the consequences of misdiagnosed b12 deficiencyantiageingconference.com/ppt/pacholok12.pdf · the...
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The Consequences of Misdiagnosed B12 Deficiency
Is it aging or is it B12 deficiency?
Sally Pacholok, RN, BSN
The Consequences ofMisdiagnosedB12 Deficiency
Is it aging or is itB12 deficiency?
Sally Pacholok, RN, BSN
The Consequences of Misdiagnosed B12 Deficiency
Is it aging or is it B12 deficiency?
Sally Pacholok, RN, BSN
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Cobalamin (B12) deficiency Cobalamin (B12) deficiency Cobalamin (B12) deficiency
• Ignored• Misunderstood
• Costly epidemic
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Why is B12 deficiency an epidemic?Why is B12 deficiency an epidemic?Why is B12 deficiency an epidemic?
1. Severe knowledge deficit.
2. Poor or absent screening in symptomatic & at‐risk patients.
3. Current range for “normal” serum B12extends far too low.
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Why is B12 def. an epidemic?Why is B12 def. an epidemic?Why is B12 def. an epidemic?
4. Not using other available tests to aid in diagnosis.
5. Waiting for macrocytic anemia to present.
6. Historic name “pernicious anemia” misleading.
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Why is B12 def. an epidemic?Why is B12 def. an epidemic?Why is B12 def. an epidemic?
7. S/S mimic other disease processes.
8. S/S commonly mistaken for normal signs of aging.
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IncidenceIncidenceIncidence
Affects 48 million Americans (16%).1
• Others report B12
deficiency to affect 25% (77 million) Americans.2
1. National Health & Nutritional Examination Surveys 1999 to 2002.
2. Dharmarajan, T.S., Norkus, E.P. Approaches to vitamin B12 deficiency: Early treatment may prevent devastating complications. Post‐graduate Medicine 2001;110(1): 99‐105.
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Incidence B12
def.—U.S. older adults
• 15%‐25% (6‐10 million)
• Hospitalized & nursing home pts
30% to 40% (12‐16 million)
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True incidence is much higherTrue incidence is much higherTrue incidence is much higher
• Patients begin experiencing neurologic symptoms B12: 200‐400 pg/ml.
• B12: 200‐300pg/ml
(35%) 86.1 million.
• Framingham study40% age 26‐83 B12: 200‐300pg/ml.
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What is cobalamin—vitamin B12?What is cobalamin—vitamin B12?What is cobalamin—vitamin B12?
• Brain & nervous system
• Production of neurotransmitters & phospholipids
• Cognitive function
• Cell division & cell reproduction
• Chromosomal replication
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Vitamin B12Vitamin B12Vitamin B12
• Development of RBCs
• Prevent anemia
• Normal growth & development
• Prevention of cardiovascular disease
• Protects against cancers
• Cofactor in enzymatic pathways
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B12 deficiency affects every body system
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B12 is critical for our nervous system
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Myelin sheathMyelin sheathMyelin sheath
• B12 deficiency initially attacks the myelin sheath.
• Left untreated, it affects the entire nerve cell.
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Untreated B12 deficiency causes:
1. Peripheral neuropathy
2. Spinal cord demyelination
3. Spinal cord degeneration
4. Brain atrophy
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B12 naturally found in animal foods B12 naturally found in animal foodsB12 naturally found in animal foods
• organ meats
• red meat
• shell‐fish
• fish
• poultry
• eggs
• dairy products
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History HistoryHistory
Prior to discovery of B12—DEATH was inevitable.
1872: Term "pernicious anemia“ coined by German physician Anton Biermer.
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Why Hx is critical today
Interchangeably use the term PA for B12 deficiency.
Kept name (PA) for historical purposes.
Historic name is confusing today’s physician.
Why Hx is critical todayWhy Hx is critical today
Interchangeably use the term PA for B12 deficiency.
Kept name (PA) for historical purposes.
Historic name is confusing today’s physician.
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Macrocytosis infrequent & late signMacrocytosis infrequent & late signMacrocytosis infrequent & late sign
Folic acid therapy
1998 FDA: Fortified grain & cereal
Co‐existing anemias: Iron deficiency, sickle cell anemia, thalassemia.
