Transcript Clinical Approaches to Anemia Presented by: Cheryl Morrow MD

Clinical Approaches to
Anemia
Presented by: Cheryl Morrow MD
I would like to acknowlege and thank the
American Society of Hematology
for granting permission
to use their educational slides to illustrate this lecture.
You will be able to access all of the images
that I will be using by going directly to the
ASH Image Bank @
http://imagebank.hematology.org/
And type in the Slide number.
Happy Birthday,
Ernest!
Anemia: Course Objectives
At the end of the program, the participant will be able to:
 Name the common physiological responses and symptoms that
occur in anemia
 Name the laboratory tests that should be ordered to determine the
degree of severity and type (etiology) of anemia with which a
given patient is presenting.
 List the likely cause(s) of anemia when provided the results of the
patient’s laboratory tests for anemia
 Based on an understanding of anemia etiology, name one
recommended treatment option for each of the following anemia
types: nutritional deficiency, CKD, blood loss anemia,
autoimmune anemia, anemia due to bone marrow failure.
Anemia – So why do we care ?
• Oxygen: the most essential element of human life - critical for:
• Cellular respiration, growth and repair
• Vital organ function: brain, heart, lung, kidneys, liver, nervous
• Quality of life: movement, communication, senses, perceptions
• Oxygen is critical but dumb !
(I’m a dumb ox) - it doesn’t
know where it needs to go, how to get there, nor how many of the
crew are needed to get the job done at each location.
• Hemoglobin has the esteemed jobs of both escorting and
managing the entire crew of available oxygen molecules
Hemoglobin the Super Hero:
The Proper Functioning of Hemoglobin requires:
• adequate numbers (inadequate = anemia)
• healthy molecules (Sickly = Hb S, C, thalassemia)
• in a healthy environment (Sick = oxygen; CO )
Oxygen-Hemoglobin Dissociation Curve
100% ___________________________________________________________
65
35% oxygen dropped off
50
50% oxygen dropped off
% Sat.
35
65% oxygen dropped off
0%___
50
0
PaO2 mmHg
100
• Functional definition of anemia:
inadequacy of one’s hemoglobin, or the red blood cells
that contain the hemoglobin, to transport and deliver
adequate oxygen supplies to the tissues where it is
needed.
• Technical definition of anemia:
• Males: hemoglobin < 14 g/dl; hematocrit < 40 %
• Females: hemoglobin < 12 g/dl; hematocrit < 37%
Sx’s of Anemia = Sx’s of Hypoxemia
o
o
o
o
o
o
o
o
o
o
o
Tired, Sleeping more
Loss of energy, weakness
Pale skin
Easy Fatigue
Tachycardia, esp. with exertion
New onset AF
Shortness of breath
Dizziness
Headache
Confusion, poor concentration
Angina
Go to ASH Website and select slide 3632
The RBC indices tell us about the Red Cell Physical
Characteristics, and hemoglobin content:
Index
Full
Name
What’s
Normal
Think
measured Range
MCV
Mean
Corpuscular
Volume
Average
Red blood cell
Size
80-100
Femtoliters
MCH
Mean
Corpuscular
Hemoglobin
Average
amount of Hb
in each RBC
27-31
Picograms/
cell
MCHC
Mean Corpuscular
Hemoglobin
Concentration
Hb density:
Is it compacted
or spread out?
32-36
Grams/
deciliter
RDW
Red Blood Cell
Distribution
Width
Variations in
RBC size
11.5-14.5 %
So let’s talk about anemia:
• Anemia develops when there is an imbalance between
the production and the loss/destructrion of RBC’s.
• Anemia can also be caused by a genetic defect causing
the production of faulty hemoglobin and/or RBC’s.
• Thus, the causes of anemia can be classified as either …
Low make,
High take,
Mistake !
Low Make
High Take
Mistake
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
Microcytic Anemias . . . .
“Anorexics love to ingest small”
( MCV< 70)
Case 1:
Mrs. B is a 92 year old nursing home patient who, on routine lab
testing, was found to have a hemoglobin of 9.0, and a hematocrit
of 28.1. The patient’s aids note that she requires more assistance
with ADL’s of late. She is weaker and seems more confused.
