Chapter 4

Anemia:
Diagnosis and Clinical
Considerations
1
1. Study Questions
2. Homework
Assignment
3. Exam for Unit III
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Anemia: Diagnosis and Clinical
Considerations
InChapter 4, you will learn how
anemia is diagnosed using different
classification systems. You will also
see how anemia affects an individual's
physiology and how the body tries to
compensate for the anemia.
Laboratory tests used to diagnose
anemia are discussed. Finally, you
will learn the normal ranges for each
parameter of a CBC and how to
calculate the red blood cell indices. 3
 Definition of Anemia 1 of 2

Inabilityof blood to supply tissues with

adequate oxygen for proper metabolic
function.
Diagnosis made by patient history, physical
examination, signs and symptoms, and
hematological laboratory findings.
Usually associated with decreased levels of
hemoglobin or hematocrit (packed red cell
volume) - Abnormal hemoglobin may give
appearance of anemia (methemoglobin).
Usually associated with decreased RBCs.
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 Definition of Anemia 2 of 2

Classified as moderate (Hb 7-10 g/dl) or

severe (Hb <7g/dl).
Physical signs include difficulty breathing
(dyspnea), vertigo, light-headedness,
muscle weakness, headaches, and lethargy.
Rapidly developing anemia may be
associated with hypotension and
tachycardia.
Two general forms of anemia: Absolute
Anemia (decrease in red cell mass) and
Relative Anemia (increased plasma volume
gives appearance of anemia). 5
Considerations by Age, Sex, and
Other Factors 1 of 2

Newborns less than one week old have

hemoglobin of 14-22 g/dl.
By six months of age, hemoglobin runs
between 11 and 14 g/dl.
Between 1 year and 15 years of age
hemoglobin runs between 11-15 g/dl.
Normal adult hemoglobin depends on
gender:
12-16 g/dl
14-18 g/dl
In geriatric age group, men and women
have same hemoglobin range: 12-16 g/dl.6
Considerations by Age, Sex, and
Other Factors 1 of 2

Normal ranges do depend on patient

populations.
Other factors influencing normal
hemoglobin include:
Environment: elevation of Denver vs. New
Orleans
Physical Health:e.g. lung or kidney disease
Nutritional deficiencies
Blood loss
Bone marrow replacement
Chemicals / Radiation
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 Causes of Anemia

Nutritionaldeficiencies
Hemolytic disorders
Blood loss
Bone marrow (hypoproliferative)
Infection
Toxicity
Hemopoetic stem cell damage
(maturation disorder)
Heredity or acquired defect
Unknown
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 RBC and Hemoglobin
Production 1 of 2
In healthy individuals, about 1% of RBCs lost
daily. Bone marrow continuously produces
RBCs to equal daily loss. Reticulocyte count
is a lab measurement of this loss. Normal
retic count is 0.5-2.0% of circulating RBCs.
Replacement requires functioning bone
marrow, normal RBC maturation and ability
to release mature RBCs to peripheral blood.
Proper nutrition required (B12, Folate). Also
requires normal hemoglobin synthesis.
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 RBC and Hemoglobin
Production 2 of 2
Severe anemia (<7 Hb) may see other organ
system failures: Cardiac and respiratory.
Do have compensatory mechanism: See an
increase in 2,3-DPG levels which results in
an increase in RBCs oxygen carrying
capacity.
Erythropoietin levels (Epo) useful diagnostic
tool. Anemic people usually respond by
increasing erythropoietin levels.
Erythropoietin is a hormone produced in the
kidney. Levels of erythropoietin varies with
oxygen tension in kidney tissues ( Oxygen
- Epo, and vice versa) 10
 Clinical Diagnosis

Made by combination of factors including:

patient history, physical signs and changes
in hematologic profile (CBC).
Signs and symptoms usually non-specific:
fatigue, weakness, gastrointestinal
symptoms (nausea, constipation and
diarrhea), shortness of breath - especially
after exertion.
Physical signs of anemia are usually not
specific for the cause.
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Physiological Response
oxygen carrying capacity
Shift to right
2,3-DPG
Cardiac output
Circulation shifts to critical
areas
RBC production
Erythropoietin
Left shift on blood smear
Reticulocyte count 12
 Classification of Anemias

