©UFS
Understanding Complete Blood Counts
The ABCs of CBCs
Robert Miceli, MD
MetLife
The Good, The Bad, and The Ugly
• Mild iron deficiency anemia in pre-menopausal women
Common Abnormal but
Benign CBCs
• Beta thalassemia minor
(CBC may be accepted without
repeat CBC or clinical evaluation)
• Chronic benign neutropenia
• Reactive thrombocytosis
• Iron deficiency anemia in men or post-menopausal women
Abnormal / Worrisome CBCs
• Mild or moderate anemia, not fully evaluated
(may require additional follow-up
or clinical evaluation)
• Unexplained thrombocytopenia or thrombocytosis
• Mild abnormalities involving all 3 cell lines (red cells, white
cells, and platelets), mild pancytopenia
• Leukemia
Markedly Abnormal CBCs
• Severe anemia
• Severe leukopenia or severe pancytopenia
For Financial Professional Use Only
2
What Are the Major Components of Blood?
• Red Blood Cells
(also called erythrocytes)
• White Blood Cells
(also called leukocytes)
• Platelets
(also called thrombocytes)
• Plasma
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3
Fancy Words for High and Low
Cell Type
Too High
Too Low
Red Blood Cells (Erythrocytes)
Erythrocytosis or
Polycythemia
Anemia
Platelets (Thrombocytes)
Thrombocytosis or
Thrombocythemia
Thrombocytopenia
White Blood Cells (Leukocytes)
Leukocytosis
Leukopenia
Neutrophils
Neutrophilia
Neutropenia
Lymphocytes
Lymphocytosis
Lymphopenia
Eosinophils
Eosinophilia
---
Monocytes
Monocytosis
---
Basophils
Basophilia
---
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4
Symptoms
Factor
Too Much
Too Little
RBCs
Clots, strokes
Shortness of breath
(dyspnea), hypoxia, fatigue,
pallor
WBCs
Clots, strokes
Infections
Platelets
Clots, strokes
Bleeding
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5
Hematology Tests
• Specialized tests
– Bone Marrow aspiration and biopsy
• All of the formed elements of the blood
are produced primarily in the bone
marrow
• They are produced by progenitor cells –
cells which grow and differentiate into
mature formed elements
• This test can detect the lack or
overabundance of these progenitor cells,
and can find other problems such as
cancer
For Financial Professional Use Only
6
How Are Blood Cells Formed?
For Financial Professional Use Only
7
Red Blood Cells (RBCs)
• Largest cellular component of
blood, about 40-45% of blood
volume
• Comprised mostly of
hemoglobin
• Transport oxygen
• Red blood cells normally last
about 120 days before they
are removed by the spleen
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8
Hemoglobin
• Red pigment molecule which
gives RBCs (and blood) its
color
• Contains 4 molecules of heme
and 4 of globin (2 alpha chains
and 2 beta chains)
• Each molecule of heme
contains one iron ion
For Financial Professional Use Only
9
White Blood Cells
• There are several types of White Blood Cells
• They are all involved in immunity but in somewhat different ways
– Granulocytes (neutrophils, PMNs, polymorphonuclear leukocytes, or
“polys”) – involved in acute infections with bacteria. Immature form is
called a “band”
– Lymphocytes – involved in many types of infection, especially
viruses -Produce antibodies and “memory cells” - Are further
divided into T-cells and B-cells
– Eosinophils – involved in parasitic infections and allergies
– Basophils – involved in parasitic infections and allergies
– Monocytes – involved in bacterial and parasitic infections
For Financial Professional Use Only
10
White Blood Cells (WBCs)
• Neutrophils – also called a
variety of other names on
CBC reports, including:
–
–
–
–
polys
PMNs
segs
grans
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils
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11
Platelets
• Really more of a fragment of a
cell
– They are broken off from a
very large cell in the bone
marrow called a
megakaryocyte
– Primary function is to aid in
blood clotting
– Lifetime in the blood is 7-10
days after which they are
destroyed in the spleen
– Their clotting function is
permanently inhibited by
aspirin
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12
Plasma
• Plasma is the liquid
component of blood
• Comprised mostly of water,
but also includes:
– Protein (albumin, globulin,
fibrinogen)
– Lipids (cholesterol,
triglycerides)
– Dissolved salts and minerals
(sodium, calcium, potassium)
– Glucose
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13
Case # 1
• 32 yo female applying for $1 million whole life
• Insurance labs show elevations of total cholesterol at 240 and alkaline
phosphatase at 170, other labs are normal
• Medical records include CBC from 1 month prior to application, done during
routine office visit.