Other Labs: WBC 6.9 (5-10)
platelet 460 (150,000-400,000)
MCV 70.5 (80-100)
MCH of 22.5 (27.0-32.0)
MCHC 32.0 (32-36)
RDW was elevated at 17.8 (11.5-14.5)
What is in the differential diagnosis? What do we do next?
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin (& Iron Studies)
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
SideroBilirubin
Liver
blastic
Haptoglobin ETOH Enzymes
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
Case 1 continued:
Iron studies:
Ferritin: 8 (10-250) 
LOW
Serum Iron: 14 (35-150)  LOW
TIBC: 254 (250-450) 
NORMAL
% Saturation: 6 (12-50)  LOW
Causes of Microcytic Anemia:
Condition
Causes
CBC/other
Iron studies
Iron
Deficiency
Bleeding,
pregnancy
Platelets up;
RDW up
Serum Fe , % Suppl. Iron
Sat. ,Ferritin Stop bleed
TIBC
Anemia of
Chronic
Disease
Diseases
with chronic
inflammation
Elevated ESR Serum Fe , % Treat
& CRP; MCV Sat. Ferritin
Underlying
is normal-low TIBC
disease
Beta
Thalassemia
Trait
hereditary
Increased
HbA2, HbF -
Sideroblastic
Anemia
Hereditary &
ETOH, B6 def.
Isoniazide,
Zyvox, MDS
Prussian Blue
Stain of BM
shows ringed
sideroblasts
Lead
Toxicity
Lead ingestion Basophilic
Often from
stipling
paint chips.
Serum Fe, %
Sat.,Ferritin
electrophoresis TIBC normal
Treatment
Usually none
Mis-dx’d
As Fe-defic.
Serum Fe , % D/C causative
Sat. Ferritin
agent; treat
TIBC nl
with Vit. B6 helps 40-80%
Serum Fe , % D/C lead
Sat. ,Ferritin Exposure;
TIBC
Chelation
Therapy prn
Case 1 continued:
Iron studies:
Ferritin: 8 (10-250) 
LOW
Serum Iron: 14 (35-150)  LOW
TIBC: 254 (250-450) 
NORMAL
% Saturation: 6 (12-50)  LOW
Diagnosis: Iron Deficiency Anemia
Treatment: Supplemental iron; Look for occult GI bleed
• Go to ASH website and select slide 4045
Case 2.
Peter is a six year old boy who developed headaches,
difficulty sleeping, stomach pain, weight loss, irritability
and regression in school over the past several months.
His mother, who is a single mom, usually works until 6 at
night and the patient and his ten year old sibling are left
alone in their apartment in the late afternoon until Mom
returns.
Labs: His Hb is 8,8; Hct is 26.2; His Ferritin was WNL.
His other iron studies were within normal limitis.
His peripheral blood film as follows:
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin (& Iron Studies)
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
SideroBilirubin
Liver
blastic
Haptoglobin ETOH Enzymes
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
Causes of Microcytic Anemia:
Condition
Causes
CBC/other
Iron studies
Iron
Deficiency
Bleeding,
pregnancy
Platelets up;
RDW up
Serum Fe , % Suppl. Iron
Sat. ,Ferritin Stop bleed
TIBC
Anemia of
Chronic
Disease
Diseases
with chronic
inflammation
Elevated ESR Serum Fe , % Treat
& CRP; MCV Sat. Ferritin
Underlying
is normal-low TIBC
disease
Beta
Thalassemia
Trait
hereditary
Increased
HbA2, HbF -
Sideroblastic
Anemia
Hereditary &
ETOH, B6 def.
Isoniazide,
Zyvox, MDS
Prussian Blue
Stain of BM
shows ringed
sideroblasts
Lead
Toxicity
Lead ingestion Basophilic
Often from
stipling
paint chips.
Serum Fe, %
Sat.,Ferritin
electrophoresis TIBC normal
Treatment
Usually none
Mis-dx’d
As Fe-defic.