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Unlike other vitaminsUnlike other vitaminsUnlike other vitamins
Vitamin B12 must follow a complex pathway of several steps for proper absorption.
A roadblock in any part of this pathway can cause malabsorption & subsequent deficiency.
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Vitamin B12 has a complicated metabolic process Vitamin B12 has a complicated metabolic processVitamin B12 has a complicated metabolic process
1. Salivary glands: R‐protein
2. Stomach: HCl, pepsin, IF
3. Small intestine: R‐binders—ferry B12 into the small intestine.
4. Pancreatic enzymes: carry B12 to the ileum.
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5. Ileum:
Receptors grab onto the
B12‐IF complex, pulling it
into bloodstream.
6. Bloodstream:
Protein (TC II), carries and
transports B12
to various
cells of the body—liver.
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Several causes of B12 deficiency
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N2O inactivates vitamin B12Causes its harmful effects by irreversibly oxidizing the cobalt ion of vitamin B12 from the +1 to the +3 state.
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N2O is contraindicated in the B12
deficient patient
• 1956:
Discovery of N2O
toxicity caused B12
deficiency.
• 1978:
Effects on the CNS
of
N2
O use were discovered.
• Critical to rule out B12
deficiency pre‐op.
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Neurologic signs & symptomsNeurologic signs & symptomsNeurologic signs & symptoms
• Paresthesias
• Weakness—legs, arms, trunk
• Unsteady/abnormal gait
• Balance problems
• Difficulty walking
• Dizziness
• Restless legs
• Tremor
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• Forgetfulness
• Confusion
• Dementia
• Impaired vibration
• Abnormal reflexes
• Impotence
• Urinary or fecal
incontinence
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B12 is critical for CNS & PNSB12 is critical for CNS & PNSB12 is critical for CNS & PNS
• CT & MRI scans show demyelination from late diagnosis.
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Consequences of Misdiagnosed B12 Deficiency
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Psychiatric signs & symptoms Psychiatric signs & symptomsPsychiatric signs & symptoms
• Depression
• Irritability
• Paranoia
• Mania
• Hallucinations
• Psychosis
• Violent behavior
• Personality changes
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Blood signs Blood signs Blood signs
Hematologic signs:Hematologic signs:Hematologic signs:
• Anemia
• Leukopenia
• Thrombocytopenia
• Macrocytosis
• Hypersegmented neutrophils
• Elevated RDW
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B12 deficiency causes anemia.B12 deficiency causes anemia.B12 deficiency causes anemia.
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Critical cofactor for twoenzymatic pathways
Critical cofactor for twoenzymatic pathways
Critical cofactor for twoenzymatic pathways
1. Metabolism of homocysteine Metabolism of of ofhomocysteine
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Functional folate deficiency
CONVERSION OF FOLATE
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2nd Enzymatic Pathway2nd Enzymatic Pathway
2. Metabolism of methylmalonic acid
2nd Enzymatic Pathway
Metabolism ofmethylmalonic acid
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What are the tests?What are the tests?What are the tests?
• B12
• Methylmalonic acid
• Homocysteine
• Holotranscobalamin II(Measures 1 of the blood binding proteins used to transport B12)
Deficiencies start to appear in CSF when B12 < 550 pg/ml.
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Elevated homocysteine Elevated homocysteine Elevated homocysteine
Stroke (CVA)
Coronary artery disease
Heart attack (MI)
Deep vein thrombosis
Pulmonary embolism
Peripheral vascular disease
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27 y/o M: Univ. Chicago Medical Center
Melhem A, Desai A, Hofmann MA. Acute myocardial infarction and pulmonary embolism in a young man with pernicious anemia—induced severe hyperhomocystinemia. Thrombosis Journal 2009 May 13; 7:5.
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Who needs testing?