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
PLT
RESULT
10.8
3.73 L
10.8 L
32.4 L
84
31.0
33.3
310
UNITS
x 1000/mm3
x 106/mm3
g/dL
%
fl
pg
%
x 1000/mm3
REF RANGE
3.9 - 11.1
4.00 - 5.20
12.0 - 16.0
38.5 - 49.0
80 - 97
27.5 - 33.5
32.0 - 36.0
150 - 350
• Paramedical exam: currently pregnant
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14
“Anemia” of Pregnancy
• During pregnancy, the volume of red blood cells increases by
about 20%, but the plasma volume increases by 45%.
• Net result is ≈ 15% decrease in hemoglobin and hematocrit.
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15
Complete Blood Count (CBC)
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
NEUT %
LYMPH %
MONO %
EOS %
BASO %
NEUT, ABS
LYMPH, ABS
MONO, ABS
EOS, ABS
BASO, ABS
RESULT
5.2
3.81 L
14.5
41.2
98
H
33.7 H
35.3
11.8
172
7.6
40.1
46.1
12.9
0.6
0.3
2085
2397
671
31
16
UNITS
x 1000/mm3
x 106/mm3
g/dL
%
fl
pg
%
%
x 1000/mm3
fl
%
%
%
%
%
cells/mm3
cells/mm3
cells/mm3
cells/mm3
cells/mm3
For Financial Professional Use Only
REF RANGE
3.9 - 11.1
4.20 - 5.70
13.2 - 16.9
38.5 - 49.0
80 - 97
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
7.5 - 11.5
38.0 - 80.0
15.0 - 49.0
0.0 - 13.0
0.0 - 8.0
0.0 - 2.0
1650 - 8000
1000 - 3500
40 - 900
30 - 600
0 - 125
16
Red Blood Count and RBC Indices
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
NEUT %
LYMPH %
MONO %
EOS %
BASO %
NEUT, ABS
LYMPH, ABS
MONO, ABS
EOS, ABS
BASO, ABS
RESULT
5.2
3.81 L
14.5
41.2
98
H
33.7 H
35.3
11.8
172
7.6
40.1
46.1
12.9
0.6
0.3
2085
2397
671
31
16
UNITS
x 1000/mm3
x 106/mm3
g/dL
%
fl
pg
%
%
x 1000/mm3
fl
%
%
%
%
%
cells/mm3
cells/mm3
cells/mm3
cells/mm3
cells/mm3
For Financial Professional Use Only
REF RANGE
3.9 - 11.1
4.20 - 5.70
13.2 - 16.9
38.5 - 49.0
80 - 97
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
7.5 - 11.5
38.0 - 80.0
15.0 - 49.0
0.0 - 13.0
0.0 - 8.0
0.0 - 2.0
1650 - 8000
1000 - 3500
40 - 900
30 - 600
0 - 125
17
Measuring RBCs (and the “Rule of Threes”)
• Hematocrit (HCT) is the percent of a volume of whole blood occupied
by intact red blood cells. Measured in percent.
– Normal range for women: 36 - 46%
– Normal range for men: 41 - 53%
• Hemoglobin (HGB) measures the concentration of hemoglobin
expressed as grams of hemoglobin per deciliter (100 ml) of whole
blood.
– Normal range for women: 12 - 16 g/dL
– Normal range for men: 13.5 - 17.5 g/dL
• RBC count is the number of red blood cells per microliter of whole
blood. Measured in millions of RBCs per microliter of whole blood.
– Normal range for women: 4.0 - 5.2 x106/mm3
– Normal range for men: 4.5 - 5.9 x106/mm3
For Financial Professional Use Only
18
Red Blood Cell Indices
• Mean Corpuscular Volume (MCV) is the average size of red blood
cells.