Serum Fe , % D/C causative
Sat. Ferritin
agent; treat
TIBC nl
with Vit. B6 helps 40-80%
Serum Fe , % D/C lead
Sat. ,Ferritin Exposure;
TIBC
Chelation
Therapy prn
• Go to ASH website and select slide 3452
Diagnosis:
• The blue speckles seen on several RBC’s is Basophilic Stippling.
• Basophilic stippling is seen in heavy metal poisoning,
particularly lead poisoning, the thalassemias; and a few other
conditions.
• His blood lead level was 22 mg/dl (upper nl is 5 mg/dl for child)
• Diagnosis was made: chronic lead poisoning caused by ingestion
of paint chip fragments.
• Treatment: hospitalized for IV chelation therapy with DMSA and
returned to his baseline.
Lead Poisoning
Case 3
HPI: A 42-year-old woman was referred for mild, chronic
microcytic anemia discovered 18 years before. She c/o chronic
fatigue that she has learned to live with.
PE: was normal except for some generalized weakness.
Labs: Hb 9.6 g/dL, MCV 73 fL, MHC 23 pg (27-32) RDW
27% (10.5-14.5). The WBC and platelet counts were WNL.
Iron studies: ferritin 465 (10-252). Fe, % Sat are
Her peripheral smear follows:
TIBC nl.
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin (& Iron Studies)
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
SideroBilirubin
Liver
blastic
Haptoglobin ETOH Enzymes
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
Causes of Microcytic Anemia:
Condition
Causes
CBC/other
Iron studies
Iron
Deficiency
Bleeding,
pregnancy
Platelets up;
RDW up
Serum Fe , % Suppl. Iron
Sat. ,Ferritin Stop bleed
TIBC
Anemia of
Chronic
Disease
Diseases
with chronic
inflammation
Elevated ESR Serum Fe , % Treat
& CRP; MCV Sat. Ferritin
Underlying
is normal-low TIBC
disease
Beta
Thalassemia
Trait
hereditary
Increased
HbA2, HbF -
Sideroblastic
Anemia
Hereditary &
ETOH, B6 def.
Isoniazide,
Zyvox, MDS
Prussian Blue
Stain of BM
shows ringed
sideroblasts
Lead
Toxicity
Lead ingestion Basophilic
Often from
stipling
paint chips.
Serum Fe, %
Sat.,Ferritin
electrophoresis TIBC normal
Treatment
Usually none
Mis-dx’d
As Fe-defic.
Serum Fe , % D/C causative
Sat. Ferritin
agent; treat
TIBC nl
with Vit. B6 helps 40-80%
Serum Fe , % D/C lead
Sat. ,Ferritin Exposure;
TIBC
Chelation
Therapy prn
• Go to ASH website and select slide 24956
• Peripheral Smear showed a double population of
RBC’s: one normal and one extremely microcytic and
hypochromic. Very unusual  need a bone marrow.
• Bone marrow aspirate: 35% of erythroid cells were
ringed sideroblasts: nucleated erythroblasts with
granules of (Prussian-blue stained) iron in perinuclear
mitochondria
• In sideroblastic anemia, the body/RBC has iron
available but cannot incorporate it into hemoglobin.
Ringed sideroblasts = Sideroblastic Anemia
• Go to ASH website and select slide 1157
Case 3:
• X-linked sideroblastic anemia was confirmed by DNA
sequencing on this patient. A skewed X-chromosome
inactivation ratio explained the phenotype with two cell
populations. Gender preval.: 1/3 women and 2/3 men.
• Aquired Sideroblastic anemia: myelodysplastic syndrome,
ETOH abuse, lead poisoning, B6 defic., drugs (Isoniazid,
linezolid, etc)
• Treatment: Oral pyridoxine (B6) therapy for all types
with varying effectiveness. In this real case, pyridoxine
increased her Hb to 11.4; and peripheral films showed
disappearance of the microcytic population.
Diagnosis: X-Linked Sideroblastic Anemia
Normocyctic Anemias . . . .
