Transcript A day in medicine clinic - University of Washington

Jenny Wright, MD
• Present a series of patients typically of those seen in medicine
clinic, highlighting common patient presentations, diagnoses and
management
• Discussion of anemia in both the outpatient and inpatient setting
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51 year old female here today for a preventive health visit.
PMHx: Depression/Anxiety, Paroxysmal SVT
Medications: Atenolol PRN, Estring, Ambien PRN
All: NKDA
Habits: Exercises 30 minutes 5 days a week, diet healthy; EtOH:
2-3 glasses of wine a night, no tob, no IVDU
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What cancer screening should we be considering?
Cervical Cancer
Breast Cancer
Colon Cancer
www.ahrq.gov
• She is in a mutually monogamous relationship and has a history
of normal Pap smears, most recently last year. When will she be
due for repeat cervical cancer screening?
• A. She doesn’t need additional screening unless she has new
partners
• B. A today’s visit
• C. In four years
• D. In two years at which time consider also consider HPV
screening
• Recommendations of the USPSTF:
• Don’t screening younger than age 21.
• Screen women ages 21 to 65 years with cytology (Pap smear) every 3
years or, for women ages 30 to 65 years screen with a combination of
cytology and human papillomavirus (HPV) testing every 5 years.
• Stop screening in women older than age 65 years who have had
adequate prior screening and are not otherwise at high risk.
• Don’t screen women who have had a hysterectomy who do not have
a history of a high-grade precancerous lesion or cervical cancer.
• Do you need to screen a sexually active 19 year old?
• Do you need to screen a women who’s s/p hysterectomy for
menorrhagia d/t fibroids?
• How often do you need to screen a 28 year old female with
HIV disease?
• The USPSTF:
• Biennial screening mammography for women aged 50 to 74 years.
• “The decision to start regular, biennial screening mammography
before the age of 50 years should be an individual one and take
patient context into account, including the patient's values
regarding specific benefits and harms.”
• +/- clinical breast examination (CBE)
• Insufficient evidence to assess the additional benefits and harms of
screening mammography in women 75 years or older.
• Recommend against teaching breast self-examination (BSE).
• The American Cancer Society, AMA, ACOG: Annual screening
beginning at age 40.
• Q: What is the best test to screen for colon cancer?
• The USPSTF recommends:
• screening using fecal occult blood testing, sigmoidoscopy, or
colonoscopy beginning at age 50 years and continuing until age 75
years.
• recommend against routine screening in adults age 76 to 85 years.
There may be considerations that support colorectal cancer screening
in an individual patient.
• recommends against screening for colorectal cancer in adults older
than age 85 years.
• The American College of Gastroenterology: Generally agrees
though states ‘preferred’ strategy is colonoscopy
• A. Current smokers with a 25 pack-year history, beginning at
age 50
• B. No one
• C. Those with a 30 pack year history (current smokers, or those
who quit within the past 15 years), aged 55-80
• D. Current smokers with a family h/o lung cancer, beginning at
age 60
Age to initiate
screening
Age to stop
screening
Frequency of
screening
Cervical
21
65
3-5 (test specific)
Breast
40/50 (USPSTF)
75 (?)
1-2
Colon
50
75-85 (?)
Modality dependent
Lung Cancer, pts
with h/o heavy
tobacco use only
55
80
Annual low dose
chest CT
• Are you concerned about her level of alcohol use – 2-3 glasses
of wine a night?
• Spectrum of unhealthy alcohol use: Risky use → Alcohol abuse
• CAGE questionnaire screening of abuse:
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Cut down
Annoyed/angry.
Guilty.
Eye opener.
• Risky alcohol use:
M > 14 drinks a wk or 4 on one occasion
F > 7 drinks a wk or more than 3 on one occasion
• 74 year old year old
English speaking female
with dementia presents
with several concerns
including a rash. The rash is
located under both
breasts, time course
unclear, has been using
clotrimazole, neosproin
and hydrocortisone. It
doesn't itch or hurt.
http://www.aafp.org/afp/2005/0901/
afp20050901p833-f1.jpg
• Tinea
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Tinea pedis: moccasin or btwn the toes
Tinea corporis: annular, scaly plaque, “ringworm”
Tinea cruris: Men > women, typically spares the scrotum (vs candida)
Tinea versicolor: Malassezia furfur yeast, hyper- or hypo- pigmented
patches
• Can confirm dx with KOH prep of skin scraping
• Candidiasis
• Vivid erythematous rash in intertriginous regions
• A 54 yo male presents
with a one week history
of a painful, mildly itchy
rash under and on the
posterior aspect of his L
arm. He has a history of
eczema and has been
using Clobetasol and
triamcinolone creams on
the rash without
improvement.