– Normal range: 80-100 fL
– Low = “microcytic” (“too small”)
High = “macrocytic” (“too big”)
Normal = “normocytic” (“just right”)
• Red Cell Distribution Width (RDW) measures the variability in the
size of red blood cells.
– Normal range: 11.5-14.5%
– On a peripheral blood smear, high RDW is described as “anisocytosis”
• Mean Corpuscular Hemoglobin (MCH) is the amount of hemoglobin
in an average red blood cell.
– Normal range: 26-34 pg/cell
• Mean Corpuscular Hemoglobin Concentration (MCHC) is the
average concentration of hemoglobin in an average RBC.
– Normal range: 31-37 g/dL
– “Hypochromic” = “too pale”
“Normochromic” = “just right”
For Financial Professional Use Only
19
Red Blood Cell Indices
• Mean Corpuscular Volume (MCV) is the average size of red blood
cells.
– Normal range: 80-100 fL
– Low = “microcytic” (“too small”)
High = “macrocytic” (“too big”)
Normal = “normocytic” (“just right”)
• Red Cell Distribution Width (RDW) measures the variability in the
size of red blood cells.
– Normal range: 11.5-14.5%
– On a peripheral blood smear, high RDW is described as “anisocytosis”
• Mean Corpuscular Hemoglobin (MCH) is the amount of hemoglobin
in an average red blood cell.
– Normal range: 26-34 pg/cell
• Mean Corpuscular Hemoglobin Concentration (MCHC) is the
average concentration of hemoglobin in an average RBC.
– Normal range: 31-37 g/dL
– “Hypochromic” = “too pale”
“Normochromic” = “just right”
For Financial Professional Use Only
20
Red Blood Cell Indices
• Mean Corpuscular Volume (MCV) is the average size of
red blood cells.
– If anemia is present, MCV is a useful tool to guide further testing
– If anemia is not present, MCV is of little value:
• Low MCV without anemia suggests thalassemia minor (trait)
• High MCV without anemia can be caused by certain medications
(Dilantin, oral contraceptives, methotrexate) and is a “soft” marker
of possible alcohol overuse
• Red Cell Distribution Width (RDW) measures the
variability in the size of red blood cells.
– Not useful in the absence of anemia
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21
Classification of Anemias Using MCV and RDW
Low MCV
(Microcytic)
Low RDW
(low variability)
High RDW
(high variability)
High MCV
(Macrocytic)
Anemia of chronic
disease
Aplastic anemia
Thalassemia minor
Thalassemia minor
Normal RDW
Normal MCV
(Normocytic)
Anemia of chronic
disease
Iron deficiency
Hereditary
spherocytosis
Myelodysplastic
syndrome
Early deficiency of
iron, B12, or folate
B12 or folate
deficiency
Sickle cell anemia
Hemolytic anemia
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22
Descriptive Terms Used on Peripheral Smears
• Anisocytosis: marked variation in RBC sizes (visual
counterpart of increased RDW)
• Hypochromia or hypochromasia: RBCs are paler than
normal because they contain less hemoglobin (visual
counterpart of decreased MCH)
• Macrocytosis: increased number of large RBCs (visual
counterpart of increased MCV)
• Microcytosis: increased number of small RBCs (visual
counterpart of decreased MCV)
• Poikilocytosis: marked variation in the shape of RBCs
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23
Reticulocyte Count
• Reticulocytes are “young” red blood cells that
were recently released from the bone marrow.
• Normally, reticulocytes comprise 0.5 - 2.5% of all
red blood cells.
• Increased reticulocytes (reticulocytosis) is a
normal response to blood loss or anemia. Since
reticulocytes are larger, the MCV (and RDW)
may be elevated.
• The combination of anemia with a low or normal
reticulocyte count indicates that the bone
marrow is unable to respond normally, either
due to lack of essential ingredients (iron
deficiency, vitamin B12 or folate deficiency),
bone marrow disease, or chronic disease.