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Screen following patients:
• Neurologic symptoms
• Mental status changes
• Dementia
• Psychiatric disorders
• GI disorders/surgeries
• Anemia
• Age 60 or >
• Cancer patients
• Diabetics
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Screen following patients:
• Vegetarian diet
• Autoimmune disorders
• Developmental delay
• Autism spectrum
• N2O administration
• Specific medications
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B12 deficiency mimics:B12 deficiency mimics:B12 deficiency mimics:
• Alzheimer’s disease
• MS
• Parkinson’s disease
• Essential Tremor
• Vertigo
• Depression
• Mental illness
• Diabetic neuropathy
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B12 deficiency mimics:B12 deficiency mimics:B12 deficiency mimics:
• CFS
• Fibromyalgia
• RLS
• Chronic pain disorder
• Radiculopathy
• Developmental delay
• Autism
• Other anemias
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Are older adults at high risk for B12 deficiency?
Are older adults at high risk forB12 deficiency?
Are older adults at high risk for B12 deficiency?
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YES!YES!YES!
• Poor stomach acid
• Medications
• Bacterial overgrowth SI
• GI surgeries
• Chemotherapy, radiation
• Malnutrition
• Preexisting diseases
• Dental—surgical procedures N2O use
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Seniors high risk for misdiagnosis.
• Difficulty explaining
symptoms
• Minimizing symptoms
• Poverty
• Mobility limitations
• Already have a Dx
explaining S/S
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Common S/S of older adults— & presenting to ER
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Share EXACT S/S of B12 deficiency
Share EXACTS/S of B12 deficiency
Share EXACT S/S of B12 deficiency
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What does B12 deficiency frequently causein older adults?
What does B12 deficiency frequently causein older adults?
What does B12 deficiency frequently cause in older adults?
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Falls!Falls!Falls!
• Leading cause of death & disability resulting from injury in pts >65.
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Age 65 and older
• Every 18 seconds, older‐adult treated in ED for a fall.
• Every 35 min. a senior dies following a fall.
• 1 in 3 seniors fall each year.
• 1.8 million seniors Txed in ED for nonfatal injuries from falls.
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B12 deficiency is ignored in psychiatric and dementia patients, despite century of documentation.
“Variety of mental changes seen, ranging from depression to paranoid states, and, most important, progressive dementia with impairment of both memoryand cognitive function.”
“Demyelination may be found in the cerebral white matter of the brain and in the optic nerves.”
Neurology & General Medicine, 3rd Edition (2001) Cobalamin Deficiency pages 202‐204.
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Neurology. 2008 Sept 9:71(11):826‐32.
Subjects whose B12 levels were in the lowest 1/3were found to be at 6 times > risk of brain deterioration than those whose B12 levels were in the top 2/3s.
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Typical attitude:
Chief of Geriatrics at U of M Detroit Free Press (3/28/06):
“The center doesn’t routinely test for B12 deficiency unless an elderly person is malnourished. Testing people with slightly low B12 levels or who have memory loss is controversial and not cost‐effective.”
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This patient needs testing.
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Nursing home & assisted living centers
• July 2007: Community service
• Local assisted living residence: 87 seniors consented to screening using urinary MMA.
• Results 19% B12 deficient.
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Undiagnosed B12 deficiency causes:Undiagnosed B12 deficiency causes:
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TreatmentTreatmentTreatment
B12 Maintenance Dose
Injections (IM, SC) 1,000 mcg q 1‐4 weeks
Sublingual 2,000—5,000 mcg daily
Oral 2,000 mcg daily
Intranasal 500 mcg weekly
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The 10 cent secretThe 10 cent secretThe 10 cent secret
• For < 10 cents/day—treat B12 deficiency for an entire year!
$36 ÷ 365 days = 0.098
Injectable B12Hydroxocoblamin• 1,000 mcg/ml
1ml IM—SC qd or qod x 6• 1ml q 2 wks next 12 months • $36.00 (cost/yr)
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ED witness to B12
deficiency epidemic
• Treat everyone—
neonates to geriatrics
• Not limited to group of
pts regarding disease,
body system, age, or sex.
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As we look over these patients’ records…
Obvious battery of tests.
We don’t see evidence that B12 def. included in diagnostic work up—even when pt greatly symptomatic or high risk.