• Herpes Simplex Virus
• Primary infection can be severe with systemic symptoms
• Confirm dx with DFA/PCR, serologies rarely helpful
• Herpes Zoster
• Prodrome of pain and burning common
• If first division of trigeminal nerve involved need ophthalmologic evaluation
• Treatment with antiviral, ideally within 24-72 hrs decreases duration and
severity
• Post-herpetic neuralgia: 10-15% of patients, more common in older patients
• Vaccinate! reduces risk of zoster by 50%, or PHN 66%
• Human Papilloma Virus
• Vaccinate!
• 28 yo female with
celebral palsy and
developmental delay
with erythematous, itchy
rash in the bilateral
antecubital fossae. These
developed after pt
repeatedly applied
shower gel to her arms,
thinking it was a
moisturizing lotion.
http://o.quizlet.com/i/VI
H52FPtYT59Acm6A_h6Pw
_m.jpg
• Itchy red rashes
• Contact dermatitis:
• The pattern often gives it away
• Common offenders: poison ivy, nickel, topical antibiotics, hair dye, fragrances
• Atopic dermatitis:
• Typically begins in childhood
• Wrists, anticubital and popliteal fossae
• In chronic cases see lichenification
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Dyshidrotic eczema: intensely pruritic vesicles on hands
Xerotic eczema: dry skin, often seen in winter, lower extremities
Nummular eczema: Itchy coin-shaped patches, favor extremities
Stasis dermatitis: Occurs in the setting of lower extremity edema,
confused with cellulitis
32 year old healthy male
presents with a rash. He
has noted red spots on his
back and abd for the past
few weeks, they are not
itchy or painful.
http://www.primehealthchannel.com/wpcontent/uploads/2011/02.jpg
• Pityriasis rosea:
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typically 10-35 yr pts
occasionally will be pruritic
Herald patch -> multiple small patches on truck
resolves within a few months
• Seborrheic dermatitis:
• Scalp, eyebrows, ears, nasal folds
• more common at HIV and Parkinson’s
• treat with topical azoles or dandruff shampoos, if severe can use topical
steroids
• Psoriasis
• Lichen planus
• 57 yo male with h/o
liver transplant 10 years
ago presents with a
bump on his L cheek, it’s
been present for several
months. It isn’t itchy. It
comes and goes, he
thinks that it’s an ingrown
hair because it’ll bleed a
little then seem to heal.
http://www.newyouthmedicalspa.com/wpcontent/uploads.jpg
• Basal Cell Carcinoma:
• Nodular variant – pearly papules with telangectasia
• Squamous Cell Carcinoma:
• Precancerous lesion is an actinic keratosis (1-5% -> SCC)
• Scaly, crusted papule
• 2-5% risk of metastasis
• Melanoma:
• ABCDE: asymmetry, irregular border, multiple colors, diameter > 6 mm,
evolution over time
• General Population:
• USPSTF: “counsel persons with fair skin who are 10 to 24 years of age
about sun-protective behaviors”
• Behavior change was found with counseling in this age group
• Regular sunscreen use can prevent squamous cell carcinoma, but evidence
is less strong that it can prevent basal cell carcinoma or melanoma
• Transplant population:
• Much higher risk of skin cancer (ex. Liver transplant pts have 100X the risk
of SCC! Skin cancers often more aggressive too)
Ann Intern Med. 1 February 2011;154(3):190-201
• A 30 year old male with
h/o CVID presents with
sinusitis, he is started on
Bactrim. Several days
later he returns to clinic
with a erythematous
area near his lip.
http://www.your-doctor.net/dermatology_atlas/rwx/rwx.jpg
• Wide variety of
dermatologic
manifestations can occur:
• Most common: Morbilliform
drug rash; antibiotics are
common culprits
• Previous case: Fixed drug
eruption: intense dark red
round patch; common
culprits include betalactams, macrolides and
trimethoprim-sulfa)
• Classic “drug rash”
http://www.uptodate.com
Series of pigmented
lesions and rashes with
great pictures
• 66 year old year old male presents for follow up on DM, HTN,
HLD. Labs prior to today’s visit: TC 238/TG 173/HDL 37/ LDL
134.