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24
Anemia
• Low RBCs – two ways to get there: Too little production, or increased destruction
• Low production
– Aplastic anemia (no production)
– Iron Deficiency Anemia
• Increased Destruction
– Hemolytic anemia
– Spherocytosis
– Hemoglobin disorders (thalassemia, sickle cell, others)
– Hemorrhage (blood loss)
– Hypersplenism (an overactive spleen which destroys formed elements
prematurely)
• Regardless of the type of anemia, once the level of hemoglobin/hematocrit gets
sufficiently low, mortality may result
• Mortality Concerns
– Severe anemia may cause a critical lack of oxygen to the brain or heart
– Less severe anemia may still worsen chronic heart or lung conditions
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25
Iron deficiency/hemorrhagic anemia
• The oxygen-carrying protein heme contains iron, and gives blood its red color
• If iron levels are low, RBCs cannot be produced fast enough to match losses
• Iron-deficiency anemia is the most common form of anemia world-wide
– May be due to poor intake of iron or chronic loss of blood
– Blood is lost most commonly from the GI tract
• The most important factor to consider when underwriting this condition is –
What is the cause?
– Possibilities include
• Stomach ulcers
• Colon cancer
• Vascular malformations in the GI tract
• Endometrial cancer
• Recent surgery or trauma
• Multiple blood donations
• Can be treated with iron supplements, blood transfusion and/or eradication of the
cause
For Financial Professional Use Only
26
Case # 2
TEST
• 57 yo male applying for
$250,000 whole life
• Paramedical exam: mild type 2
diabetes, controlled on oral
medications, HbA1c 6.1%
• APS: routine follow-up for
diabetes, no complications,
CBC done as routine test
RESULT
WBC
7.5
UNITS
x 1000/mm3
x
106/mm3
REF RANGE
3.9 - 11.1
RBC
3.46 L
HGB
10.1 L
g/dL
14.0 - 18.0
HCT
29.6 L
%
40.0 - 54.0
MCV
85.6
fl
80 – 94
MCH
29.3
pg
27 - 33
MCHC
34.2
%
32.0 - 36.0
RDW
13.9
%
11.0 - 15.0
PLT
222
NEUT %
58.0
%
40 - 79
LYMPH %
29.5
%
15 - 45
MONO %
7.0
%
0 - 11
EOS %
BASO %
5.2
0.3
%
%
0-6
0-3
NEUT, #
4.4
x103 uL
1.8 - 8.7
LYMPH, #
2.2
x103 uL
0.7 - 5.0
MONO, #
0.5
x103 uL
0.0 - 1.2
EOS, #
0.4
x103 uL
0.0 - 0.7
BASO, #
0
x103 uL
0.0 - 0.3
For Financial Professional Use Only
x
1000/mm3
4.60 - 6.20
140 - 390
27
Case # 2 (continued)
• Serum vitamin B12 and folate
levels were normal
• Iron studies showed low serum
ferritin and a low transferrin
saturation, consistent with iron
deficiency
• Colonoscopy was normal
• Upper endoscopy showed
moderate gastritis and
esophagitis with no evidence of
active bleeding
Iron-poor RBCs are pale and small
(low MCV and MCH)
• Hemoglobin improved with
administration of iron
For Financial Professional Use Only
28
Megaloblastic Anemia
• A diverse group of anemias, all of which show elevated MCV on the blood count
• May be caused by:
– Vitamin deficiency (usually B12 or folic acid)
– Alcohol intake (moderately high levels)
– Leukemia (WBCs would be abnormal, too)
– Certain medications
• Pernicious anemia – vitamin B12 deficiency caused by an inability to absorb the
vitamin from the GI tract. May cause neuropathy, weakness, or even psychiatric
problems
• Usually treated by
– Determining and eliminating the cause
– Correcting the vitamin deficiency (if any)
• May require injections of vitamin B12 if the cause is pernicious anemia
• Mortality concerns – determined by the underlying cause and severity of anemia
For Financial Professional Use Only
29
Autoimmune Hemolytic Anemia
• A condition where the immune system attacks and destroys red blood
cells
• Two forms:
– Warm antibody
– Cold Agglutinin disease
• Both cause:
– Normocytic anemia with antibodies against red blood cells (positive
Coomb’s test)
• Mortality concerns
– Severity of anemia (hemolytic crises may be fatal)
– Presence of an underlying cause (such as infection or rheumatologic
disease – like rheumatoid arthritis)
– Need for side-effect prone treatments such as steroids,
immunosuppressants, or frequent blood transfusions
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30
Hereditary Spherocytosis/Elliptocytosis
• A disorder of red cell shape where the misshapen cells are
taken up by the spleen and destroyed prematurely
• Leads to anemia and splenomegaly
• Splenectomy will normalize the blood count and resolve the
anemia, but the cells will still be misshapen
• Mortality Concerns:
– Severity of hemolysis or anemia
– Overwhelming infection after splenectomy
For Financial Professional Use Only
31
Anemia of Chronic Disease
• Also known as anemia of chronic inflammation
• May occur in association with a wide variety of chronic
diseases, especially inflammatory conditions, chronic
infection, liver disease, congestive heart failure, diabetes,
and cancer.