“average men hunt burgers”
(MCV 80-100)
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
• Reticulocytosis:
 Reticulocytes: immature RBC’s pushed out of the bone
marrow early because of anemia. They stain “blue” because
of nuclear fragments. These fragments show up better on a
vital stain which enables counting of reticulocytes
 Polychromasia: the bluish tint of the reticulocytes on a
routine Wright’s stain, provides evidence of immature
RBC’s
• Example: Hemolytic disease of the newborn secondary to
ABO incompatibility
• Notice the polychromasia (causing an increase in MCV)
• Notice the nucleated RBC
• Go to ASH website and select slide 3513
Case 4
A 58 year old, obese, diabetic female presents with c/o
feeling exhausted. She states that over the past 1 month,
she has gotten increasingly short of breath while walking
from the parking lot to his office. Over the past one week,
she has also experienced the sensation of her “heart
pounding out of her chest” when walking back and forth to
his car.
When you ask her about pain, she admits to chronic back
and joint pain for which she regularly takes ibuprofen with
good relief. She denies dyspepsia, diarrhea, melena and
hematochezia. She is post-menopausal. Her PE is normal.
What is the Ddx ?
Case 4 continued:
Relevant lab work is as follows:
WBC 7.6
MCV 92
Hb 8.2
MCH 29 (27-32)
Hct: 24.5
Serum Fe normal
Plt: 333
Ferritin normal
Diff: normal
RBC morphology on next page.
Reticulocyte count: 0.4 (0.5-2.5)
Na 135
K+ 4.4
Cl 106
CO2 24
BUN 64
Creat. 3.2
GFR: 19
What kind of anemia does she have?
• Go to ASH website and select slide 3632
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
• Case 4
• Answer: she has Anemia of Chronic Kidney
Disease with acute on chronic renal failure
secondary to NSAID use.
• Treatment: Stop NSAIDS! Treat anemia with
erythropoetin. Monitor kidneys closely
Case 5
HPI: A 21-year-old African-American woman presented for
routine prenatal care for her second pregnancy. Her past
medical history included normocytic anemia of uncertain
etiology, for which she was treated with iron, during her first
pregnancy. Her physical examination was unremarkable.
Labs: hemoglobin, 9.4 g/dL; MCV 81 fl; RDW 15.3
WBC and platelet counts were WNL
Electrophoresis/chromatography for.
hemoglobinopathy were normal,
Here is her periperal blood film:.
• Go to ASH website and select slide 17970
Hemolytic Anemia
 Peripheral blood smear showed many elliptocytes, which
is diagnostic of hereditary elliptocytosis (HE).
 HE is caused by various gene mutations ultimately
affecting the red cell cytoskeleton and membrane protein
integrity  Spontaneous hemolysis not mediated by Ab’s.
 HE is seen in numerous ethnic groups; with incidence
highest in west and central Africans.
 Most patients with heterozygous HE are asymptomatic,
although some may demonstrate hemolytic anemia and
splenomegaly.
 Other lab findings: haptoglobin, LDH, Indir. Bilirubin,
direct antiglobulin test (DAT) is neg. b/c not Ab-mediated.
 Treatment: Folic acid reduces hemolysis.
Case 6.
HPI: A previously healthy 23 year old male
college student was noted by his buddies to
be pale, fatigued, and just not keeping up.
His mother comes to visit and notes that
he has lost 10 pounds over the past 1 month.
She
She wonders if he has been using drugs.
She brings him to your office for evaluation.
Lab tests reveal: WBC 11.8, Hb 8.3, Hct 26.0, MCV 96
What’s your Ddx? What questions do we need to ask him?
Case 6, continued:
Upon your ROS, he reveals that he has had
Multiple episodes of loose stool over the
Past two months. When pressed, he admits
That the stools have been maroon in color.
Additional Labs:
Na 148, K 3.2, CO2 16, BUN 32, Creat. 1.2
(BUN/Creat. Ratio 27).
WBC 11.8, Hb 8.3, Hct 26.0, MCV 96
What’s your Ddx? What do we do next to confirm the dx?
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
Case 6, continued:
Upon your ROS, he reveals that he has had
Multiple episodes of loose stool over the
past 2-3 weeks. When pressed, he admits
That the stools have been loose and bloody.
Additional Labs:
Na 148, K 3.2, CO2 16, BUN 32, Creat. 1.2
(BUN/Creat. Ratio 27).
