Transcript Slide 1

Patient Problems in Anemia
Mary S. Muscato, M.D., FACP
Missouri Cancer Associates
59 y/o woman with RA

59 y/o woman with a 4-year history of RA was
referred for persistent anemia. She has been
treated with NSAIDs, Plaquenil and
methotrexate. She complains of fatigue and
epigastric burning. She denied any change in
bowel habits.
Physical Exam

Mildly weak, VS normal
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Pale conjunctivae
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Several actively inflamed joints
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Stool heme (+)
59 y/o woman with RA
MCV
78
Neut
Bands
Lymph
Mono
Eos
Baso
Plt
528
Other
WBC
4.1
Hb
8.3
Hct
24.6
Morph
77
15
6
2
Aniso,
poik, hypo
59 y/o woman with RA
59 y/o woman with RA
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Retic count 0.7%

WESR 64

CRP 1.05 (elevated)

LDH 140
How Should we Look at this Problem?

Technically, hypochromic, “normocytic”
anemia, but slide shows poik, aniso

MCV a little on the small side: consistent with
iron deficiency and anemia of chronic
disease (ACD)
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Heme(+) stool
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Known RA, CRP elevated
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On methotrexate
More Data
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Ferritin 36
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Fe 6, TIBC 224, Sat 3%
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Upper endo: gastritis
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Soluble Transferrin Receptor (STfR) 6.1
(normal <4.5)
Diagnoses

Iron deficiency (low normal ferritin, but
elevated STfR)
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Anemia of chronic disease
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Gastritis
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Are we done?
Try Not to Make Assumptions!
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Colonoscopy: Large adenocarcinoma in the
ascending colon
59 y/o woman with RA
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The patient underwent a right colectomy and
no other cancer was found. She did not
require adjuvant chemotherapy.

She was treated with four months of oral iron
on an empty stomach. Her repeat Hb rose to
10.4 and the MCV was now 85.

She still has active RA; she was started on
infliximab (Remicade).
59 y/o woman with RA

Infliximab is a monoclonal antibody that
binds to α-TNF (tumor necrosis factor).

Her inflammatory arthritis rapidly improved.
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Over the next 2 months her Hb rose to 13.1,
The MCV rose to 91, her platelets fell to
320,000, WESR and CRP fell to normal.
ANEMIA OF CHRONIC DISEASE
ACD is Cytokine Driven
 Production of pro-inflammatory
cytokines, like TNF and gamma
interferon, damage erythroid progenitors
 Changes in iron homeostasis
 Decreased proliferation of erythroid
progenitor cells
 Decreased production of Epo and
shortened lifespan of RBC’s
Changes in Hb with Remicade
16 y/o girl with rapid-onset anemia
16 y/o girl with rapid-onset anemia
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Moderately pale young woman
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VS T=100.6, pulse 110
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No adenopathy, splenomegaly
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Petechiae on LE’s
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Mildly lethargic
16 y/o girl with rapid-onset anemia
WBC
12.3
Hb
7.1
Hct
22.7
MCV
103
Neut
Bands
Lymph
Mono
Eos
Baso
Plt
14
Other
Morph
79
10
6
3
1
1
3 NRBC
2 metas
Poik,
aniso, 2+
schisto
16 y/o girl with rapid-onset anemia
16 y/o girl with rapid-onset anemia
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Creatinine 1.3
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LDH 2,800
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Retic 18%
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PT, PTT, fibrinogen normal
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Haptoglobin absent
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Bili 2.3, mostly indirect
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U/A 2+ protein
Diagnosis: Thrombotic
Thrombocytopenic Purpura (TTP)
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Treatment begun with emergent daily
plasmapheresis, aspirin, folic acid
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Mental status deteriorated initially, minimal seizure
activity
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LDH & retic gradually dropped, plt count improved,
remained with significant hemolysis
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After two weeks, plasmapheresis switched to every
other day. She eventually recovered and made it to
the prom.
TTP
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TTP is caused by a deficiency of ADAMTS-13,
a metalloprotease which normally cleaves
the large multimers of VWF.
The enzyme deficiency (often acquired)
results in an overabundance of ultralarge
VWF multimers (ULVWF).
These ULVWF bind platelets to endothelium,
leaving platelet-rich microvascular
thrombosis unchecked, leading to microthrombi and intravascular hemolysis.
Alcoholic with Anemia
Alcoholic with Anemia
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42 y.o. man, alcoholic, history of GI bleeds
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Recently drinking, presents with abd pain
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PMH: total gastrectomy 20 years before for
hemorrhagic gastritis
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PE: Anicteric, spiders, liver 14 cm, spleen
down 3 cm
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Stool heme (+)
CBC
WBC
3.4
Hb
9.8
Hct
30
MCV
94
Neut
Bands
Lymph
Mono
Eos
Baso
Plt
71
Other
Morph
67
3
18
10
2
Macro,
aniso,
targets
Alcoholic with Anemia
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Retic 1.6%
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Ferritin 133
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Folate 2.6
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RBC Folate 122 (nl 200-700)
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Creat 1.3
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Bili 1.8
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LDH 1100
Alcoholic with Anemia
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Because of the pancytopenia, confusing
MCV, and concern re mixed anemia, a bone
marrow aspirate and biopsy was done.
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Bone marrow showed
– megaloblastic changes
– absent iron stores
– normal megakaryocytes
Alcoholic with Anemia
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Colonoscopy normal
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B12 level 153 (nl 211-911)
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Causes of anemia:
– History of bleeding: iron loss
– Gastrectomy: loss of IF, loss of iron
absorption, change in mucosa
– Folate lack from not eating broccoli
RX: B12, folate, iron and stop drinking!
57 y.o. Man with Erythrocytosis
57 y.o. Man with Erythrocytosis
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A 57 y.o. man is referred for erythrocytosis.
His history is pertinent for malaise and
pruritis. His wife has noticed that he appears
plethoric. He has smoked 1 ½ ppd for 35
years.