• Anemia is usually mild (Hgb 9-12, Hct 27-35), but can be
lower in about 20% of cases.
• MCV is usually normal or low normal
• Platelets may be elevated, especially if inflammation is
prominent
For Financial Professional Use Only
32
Hemoglobin Disorders
• These are various, largely genetic, disorders which affect
hemoglobin
• Those which affect globin:
– Thalassemias
– Sickle cell and related disorders
• Those which affect heme:
– Porphyrias
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33
Thalassemias
• Inherited disorders of the globin gene leading to low levels of alpha or beta globin chains
• Fatalities are unusual in all but the most severe forms
• Alpha Thalassemia: Beta Thalassemia major
– Hemoglobin H disease
– Alpha Thalassemia Trait
• Beta Thalassemia:
– Beta Thalassemia major
– Beta Thalassemia intermedia
– Beta Thalassemia minor (trait)
• Prevalence as high as 10% in Mediterranean, African, and Southeast Asian
populations
• Typically mild anemia with marked microcytosis
• Can coexist with other hemoglobin abnormalities, with increased severity of the
anemia and increased mortality concern, but true beta-thalassemia minor (trait)
has no excess mortality concerns
For Financial Professional Use Only
34
Case # 3
• 47 yo female applying for $1.5
million term
• Paramedical exam: all
questions answered “no”
TEST
RESULT
UNITS
REF RANGE
WBC
4.7
x 109/L
4.4 - 11.3
RBC
5.6
x 1012/L
4.7 - 6.1
HGB
10.5
L
g/dL
12.3 - 15.3
• Insurance labs normal
HCT
31.6
L
%
35.9 - 44.6
• Medical records: routine
gynecologic visits, CBC done
as part of routine exam last
year
MCV
65.8
L
fL
80 - 96
MCH
19.9
L
pg
27.5 - 33.2
MCHC
26.7
L
%
33.4 - 35.5
RDW
13.0
%
11.5 - 14.5
PLT
249
x 109/L
100 - 450
For Financial Professional Use Only
35
Underwriting Tip: Identifying β-thalassemia minor
Beta-Thalassemia Minor
• RBC count normal or highnormal, usually over 5
Iron Deficiency Anemia
• RBC count low-normal or low,
almost always less than 5
• Violates “Rule of 3s”
• Usually follows “Rule of 3s”
(hemoglobin is less than 3 times (hemoglobin is roughly 3 times the
the RBC count)
RBC count)
• MCV usually quite low (60-70)
even when anemia is mild
• MCV doesn’t become that low
unless anemia is quite severe
• RDW is usually normal or low
• RDW is often high
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36
Sickle Cell Disease
• Forms of hemoglobin:
– “A” – adult normal hemoglobin
– “S” – sickle cell hemoglobin
– “C” – mutant hemoglobin, but with a different result
• Since each person has 2 genes, several combinations are possible
– “SA” – Sickle trait, may have minimal sickle cell formation, but
otherwise is basically a carrier
– “SS” – affected with sickle cell disease can be mild to severe
– “SC” – similar to SS but milder
– “CC”- similar to SS but quite a bit milder
Sickle Cell Disease:
• When oxygen level is low, RBCs assume a sickle shape, and block
capillaries, leading to severe bone pain, and infarctions in various organs
• Death can occur from infection,
severe
anemia,
stroke or heart attack
For Financial
Professional
Use Only
37
Porphyria
• A large variety of genetic disorders which affect the
biosynthesis of heme
• All are rare
• May cause episodes of severe abdominal pain, sensitivity
to sunlight, even psychiatric problems or paralysis