• What are you going to do now?
General Considerations
• Lipids lowering with statin
medications reduces CV
disease risk in all populations
• Absolute risk reduction is
dependent on patient’s
baseline risk, therefore this is
the first issue to consider
• Therapeutic lifestyle changes
should be recommended to
all patients with
hyperlipidemia
ACC/AHA recommendations
Risk Group
Tx
recommendation
Clinical ASCVD
Hi intensity statin
LDL >190
Hi intensity statin
DM
Mod. intensity statin
10 yr ASCVD risk
>7.5%
Mod-hi intensity
statin
Framingham
Pooled Cohort Equation
Risk Group
Tx
recommendation
Examples
Clinical ASCVD
Hi intensity statin
atorvastatin 80 mg
rosuvastatin 20 mg
LDL >190
Hi intensity statin
Per above
DM
Mod. intensity statin
atorvastatin 10 mg
simvastatin 20-40 mg
lovastatin 40 mg
pravastatin 40 mg
10 yr ASCVD
risk >7.5%
Mod-hi intensity
statin
Per above
• 66 year old year old English speaking male who presents
today for follow up on DM, HTN, HLD. Labs prior to todays visit:
TC 238/TG 173/HDL 37/ LDL 134
• What are you going to do now?
• “diet and exercise”…
Mediterranean Diet Shown to Ward Off Heart Attack
and Stroke!
• CDC recommendation:
• 150 minutes of moderate activity or 75 minutes of vigorous activity a
week + muscle-strengthening activities on 2+ days
• Pedometer use (JAMA 2007;298(19):2296-2304):
• Use is associated with increases in physical activity (+2500 steps a day!)
and mild weight loss (BMI -0.38) and improvement in blood pressure (SBP
-3.8)
• Week one: First wear the pedometer for a week and assess
baseline daily average number of steps.
• Week two: Work to increase daily number of steps by 500.
• Every two weeks increase daily goal by 500 steps.
• Keep doing this up to10,000 steps a day (target level).
• Pearls:
• Baseline LFTs +/- CK recommended
• American College of Cardiology, AHA, and NIH
• Don’t need to follow LFTs
• 2012, the US Food and Drug Administration
• Side effects:
• Statin myopathy – myalgias are common (up to 10%!), rhabdomyolysis
extremely rare
• FDA recently added memory loss of drug labeling though evidence is sparse
• Increased risk of diabetes – effect much smaller than known CV benefit
• JAMA Intern Med 2013;on-line publishing June 3
• Cohort of 46,000+ active and retired military patients; from
this group propensity score matched about 7000 statin users
and non-users
• OR for various severity of musculoskeletal complaints (including
dx of joint sprain, strain, muscle pain) ranged from 1.09-1.19
• NNH ranged from 37-58
• 39 yo female with a h/o migraines presents to discuss
depression. She has a h/o depression and in the past has had
trials of sertraline, citalopram and venlafaxine, all with
significant side effects -- nausea, worsening of her n/v with her
migraines -- and no benefit of her depression symptoms. For the
past 3-4 wks she’s had depressed mood, difficulty with
concentration, desire to sleep all the time/lethargy, anxiety and
inability to manage difficult situations. She is here for
suggestions regarding possible treatment.
• Which of the following in the most effective treatment of mildmoderate depression?
• A. Psychotherapy
• B. SSRIs
• C. TCAs
• D. SNRIs
• E. These are all roughly equally efficacious
PHQ- 9 is helpful
for diagnosis
and assessment
of severity
• Side effects: Minimize by starting at a very low dose and slowly
up-titrating
• Follow up: 1-2 wks (in clinic or by phone)
• Expect to stat seeing improvement in 2-6 wks
• If no improvement by 8 wks consider modifications to therapy
• If treatment with one SSRI doesn’t work what should be the next
medication you try?