P.E. Plethoric. Decreased breath sounds.
Cardiac exam normal. No hepatosplenomegaly.
CBC
MCV
91
Neut
Bands
Lymph
Mono
Eos
Baso
Plt
450
Other
WBC
13.1
Hb
19.8
Hct
59.5
Morph
78
1
12
4
2
3
Normal
57 y.o. Man with Erythrocytosis
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Retic 2.3%

ABG: pH 7.41, pO2 85, pCO2 38, O2 sat 94%

B12 level 1235
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LAP 112
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Red cell mass: 34 ml/kg, plasma volume
normal
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Erythopoetin: 2 (nl 4-19)
57 y.o. Man with Erythrocytosis
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Diagnosis: Polycythemia Vera
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Confirmatory genetic testing: JAK2, positive
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(Official Symbol: JAK2 and Name: Janus
kinase 2 (a protein tyrosine kinase) Chromosome: 9; Location: 9p24)
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Treatment: phlebotomy to normal hematocrit,
aspirin, possibly hyrdoxyurea
56 y/o with intermittent anemia
56 y/o with intermittent anemia
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A 56 y/o woman presents with a mild anemia. History
reveals that she was once told by a doctor that she
might have had some jaundice. Generally healthy, no
infections.

FH + for her 86 y/o mother diagnosed last year with
massive splenomegaly and Hb 6. Thought to be
MDS, but she clinically improved.

PE normal except spleen tip palpable.
CBC
Hb
10.7
Hct
33.1
MCV
104
Neut
Bands
Lymph
Mono
Eos
Baso
Plt
152
Other
WBC
4.6
Morph
67
18
10
3
2
Macro,
polychromasia
Peripheral Smear

Some polychromasia seen. Hematologist
noted normocytic spherocytes. No
poikilocytosis.
56 y/o with intermittent anemia
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Retic count 11.2%
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MCHC elevated
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Bili 2.2, 1.8 Indirect
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LDH 317
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Haptoglobin normal
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Nuclear Medicine liver-spleen scan shows
only minimal splenomegaly

Direct Coombs negative
56 y/o with intermittent anemia
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Osmotic fragility ordered. Returns showing
increased osmotic fragility, consistent with
hereditary spherocytosis.
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The patient’s mother had come with her; she was reexamined. Spleen now only 6 cm and Hb back up to
11.0! Peripheral smear: spherocytes.
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Her son was also in the exam room. His smear also
showed spherocytes.
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(This is a true story!)
29 y.o. G3P2 woman with anemia
29 y.o. G3P2 woman with anemia
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29 y.o. African-American woman is referred
during the 5th month of her 3rd pregnancy.
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Pregnancy has been uncomplicated, as have
her previous pregnancies.

She has been faithfully taking her prenatal
vitamins.

P.E. normal; uterine size 22 weeks.
CBC
WBC
6.5
Hb
8.8
Hct
24
MCV
78
Neut
Bands
Lymph
Mono
Eos
Baso
Plt
340
Other
Morph
65
24
9
2
Micro,
targets
29 y.o. G3P2 woman with anemia

Retic 2.1%

Ferritin 140

Fe/TIBC 110/290

STfR 2.9 (normal)
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Hb electrophoresis normal: A2 and F not
elevated

Cord blood at time of delivery showed Hb
Bart’s (tetramers of γ-chains)
Globin Chain Dimers
A1
A2
F
α



β

γ
δ


Summary: Anemia for M3s

Always pay attention to:
– History, PE: do they fit?
– Peripheral smear
– Retic
– MCV
– LDH, bili
– Blood in stool or urine