Have a variety of ways - depending

on criteria used:
Functional
Morphological
Clinical
Quantitative

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 Functional
Classification of Anemias

Decreased RBC production

(hypoproliferative)
Defective hemoglobin synthesis
Fe deficiency
B12 deficiency
Folate deficiency
Impaired bone marrow or stem cell function, as
in leukemia
Increased RBC destruction, as in sickle cell
anemia or hemolytic anemia
Combination of the two (sometimes called
ineffective erythropoiesis) 14
 Morphological
Classification of Anemias

Morphological based on sizes and

color of RBCs
Normochromic Normocytic
Hypochromic Microcytic
Normochromic Microcytic
Normochromic Macrocytic

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 Clinical
Classification of Anemias

According to their associated causes:

Blood loss
Iron deficiency
Hemolysis
Infection
Nutritional deficiency
Metastatic bone marrow replacement

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 Quantitative
Classification of Anemias

Quantitatively by:
Hematocrit
Hemoglobin
Blood cell indices
Reticulocyte count

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Hemoglobin and Hematocrit
1 of 2

Anemia usually diagnosed on either

hemoglobin or hematocrit values.
Remember, normal ranges vary depending
on age, gender, state of hydration, patient
positioning and local patient population.
Hemoglobin analysis based on
spectrophotometric absorbance readings of
cyanmethemoglobin.
Hematocrit is packed cell volume (PCV)
determined by centrifugation:
Normal range for adult men is 42-52%
Normal range for women is 37-47% 18
Hemoglobin and Hematocrit
2 of 2

On basis of H&H, anemia can be classified as mild,

moderate, or severe.
On basis of duration of onset, anemia can be
classified as either chronic or acute.
Rules of Three:
RBC X 3 = Hemoglobin
Hemoglobin X 3 = Hematocrit
Ratio of Hb and Hct will vary with cause of anemia
and affect the RBC indices, particularly the MCV
(Mean Corpuscular Volume).
Microscopic examination of peripheral blood smear
is required for evaluation of anemia. Bone marrow
aspirates and smear evaluation may also be
needed. 19
 RBC Indices

RBC indices include:

Mean Corpuscular Volume (MCV)
Mean Corpuscular Hemoglobin (MCH)
Mean Corpuscular Hemoglobin
Concentration (MCHC)
RBC Distribution Width (RDW)

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 MCV
Mean cell volume
MCV is average size of RBC
MCV = Hct x 10
RBC (millions)
If 80-100 fL, normal range, RBCs considered
normocytic
If < 80 fL are microcytic
If > 100 fL are macrocytic
Not reliable when have marked anisocytosis

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 MCH

MCH is average weight of

hemoglobin per RBC.
MCH = Hgb x 10
RBC (millions)

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 MCHC
MCHC is average hemoglobin
concentration per RBC
MCHC = Hgb x 100
Hct (%)
If MCHC is normal, cell described as
normochromic
If MCHC is less than normal, cell
described as hypochromic
There are no hyperchromic RBCs

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 RDW

Most automated instruments now

provide an RBC Distribution Width
(RDW)
An index of RBC size variation
May be used to quantitate the amount
of anisocytosis on peripheral blood
smear
Normal range is 11.5% to 14.5% for
both men and women 24
 RBC Indices and Other Tests
RBC indices are automatically calculated by
instruments.
Microscopic evaluation will determine if
RBCs are normocytic, microcytic, or
macrocytic and normochromic or
hypochromic.
Use of RBC indices in differential diagnosis
can provide picture of what is occurring
clinically.
If anemia caused be bone marrow failure,
requires information about RBC production.
Information obtained from reticulocyte
count. Reticulocyte count measures 25
 Normals

COMPONEN NORMAL RANGES

T
WBC 4.8-10.8 x 103/L
RBC Male 4.7-6.1 x 106/L; Female 4.2-5.4 x
106/L
Hgb Male 14-18 g/dL; Female 12-16 g/dL
Hct Male 42-52%; Female 37-47%
MCV 80-100 fL
MCH 27-31 pg
MCHC 32-36%
RDW 11.5-14.5%
Plt 150,000-350,000/L
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Retic 0.5-2.0%
 Treatment of Anemias