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CDCL & CDR Score (1999)CDCL & CDR Score (1999)CDCL & CDR Score (1999)
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Cobalamin Deficiency Criteria List (CDCL)
I. NEUROLOGIC MANIFESTATIONS
(+2)• Numbness, tingling (including Dx of neuropathy)• Weakness of legs, arms, or trunk• Unsteady, abnormal gait or balance problems, • including difficulty ambulating or near falls• Dizziness or light‐headedness• Tremor (including Dx of Parkinson’s)• Restless legs or Dx of restless leg syndrome• Visual disturbances• Poor concentration or foggy thinking• Forgetfulness, memory loss or (Hx of
dementia/Alzheimer’s)• Mental status changes• Impotence, erectile dysfunction• Urinary or fecal incontinence• Impaired vibration, position sense• Abnormal reflexes• Developmental delay (including Dx of autism)
II. PSYCHIATRIC MANIFESTATIONS (+2)• Depression, suicidal ideations, post‐partum depression,
Rx of antidepressants or history of any other psychiatric
illness or Rx of psychiatric meds• Irritability, anxiety• Paranoia• Mania• Hallucinations• Psychosis• Violent behavior• Personality changes
III. GASTROINTESTINAL RISK (+2)• Decreased stomach acid or atrophic gastritis• Gastric stasis or gastroparesis • Helicobacter pylori• GERD or ulcer disease• Gastrectomy (partial or complete)• Ileal resection (partial or complete)• Gastric bypass or bariatric surgery • Malabsorption syndromes • Crohn’s disease, IBD, IBS, celiac disease (gluten
enteropathy)• Chronic pancreatitis, pancreatic exocrine insufficiency• Bacterial overgrowth (small bowel)• Fish tapeworm• Alcoholism• Malnutrition or eating disorders • (bulimia, anorexia)• Advanced liver disease• Zollinger‐Ellison syndrome
IV. HEMATOLOGIC MANIFESTATIONS (+2)• Anemia • Macrocytosis• Microcytosis• Hypersegmented neutrophils• Anisocytosis (elevated RDW)• Leukopenia• Thrombocytopenia
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V. OTHER SIGNS/SYMPTOMS (+1)
• Generalized weakness or fatigue
• Apathy
• Shortness of breath, chest pain, or exertional dyspnea
• Pallor
• Orthostatic hypotension
• Hepatomegaly or splenomegaly
• Loss of appetite/weight loss
• Poor wound healing/ulcer/decubitus
• Cervical dysplasia
• Tinnitus
• Vitiligo
• Glossitis
VI. POPULATION AT RISK (+1)• Age 60 and over • Fall or fall‐related injury in the past year • Vegans, vegetarians, macrobiotic diets • Autoimmune disorders including IDDM and/or thyroid
disorders • Family history of pernicious anemia• Proton pump inhibitor or H2‐blocker use• Metformin use• Nitrous oxide administration or abuse• Multiple sclerosis patients• Cancer patients• Chemotherapy or radiation• Occlusive vascular disorders (MI, CVA, DVT, PE)• On folic acid therapy• Pregnancy• Breast‐feeding• Iron deficiency • Infertility• AIDS patients• Fibromyalgia or chronic fatigue syndrome patients • Chronic renal failure (hemodialysis patients)• Neck/back surgery, or history of spinal stenosis
COBALAMIN DEFICIENCY RISK (CDR) SCORE• Low Risk:
0—1 • Moderate Risk:
2—5 • High Risk:
6 or greater
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2000: Retrospective Study of 302 ED Patients
2000: Retrospective Study of302 ED Patients
2000: Retrospective Study of 302 ED Patients
40/302 (13.2%) < 180 pg/ml or <133 pmol/L
91/302 (30.1%) 181‐350 pg/ml or 134‐258 pmol/L
131/302 (43.3%) < 350 pg/ml or <258 pmol/L
• 34% male 66% female 30% < age 60
Most common presenting complaints: • Falling (with or w/o Fx)• Weakness• Dizziness• Mental status changes• Chest pain• Neurologic deficits
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2000: Results of 302 Patient Study
2000: Results of 302 PatientStudy
2000: Results of 302 Patient Study
• 60% neurologic S/S
• 45% Hx of TIA or CVA
• 33% anemia
• 28% thyroid disorder
• 25% CHF
• 23% psychiatric disorder
• 20% dementia
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302 Patient Study302 Patient Study302 Patient Study
5/40 (12.5%) macrocytic
3/40 (7.5%) microcytic
2/40 (5%) microcytic anemia
1/40 (2.5%) macrocytic anemia
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Case#
AGESEX
B12
pg/mlRBC HGB
gm/dl
HCT%
MCVfl
RDW%
CHIEF COMPLAINT
CDRSCORE
3. 54 F 131 1.37 5.5 15.2 111.2 21.1 unresponsive—
fall
19
• 54 y/o F
• CDR Score 19
•1/40 (2.5%) macrocytic anemia
• Married with 4 children
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OUTCOME
Only patient with classic macrocytic anemia:
• Numerous falls• Unresponsive—GCS 8• CT brain: Subdural hematoma• PRBC’s/platelets• Emergent brain surgery• Poor outcome• Transfer to nursing home• Vegetative state
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TOTAL
2,785 6%<200 pg/ml
< 148 pmol/L
25%200‐350pg/ml
148‐258 pmol/L
31% <350pg/ml
<258 pmol/L
8%350‐400pg/ml
258‐295 pmol/L
39%<400pg/ml
<295 pmol/L
6 Year Retrospective ER Study (2006‐2011)
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Should this patient be tested?Should this patient be tested?Should this patient be tested?