• A. Another SSRI
• B. Anything but an SSRI
• C. Add another medication to the SSRI
• Lessons:
• If pt intolerant or
unresponsive to one SSRI
may still have benefit to a
second
• Augmentation with
bupropion (better
tolerated than
augmentation c buspirone)
is also effective
Initial treatment:
Citalopram
Switched to
sertraline,
bupropion,
venlafaxine or CBT
Augmented with
bupropion,
buspirone or CBT
26 year old female with a h/o hypothyroidism
presents to clinic for evaluation after attempting to
donate blood and being was told that she was anemic.
What labs would you order at this visit?
A) Hematocrit
B) CBC, iron, TIBC, and ferritin
C) TSH, CBC, reticulocyte count
D) TSH, CBC, reticulocyte count, peripheral blood
smear, iron, TIBC and ferritin
 Acute blood loss
 Decreased production of RBCs:
decreased erythropoetin (epo)
Normal production of epo but decreased ability to respond to epo
 Destruction of RBCs:
intravascular
extravascular
ideal
Reticulocyte count: this may be reported as the
absolute count (determined by flow cytometry) or the
reticulocyte count as a percentage of the total
erythrocytes – in this case you want to calculate the
reticulocyte index (RI=reticulocyte% x pt’s Hct/45 x
0.5).
If low-normal (absolute count <75,000, RI<2), bone
marrow hypoproliferation: production problems
If high (absolute count >100,000/microL, RI>2), bone
marrow hyperproliferation: hemolytic anemia, acute
blood loss
http://www.uptodate.com.offcampus.lib.washington.edu/online/content/images/H
EME/9131/Polychromatophilia.jpg
ideal
 Peripheral blood smear:
 Offers important additional information regarding the
morphology of the cells that cannot be obtained from other
laboratory data.
 Examples include differentiation between types of hemolytic
anemia, different types of macrocytic anemias.
Microcytic (MCV<81): iron deficiency, thalassemia,
sideroblastic anemia, anemia of chronic disease
Normocytic (MCV 81-98): anemia of chronic disease,
aplastic anemia, bone marrow infiltration, kidney
disease, acute blood loss
Macrocytic (MCV >98): alcohol, B12 deficiency, folate
deficiency, myelodysplasia, drug toxicity,
reticulocytosis, liver disease
26 year old female presenting for evaluation after
attempting to donate blood and being was told that she
was anemic.
 Her labs reveal: TSH 6.3 microIU/mL (high), low reticulocyte
count, Hct 33%, MCV 74, iron 35 (low), TIBC 540 (high), ferritin
14 (low). What do you do next?
 A) treat with oral iron
 B) order a colonoscopy
 C) increase her levothyroxine dose
 D) start oral contraceptive pills
Ferritin can be the most useful single test, though due
to the fact that it is an acute phase reactant, only in
patients without infection/inflammation
All pt’s with ferritin <15 are iron deficient (highly
specific but not sensitive), values >100 essentially rule
out iron deficiency.
Other characteristic iron study results are: elevated
TIBC, low transferrin saturation and low serum iron
level
Progression of change:
hypochromia (decreased MCHC) → microcytosis
(decreased MCV), → anisocytosis (increased RDW)
• Iron deficiency (even without anemia) is associated with restless
leg syndrome, hair loss, and delayed cognitive development in
children
• Anemia may manifest as fatigue, weakness, headache,
irritability
• Pica is the setting of severe deficiency
In severe cases may
have additional physical
exam findings:
Evaluate for cause:
In post-menopausal females and males you have to evaluate
for GI blood loss.
In menstruating females, menses is a common cause.
Treat: Iron replacement can typically be given orally,
ferrous sulfate or gluconate 325 mg, 1-3 times a day.
Ideally pts are treated with TID medication though this is
rarely tolerated
Sulfate salt is cheaper and has more elemental iron but
generally less well tolerated
 Three months later pt returns, still being told she can’t give
blood! Her Hct is 34% and ferritin 15. TSH nl. What do you do
now?
 A) review how she’s taking her medications
 B) transfusion
 C) give it more time
 D) start vitamin C
 Side effects of oral iron replacement lead to low compliance.
Constipation, stomach upset
May have less symptoms if they take it with food (though this decreases
absorption)
 Consider other causes of poor absorption: celiac disease, IBD,
h/o gastrectomy or gastric bypass, taking with an antacid, PPI,
calcium.