Treated according to cause; Should

know cause before beginning
treatment.
Patient can have more than onecause
of anemia.
Must use diagnostic tests to determine
cause(s).
Do diagnostic tests before
transfusions, because transfusions
obscure and confuse findings. 27
 Hgb
(In the Diagnosis of Anemia)

Hbg is the main component of RBCs

and carries oxygen to tissues.
Three methods to measure
hemoglobin:
Cyanmethemoglobin (recommended
method)
Oxyhemoglobin
Iron Content
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 Cyanmethemoglobin
(method to measure Hgb) 1 of 2

1. Blood is diluted in a solution of

potassium ferricyanide and
potassium cyanide, which oxidizes
the hemoglobin to form
methemoglobin.
2. Then methemoglobin forms
cyanmethemoglobin in the presence
of the potassium cyanide.
3. Absorbance of solution is read in
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 Cyanmethemoglobin
(method to measure Hgb) 2 of 2

Advantages:
Most forms of hemoglobin are measured
Sample can be directly compared with a
standard
Solutions are stable
Method is precise
Errors in the measurement of Hgb:
Must draw and handle specimen correctly
Reagents must be properly prepared and
stored
Equipment failure 30
 Hct
(In the Diagnosis of Anemia) 1 of 3

Is packed RBC volume

Is ratio of RBC volume to volume of whole
blood
Usually expressed in percentage (42%) or
as decimal fraction (.42)
Venous and arterial hematocrits closely
agree
Specimen of choice is EDTA
(ethylenediaminetetra acetic acid),
oxalate or heparin 31
 Hct
(In the Diagnosis of Anemia) 2 of 3

Measurement done by centrifugation

or through calculations performed on
many automated measurements.
Calculated hematocrit is product of
MCV and RBC count.
Normal ranges are 42-52% in men and
37-47% in women.
Normal ranges also vary among age
groups, institutions, and geographic
locations. 32
 Hct
(In the Diagnosis of Anemia) 3 of 3

Problems
in measurement of
hematocrits include:
Incorrect centrifuge calibration
Choice of sample site
Incorrect ratio of anticoagulant to blood;
Improper amount of blood drawn
Reading errors

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 RBC Indices
(In the Diagnosis of Anemia) 1
of 2

RBC indices are readily available from

the automated hematology counting
devices
MCV is measured directly or
calculated from hematocrit and RBC
count; MCH and MCHC are both
calculated
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 RBC Indices
(In the Diagnosis of Anemia) 2 of 2

In various anemic states, indices may

be altered:
Microcytic Anemia:
MCV usually 50-80 fL
MCH usually 15-25 pg
MCHC usually 22-30%
Macrocytic Anemia:
MCV usually 100-120 fL

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 Peripheral Blood Smear
(In the Diagnosis of Anemia)
Very useful in diagnosing and
classifying anemias
Look for:
Neutropenia
Thrombocytopenia
Hypochromia
Size and shape of RBCs
Unusual leukocytes (hypersegmentation)
Red cell inclusions: basophilic stippling,
Howell-Jolly bodies
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 Reticulocyte Count
(In the Diagnosis of Anemia)

Useful in determining response and

potential of bone marrow.
Reticulocytes are non-nucleated RBCs that
still contain RNA.
Visualized by staining with supravital dyes,
including new methylene blue or brilliant
cresyl blue; RNA is precipitated as dye-
protein complex.
Normal range is 0.5-2.0% of all erythrocytes.
If bone marrow responding to anemia,
should see increases in retic count.
Newborns have higher retic count than
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 Bone Marrow
(In the Diagnosis of Anemia)

Bone marrow aspiration and biopsy

are important diagnostic tools in the
determination of anemia.

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 Other Tests
(In the Diagnosis of Anemia)

Hemoglobin Electrophoresis
Antiglobulin Testing
Osmotic Fragility
Sugar Water Test
Hams Test
RBC Enzymes
B12, Fe, TIBC, Folate Levels

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