. © 2016 Virginia Mason Medical Center 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 10
  • 11. © 2016 Virginia Mason Medical Center Illness Scripts 11 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
  • 12. © 2016 Virginia Mason Medical Center 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 12
  • 13. © 2016 Virginia Mason Medical Center 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 13
  • 14. © 2016 Virginia Mason Medical Center 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 14
  • 15. © 2016 Virginia Mason Medical Center 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 15
  • 16. © 2016 Virginia Mason Medical Center 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. 16