 Vitamin C enhances absorption
 Expect Hct to improve within several weeks of therapy though
pts should continue treatment for 6 mo -1 yr, would like to see
ferritin level normalized
 A 68 year-old woman with hypothyroidism and HTN, presents
for evaluation of unintentional weight loss and night sweats.
CBC notable for WBC 11.2, Hct of 32%, MCV 79; TSH nl; CMP
with Na 133, Alb 3.0.
 What is your differential for her anemia and what labs would
you order?
Lab findings:
Hypoproliferative anemia (low reticulocyte count)
Typically a normocytic anemia, though 25% of cases
are microcytic
Classically labs will reveal an normal - elevated
ferritin, and low serum iron and TIBC.
Etiology: multiple contributing factors including
decreased transfer of iron to red blood cells,
decreased response to Epo, decreased Epo release
Treatment: Treat underlying cause
ACD
Fe def.
ACD + Fe def
Serum iron
Low
Low - Very low
(<15 mcg/dL)
Low
TIBC
Low - normal
High nl - high
Normal
Transferrin
saturation
Low
Low -Very low
(<10%)
Low
Ferritin
Normal – high
Low - Very low
(<15 ng/mL)
Low - normal
Serum ferritin is the single best test for iron deficiency – a ferritin <10 is 99%
specific!
Ferritin >100 effectively rules out iron deficiency.
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What is the most common cause of anemia in women?
Iron deficiency
What is the most common cause of anemia in men?
Anemia of chronic disease
• 61 yo female with bipolar disorder, stress incontinence,
obesity and COPD presents with back pain.
• HPI: 6 week h/o low back pain, typically dull, in a
band across the low back though with activity
occasionally sharp and more central in location.
Radiates into the R posterior lower extremity. Worse
with activity. Better with naproxen.
• Are you worried or not worried?
Low Back Pain
Dangerous
Not
dangerous
• What are the “red flag” symptoms for back
pain?
Red Flags
Why would this make you worry about?
Trauma (even minor in the elderly)
Unstable spine
Major and progressive motor or
sensory deficit
Central cord compromise
New-onset bladder or bowel
incontinence or urinary retention
Cauda equina syndrome
Saddle anesthesia, loss of bowel tone
Cauda equina syndrome
H/o cancer, unexplained weight loss,
age > 50
Bone metastasis
H/o IVDU, immunosuppression
Vertebral diskitits/osteomyelitis/epidural abscess
Known osteoporosis, h/o steroid use
Compression fracture
• What is the differential diagnosis of low back pain without red
flag symptoms?
Low Back Pain
Mechanical non-specific LBP
Spondylosis (degenerative disk disease, facet joint arthropathy)
Spinal stenosis
Herniated nucleus pulposus
Spondylolisthesis
Inflammatory spondyloarthropathy
Exam
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VS: BP 136/84 | Pulse 80 | Wt 272 lb
(123.378 kg)
Musculoskeletal: ROM and muscle strength: No
scoliosis or splinting. No spinous process
tenderness. Has pain to palpation in the
paraspinal region bilateral low back. Normal
flexion and extension of the back. Muscle
strength is grossly normal for the lower
extremities.
Sensory exam and Reflexes: Patellar DTRs are
normal bilaterally. Sensation intact to light
touch in the L4 and S1 distributions.
Straight leg raising: Reproduces radiating pain
when R leg raised, no pain when L leg
elevated.
Rational
Spinous process tenderness: Bony etiology
Muscle strength, sensation, reflexes: neurologic
compromise, pattern
Radicular patterns:
• L4 – quadriceps weakness, patellar reflex
diminished, medial foot sensation
• L5 – great toe and ankle dorsiflexion
weakness, no reflex changes
• S1 – great toe and ankle plantar flexion
weakness, Achilles reflex diminished, lateral
foot sensation
Straight leg raise: testing for nerve impingement in
the setting of radicular symptoms
When do you need to test rectal tone?