WBC 11.8, Hb 8.3, Hct 26.0, MCV 96
His peripheral blood film is the next slide.
What’s your Ddx? What do we do next to confirm the dx?
• Go to ASH website and select slide 3666
Case 6, continued:
 The blood film confirms what the indices
have told us: normocytic, normochromic
 We order a reticulocyte count and it comes
back at 2.5% (normal is 0.5- 2.5 %). The
Bleed is still too acute for a great response.
Diagnosis:
You refer him to GI who scopes him and diagnoses him with
new onset Crohns. He starts anti-inflammatory Meds and
his symptoms subside. He has a normal bone marrow so,
when given adequate iron, and nutrients, he will replace his
lost RBC’s without difficulty.
Macrocytic Anemias . . . .
“Large men routinely hunt virtually ALL food”
MCV > 100
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
• Reticulocytosis:
 Reticulocytes: are immature RBC’s pushed out of the bone
marrow early because of anemia. They are larger than
mature RBC’s and thus increase the MCV.
 Polychromasia: the bluish tint of the reticulocytes on a
routine Wright’s stain, They stain “blue” because of
retained nuclear fragments. These fragments show up better
on a vital stain which enables counting of reticulocytes
 : provides evidence of immature RBC’s
• Example: Hemolytic disease of the newborn secondary to
ABO incompatibility
• Notice the polychromasia (causing an increase in MCV)
• Notice the nucleated RBC
• Go to the ASH website and select slide number 3513
• Megaloblastic Anemia and Hypersegmented PMN’s
• Megaloblastic Anemia; a macrocytic anemia that
results from inhibition of DNA snthesis during RBC
production.
• A mismatch occurs in the maturation of nucleus and
cytoplasm as the result of the lack of folic acid or B12.
• As a result, RBC’s have lacier nuclei and larger cell size;
Neutrophils become Hypersegmented,- 6 or more lobes
Peripheral films will also have giant bands
• Go to the ASH website and select slide 2869
Megaloblastic Anemia, continued:
• BM aspirate from a patient with folic acid deficiency is shown
• erythroid hyperplasia with marked nuclear/cytoplasmic
dysynchrony noted at all stages of erythroid maturation; and
nuclear budding.
• The Megaloblastic Anemias include:
• B12 deficiency from dietary lack
• B12 deficiency due to malabsorption (lack of Intrinsic Factor)
known as Pernicious Anemia. Do Schilling Test to differentiate.
• Folic Acid defiency – (Pregnant women at increased risk)
• To differentiate, check B12, Folic Acid and MMA levels.
• With B12 deficiency, will also have neurologic symptoms.
• Go to the ASH website and select slide 4117
• Pernicious Anemia
• Note the macro-ovalocytes characteristic of vitamin B12
or folate deficiency states.
• Go to the ASH website and select slide 1544
• Go to the ASH website and select slide 2869
Case Study 7.
• A 21-year-old woman presented with severe anemia and
mild splenomegaly.
• Her CBC revealed a Hb of 6.8 g/dL, hematocrit 22%,
MCV 114 fL, and MCH 21.4 (27.0-32.0).
• The reticulocyte count was 3.6%.
• Her peripheral film is as follows:
• Go to the ASH website and select slide 14465
Case Study 7.
• The peripheral smear (panel A) showed macrocytic target
cells, polychromatophilia, macro-ovalocytes, and a few
microcytes.
• In view of the target cells, liquid chromatography was
performed. Hemoglobin E disease was Dx’d. It typically
shows microcytic hypochromic anemia with target cells.
• Her serum B12 level was 94 ng/L (normal range, 180-640
ng/L) with normal serum and red cell folate levels.
• A diagnosis of vitamin B12 deficiency with hemoglobin
E disease was made. After 2 weeks of supplementation of
vitamin B12 and folate, her hemoglobin rose to 9.6 .
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
• Macrocytic Anemias (Non-megaloblastic)
• Also occur with various organ diseases such as
Hypothyroid, liver disease, and in alcoholism.
• In addition to the expected abnormal lab
studies associated with each of these
conditions:
O
Target cells are particularly associated with
Liver Disease.