• 74 M (+1)• Fall—
with L hip Fx (+2)• Hx dementia (+2)• Unsteady gait (+2)• Tremor (+2)• PPI (+1)• Metformin (+1)
CDR Score: 11CDR ScoreLow Risk: 0—1 Moderate Risk: 2—5 High Risk: 6 or >
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Should this patient be tested?Should this patient be tested?Should this patient be tested?
• 47 M
• depression (+ 2)
• Zoloft , Prozac
• Suicidal ideations
CDR Score: 2CDR Score
Low Risk: 0—1
Moderate Risk: 2—5
High Risk: 6 or >
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American Journal of Emergency Medicine (2007) 25, 987.e3‐987.e4American Journal of Emergency Medicine (2007) 25, 987.e3‐987.e4American Journal of Emergency Medicine (2007) 25, 987.e3‐987.e4
• 25 y/o F: ED c/o increasing weakness, 6‐month Hx functional decline.
• Workup: by GP/neurologist MRI brain & LS spine, EMG
• ED : HgB—2.9 MCV—89PLT—12 Folate—normal Serum B12—undetectable
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American Journal of Emergency Medicine (2007) 25, 987.e3‐987.e4American Journal of Emergency Medicine (2007) 25, 987.e3‐987.e4American Journal of Emergency Medicine (2007) 25, 987.e3‐987.e4
• Admitted—4 units of PRBCs, began injectable B12.
• Bone marrow biopsy: megaloblastic changes consistent w/severe B12 deficiency.
Post 8 wks: • sensory abnormalities improved• Motor abnormalities unchanged• Continues to use WC.
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Ethical obligation and responsibility.Ethical obligation and responsibility.Ethical obligation and responsibility.
Failure to recognize B12 deficiency as the etiology of: • neurologic disease
• cognitive decline/dementia
• fall‐related trauma
• non‐macrocytic anemia
represent significant extremes of deviation from the Hippocratic Oath: “First do no harm.”
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Failure to follow the Hippocratic Oath
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Failure to follow the Hippocratic Oath
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B12
deficiency can strike
at any age, both genders,
all races and social classes.
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Untreated B12
deficiency results in:
1.
Fall‐related trauma
2.
Psychiatric illness
3.
Hospitalization/rehabilitation
4.
Use of other costly prescribed
medications
5.
Cognitive changes/dementia
6.
Nursing home placement
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Untreated B12
deficiency results in:
7. Debilitating health,
chronic anemia
8. Neurologic injury
9. Disability
10. Poor outcomes
11.
Misdiagnosis
12. Malpractice
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Call for Action!Call for Action!Call for Action!
Raise awareness
Education
Identify victims early
Test symptomatic & at‐risk pts
Develop new protocols
Treat patients in the “gray zone.”
Enlist help
Create B12 Awareness month
Create World‐Wide B12 Awareness Day
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Reeducating the health care community and the public is key.
Reeducating the health care community andthe public is key.
Reeducating the health care community and the public is key.
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Thank you for your attention! www.B12Awareness.org