The straight leg raise
Positive ipsilateral straight leg
raise: Sensitivity>Specificity
Contralateral straight leg raise:
High specificity
Sensitivity and Specificity
• Spin: Highly specific tests are
useful for ruling thing in
• Snout: Highly sensitive tests
are useful in ruling things out
Disease
No disease
+ test
A
B
- test
C
D
Sensitivity = A/(A+C)
Specificity = D/(B+D)
Positive Predictive Value = A/(A+B)
Negative Predictive Value = D/(C+D)
• What if she was 10 years older (71) and presented with back
pain radiating to the bilateral posterior thigh regions, worse
with ambulation, better if she sits down. Physical exam notable
for nl pedal pulses.
• Diagnosis?
• Spinal stenosis:
• Typically presents are bilateral leg pain in elderly patients.
• Psuedoclaudication: pain worse with standing, walking downhill, better
with leaning forward, sitting or lying down
• Back to our patient, 61 yo female with subacute radicular low
back pain. In the setting of acute back pain, what
evaluation/mgmt are you going to propose?
• A. Non-steroidal anti-inflammatory medications and physical
therapy
• B. MRI
• C. Inflammatory markers and plain films
• D. Low dose narcotics and muscle relaxants
• Back to our patient, 61 yo female with subacute low back pain.
In the setting of acute back pain, what evaluation are you
going to do?
• A. A trial of conservative therapy with non-steroidal antiinflammatory medications and physical therapy
• B. MRI -- emergent if risk for acute cord compression - suspect
unstable spine, infection, pt with cauda equina syndrome
• C. Inflammatory markers and plain films -- may be helpful if
suspect malignancy, compression fracture
• D. A trial of conservative therapy with low dose narcotics and
muscle relaxants
Imaging, when and what
Clinical scenario
Immediate imaging
- Xray and ESR
Major risk factors for cancer
- MRI
Concern for spinal infection
Signs of cauda equina
Severe neurologic deficits (multiple levels,
progressive)
Defer imaging after trial of therapy
- Xray +/- ESR
Weak risk factors for cancer
Concern for ankylosing spondylitis
Concern for vertebral comp fx
- MRI
s/s of radiculopathy if considering ESI or
surgery
s/s of spinal stenosis if candidate for
surgery
Ann Intern Med 2011;154:181-189
• How to do you treat it?
• Patient education: “It’s common and the majority of pt’s get
better”
• though 31% continue to have pain at 6 mo and recurrence is common, 2562% within 1-2 yrs
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Avoid bedrest
Medications: NSAIDs, muscle relaxants, acetaminophen
Physical therapy
Heat or ice
• She returns to clinic 8 weeks later without significant
improvement. At this time she describes radicular pain as most
bothersome.
• What do you do now? Interventions:
• Medications: Trial of Gabapentin, TCA
• Epidural steroid injection? Consider for radicular pain not responding to
conservative therapy
• Note, most herniated disk get better on their own
• Surgery – clearly indicated for acute cord compression, results
are mixed for spinal stenosis and persistent nerve root
compression
• You note that she has chronic back pain, she also has a h/o
knee osteoarthritis, HTN and sleep apnea. Her weight is 272
lbs. She has tried to lose weight and been unsuccessful. When
do you consider bariatric surgery?
• Step 1: Calculate and interpret pts BMI
• 25-29.9 kg/m2 = overweight
• ≥ 30 kg/m2, varying degrees of obese
• General Criteria:
• BMI ≥ 40 or ≥ 35 with co-morbidities related to obesity (DM, severe OA,
HTN, sleep apnea)
• Able to tolerate surgery
• Failed to lose weight with conservative interventions
Weight loss counseling
and lipid management
 48 year old homeless female with alcohol dependence presents
to clinic for evaluation of several concerns including fatigue.
Labs are remarkable for: Hct 34%, MCV 110, RI <2 . Her
PMHx is remarkable for rheumatoid arthritis.