• For the remainder of this lecture, we’ll take a quick look
at some blood films and clinical characteristics of other
anemias that we do not have time to present in Case
Study format.
• The first is Sickle cell disease – Note the RBC
morphology on the following slides that results in the
deformed cells plugging up blood vessels and causing
painful ischemic attacks.
• In addition to the RBC findings of sickled cells, this
image shows a nucleated RBC (arrow). Because of the
marked anemia, the bone marrow pushes out immature
cells.
• Go to the ASH website and select slide 3959
• For the remainder of this lecture, we’ll take a a quick look
at miscellaneous blood films of other anemias that we do
not have time to go into today.
• The first is Sickle cell disease – Note the RBC
morphology
• In addition to the RBC findings of sickled cells, this
image shows a nucleated RBC (arrow).
• Pappenheimer bodies may be found in a variety of
conditions including megaloblastic anemia, thalassemias,
hemolytic anemias, and post-splenectomy.
• Go to the ASH website and select slide 3887
Hemoglobin C Disease
• Hemoglobin C crystals crystalize outside of and inside of
RBC’s causing disruption of cells and blockage of
vessels..
• Both extracellular (single arrows) and intracellular
crystals are noted.
• Go to the ASH website and select slide 3787
RBC morphology in thalassemia
• A hypochromic polychromatophilic RBC (arrow) is
shown .
• The smear from a child with hemoglobin of 7.5 g/dl,
RBC of 5.9 × 106/ul and an MCV of 47 fL consistent
with a diagnosis of thalassemia.
• The marked RBC microcytosis and hypochromia are
evident.
• The child had received an RBC transfusion prior to smear
being performed accounting for the dual population of
RBCs.
• A spherocyte (arrow) is present on the smear and is of
donor origin
• Go to the ASH website and select slide 3955
• RBC abnormalities in S/β thalassemia
• Peripheral smear from a patient with S/β &plus;
Thalassemia is shown. The MCV in this patient was 67
femtoliters consistent with microcytosis.
• Hemoglobin analysis showed 67% hemoglobin S; 25%
hemoglobin A; 2% hemoglobin F; and 6% hemoglobin
A2. Sickle cell (small arrow) and target cell (large arrow)
typical of this disorder are shown.
• Go to the ASH website and select slide 4026
• Microangiopathic hemolytic anemia secondary to
artifical aortic valve malfunction
• The smear is shown at higher magnification and
demonstrates more clearly the marked schistocytosis.
• Go to the ASH website and select slide 1067
MCV - Based Approach to Anemia Diagnosis :
MCV
<80
Microcytic
80 – 100
Normocytic
Ferritin & Iron Studies
Reticulocyte Count
Low
Normal
Iron Thalassemia
Defic. HemoglobinAnem. opathy
Hemoglobin
Electrophoresis
Lead poisoning
High
Low
Normal
> 100
Macrocytic
High
Anemia
Chronic
Disease
Blood Smear Morphology
-- HS PMN’s*
Anemia Acute Hemolysis Polychro- Target
Chronic Blood Chronic
masia
Cells
Disease Loss Bld.Loss Reticulo- Liver
CRP,
cytosis
Disease
ESR
LDH
BMP
SideroBilirubin
Liver
E-po.
blastic
Haptoglobin ETOH Enzymes
Defic
anemia
Direct AntiAbuse
globulin test Hypothyroid
Lead
Bone Marrow
Bone Marrow
Level Ringed Ringed
sideroblasts
Melodysplasia
TFT’s
Sideroblasts
* HS PMN’s = Hypersegmented Polymorphonuclear Neutrophils
+ HS PMN’s
Vit B12
Deficiency
Folate
Deficiency
B12,
Folate
Levels,
MMA,
Schilling
Test
Microcytic Anemias . . . .
“Anorexics love to ingest small”
( MCV< 70)
Normocyctic Anemias . . . .
“average men hunt burgers”
(MCV 80-100)
Macrocytic Anemias . . . .
“Large men routinely hunt virtually ALL food”
MCV > 100
THE END …
and Ernest, it’s
finally time for your
birthday vacation !!!