 The most likely diagnosis is:
 A. chronic GI blood loss due to gastritis
 B. dietary B12 deficiency
 C. folate deficiency
 D. anemia of chronic disease
In addition to B12 and folate deficiency, causes
include:
Alcohol
Drug toxicity: zidovudine (AZT), hydroxyurea
Hypothyroidism
Liver disease
Hyposplenism
Myelodysplasia
Hemolysis
Be sure to assess reticulocyte count to eval for stress
erythropoiesis
 The smear in a patient with macrocytic anemia is helpful in
identification of megaloblastic changes – macro-ovalocytes and
hypersegmented neutrophils (>5 lobes)
 Etiologies include: B12 deficiency, folate deficiency, drugs that
cause abnl DNA synthesis or folate metabolism, and
myelodysplastic syndromes
Image from Joyce Wipf, MD
Non-megaloblastic
macrocytosis is typical of
liver disease and
hyposplenism, on smear
patients may have large
target cells,
acanthocytes, and
Howell-Jolly bodies.
http://www.uptodate.com.offcampus.lib.washin
gton.edu/online/content/image.do?imageKey=
HEME%2F9127
Found in: Fruits (e.g. citrus, melon, bananas), leafy
green vegetables, and fortified grain products
Causes include:
Alcohol: decreases ability to absorb folate and, frequently
associated c decreased intake of folate rich food
Malabsorption (celiac disease, IBD)
Diseases/conditions associated with rapid cell turnover such
as sickle cell disease*, psoriasis, pregnancy
Medications: phenytoin, methotrexate
* Chronic hemolytic anemia = daily
folate supplementation
The body stores large amounts of B12 therefore
decreased dietary intake rarely lead to deficiency,
typically due to decreased absorption due to
pernicious anemia and intrinsic factor deficiency,
atrophic gastritis or IBD.
Medications to decrease stomach acid can also
contribute to B12 deficiency (PPIs, antacids)
In addition to causing anemia, B12 deficiency can
lead to a metabolic peripheral neuropathy and
neuropsychiatric disease (not the case for folate
deficiency)
• Long term metformin treatment is associated with increased
rates of B12 deficiency, <150 pmol/L, (NNH 13.8 per 4.3 yrs)
and low B12 150-220 pmol/L (NNH 8.9 per 4.3 yrs)
• Clinical outcomes not measured
• If and when to screen remains unclear
de Jager J, Kooy A, Lehert P, et al. Long term treatment
with metformin in patients with type 2 diabetes and risk of
vitamin B-12 deficiency: randomized placebo controlled
trial. BMJ 2010;340:c2181.
 Labs reveal a low folate level and a normal B12 level (450).
You initiate folic acid supplementation with 1 mg po q day.
 As was done here, you always want to assure that pts don’t also
have B12 deficiency prior to treating for folate deficiency, you
may be able to improve a patients anemia but the neurologic
symptoms will progress
 If levels are at the lower limits of normal (200-300), then
consider checking methylmalonic acid and homocysteine levels,
these will be elevated in the case of B12 deficiency
 Should be given orally, IM in rare situations
Oral dosing is 1000 – 2000 mcg po q day
IM dosing is 1000 mcg IM q day x 7 days, then q wk x 4 wks then q
month
A 28 year African American old female presents to clinic
with fatigue. She has a history of cellulitis and just
finished a 14 day course of therapy with Bactrim. TSH
is normal, Hct is 25%, MCV 98. What do you think is
the most likely cause of her anemia?
A. hemolysis
B. iron deficiency
C. folate deficiency
D. anemia of chronic disease
 Labs to order: reticulocyte count, peripheral smear, haptoglobin,
indirect bilirubin and LDH
Etiologies of extravascular hemolysis include:
Congenital hemoglobin abnormalities: hemoglobinopathies
Erythrocyte membrane abnormalities: hereditary
spherocytosis
Erythrocyte metabolic abnormalities: G6PD deficiency
Auto-immune process: idiopathic, underlying malignancy,
CVD, lymphoproliferative disorders, medications (PCN,
cephalosporins, NSAIDs)
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 X-linked enzyme deficiency that results in decreased glutathione
levels
 Most common form results in severe hemolysis with medications
(sulfa, dapsone) and infection
 Less common Mediterranean form associated with favism
 Dx: enzyme activity testing, may have false negative test in the
setting of acute hemolysis, re-test at 2-3 months
 Etiologies include:
Microangiopathic hemolytic anemia – TTP/HUS, DIC, HELLP
Shearing due to malfunctioning mechanical heart valves
ABO incompatibility
 She has labs consistent with hemolytic anemia, and the following
smear. What do you think is going on and what test can you
send to confirm this?
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 You send a direct antiglobulin test (Coombs test) and it is
positive for IgG. You suspect a diagnosis of warm auto-immune
hemolytic anemia. She is treated with steroids and does well.
 When to transfuse?
General practice: Hct <21% (based on evidence in critically ill pts),
consider at <25% in pt’s with multiple medical problems
Other times to consider: on-going rapid blood loss, highly symptomatic
patients, patient with low Hct and severe cardiovascular disease*
You expect the Hct to increase 3% for each unit of blood transfused
* controversial, area of active research
63 year old female with DM and stage 5 CKD presents
for evaluation of fatigue. Labs reveal Hct 31%, MCV
87, iron 43 (40-155), TIBC 241 (270-535), ferritin 95
(10-180), transferrin sat. 18% (10-45%). How can
you treat her anemia?
A. Transfusion
B. Epo
C. Epo and iron
D. Iron replacement
Burr cells
• Hypoproliferative (low reticulocyte count), normocytic anemia
• For erythropoietin therapy to be effective need adequate iron
stores – ferritin >100/200 and transferrin saturation >20%
• Treatment goal is hemoglobin of 10-11 (Hct 30-33%), higher
levels are associated with increased morbidity and mortality –
carries a Black Box warning
A 27 yr old man of SE Asian descent comes in for a routine exam
required for employment. He is in good health, without weight
loss, fatigue or bleeding sx. FH negative for anemia. Exam is
unremarkable and pt has no HSM. Neg stool guaiac.
Labs: WBC 5.3, HCT 35%, MCV 65, plts 330K, Retic index 0.8.
What is the best test to confirm the most likely cause of this
patient’s anemia?
 A. Obtain CBC on siblings
 B. Perform ultrasound for spleen size
 C. Measure serum ferritin and iron studies
 D. Perform hemoglobin electrophoresis and ferritin
 Thalassemia trait: mild anemia with pronounced microcytosis
(MCV <70), nl RDW
Ethnicity: Mediterranean, Asian, African
Pt are asymptomatic
FamHx is often negative
Alpha-thal trait: dx of exclusion
Beta-thal trait: abnl electrophoresis
 Beta-thalassemia intermedia:
• Ineffective erythropoiesis, more severe anemia, often require frequent
transfusions, at risk to develop of iron overload
Microcytic, hypochromic RBC, target and
teardrop cells
• Most common genetic disease
in persons of African descent,
10% are carriers, 1/600
newborns
• Abnl beta-globin -> Hb S
malforms when deoxygenated -> vasoocclusion
• Normocytic anemia c high
reticulocyte count
• Dx with hemoglobin
electrophoresis
Complications: acute
chest syndrome, AVN,
CVA, cholelithiasis,
infection, pain syndrome
 Evaluation:
Reticulocyte count
Smear – morphologic clues to etiology
CBC – eval. RBC data alongside WBC and Plt counts, RBC indices
Anemia
(not due to acute
blood loss)
Reticulocyte count
High
Low
Smear
Red blood cell
indices, MCV
Microcytic
Normocytic
Macrocytic
 Most common etiologies:
Females – Iron deficiency
Men – Anemia of chronic disease
• Microcytic: iron def., thalassemia
• Normocytic: anemia of chronic disease (25% microcytic), chronic
renal failure, marrow disease, hemolytic anemia*, acute blood
loss*
• Macrocytic anemia: Folate def., B12 def., EtOH
* Not hypoproliferative
• Multiple possible etiologies – iron deficiency, anemia of chronic
disease, renal disease, dilutional
• Anemia is associated with higher mortality rates
• Evaluation is indicated and, in the case of iron deficiency,
treatment may be of benefit
Anker SD, et al. Ferric Carboxymaltose in Patients with
Heart Failure and Iron Deficiency. N Engl J Med
2009;361:2436-48.
Definition: Low oxygen carrying capacity in the blood
due to low erythrocyte mass.
We use the hematocrit or hemoglobin as surrogate
markers for the erythrocyte mass because that it too
difficult to measure.
Hemoglobin of < 12 g/dL in women or a Hemoglobin
of <13 g/dL in men is considered abnormal (WHO
criteria).
The hematocrit is approximately 3 x the hemoglobin.
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 History: Symptoms vary greatly based on the rapidity of the
change in Hct, medical co-morbidities and the cause of the
anemia.
 Physical exam findings: conjunctival rim pallor is the physical
exam finding with the highest positive likelihood ratio (16.7)