• Mortality Concerns
– Fatalities are quite rare, may occur in the most severe case
For Financial Professional Use Only
38
White Blood Count with Differential
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
NEUT %
LYMPH %
MONO %
EOS %
BASO %
NEUT, ABS
LYMPH, ABS
MONO, ABS
EOS, ABS
BASO, ABS
RESULT
5.2
3.81 L
14.5
41.2
98
H
33.7 H
35.3
11.8
172
7.6
40.1
46.1
12.9
0.6
0.3
2085
2397
671
31
16
UNITS
x 1000/mm3
x 106/mm3
g/dL
%
fl
pg
%
%
x 1000/mm3
fl
%
%
%
%
%
cells/mm3
cells/mm3
cells/mm3
cells/mm3
cells/mm3
For Financial Professional Use Only
REF RANGE
3.9 - 11.1
4.20 - 5.70
13.2 - 16.9
38.5 - 49.0
80 - 97
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
7.5 - 11.5
38.0 - 80.0
15.0 - 49.0
0.0 - 13.0
0.0 - 8.0
0.0 - 2.0
1650 - 8000
1000 - 3500
40 - 900
30 - 600
0 - 125
39
Absolute Neutrophil Count
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
NEUT %
LYMPH %
MONO %
EOS %
BASO %
NEUT, ABS
LYMPH, ABS
MONO, ABS
EOS, ABS
BASO, ABS
RESULT
5.2
3.81 L
14.5
41.2
98
H
33.7 H
35.3
11.8
172
7.6
40.1
46.1
12.9
0.6
0.3
2085
2397
671
31
16
UNITS
x 1000/mm3
x 106/mm3
g/dL
%
fl
pg
%
%
x 1000/mm3
fl
%
%
%
%
%
cells/mm3
cells/mm3
cells/mm3
cells/mm3
cells/mm3
REF RANGE
3.9 - 11.1
4.20 - 5.70
13.2 - 16.9
38.5 - 49.0
80 - 97
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
7.5 - 11.5
38.0 - 80.0
15.0 - 49.0
0.0 - 13.0
0.0 - 8.0
0.0 - 2.0
1650 - 8000
1000 - 3500
40 - 900
30 - 600
0 - 125
5.2 x 1000 = 5200
5200 x .401 = 2085
For Financial Professional Use Only
40
Underwriting Tip
• If the total white blood count (WBC) is normal, the red cells
and platelets are normal, and your applicant is otherwise
healthy, don’t worry about the differential white blood count,
especially if the absolute counts are normal.
• The percentage of neutrophils, lymphocytes, etc. often
fluctuate in response to an infection; this is not a big
underwriting concern.
For Financial Professional Use Only
41
Types of White Blood Cells - What’s the Diff?
• Neutrophils – also called a
variety of other names on CBC
reports, including:
–
–
–
–
polys
PMNs
segs
bands or stabs (immature
neutrophils indicate acute
infection)
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils
For Financial Professional Use Only
42
WBC Differential: Neutrophils
Possible Causes of
Neutrophilia:
Common: bacterial infections,
inflammatory disorders, stress,
certain drugs (especially
prednisone), pregnancy
Rare: leukemias
Possible Causes of
Neutropenia:
Common: chronic benign
neutropenia (some forms are
familial), chemotherapy
Uncommon: systemic lupus
erythematosus, immunodeficiency
states
For Financial Professional Use Only
43
Leukocytosis
• An elevated WBC count is termed “leukocytosis”
• Normal level is 4,400 to 10,000 WBC per mm3
• This can result from many causes, principally infections,
inflammatory disorders, and medications
• Cancer and myeloproliferative disorders can also cause
high, sometimes extremely high, WBC counts
• Treatment is aimed at the underlying cause
• Death may result from the underlying cause such as severe
infection or cancer (leukemia)
For Financial Professional Use Only
44
Neutropenia
• The relative lack of neutrophils (the most common type of WBC, also called
granulocytes)
• Normally humans have at least 1500 neutrophils/mm3
• Severe neutropenia (almost no neutrophils) is “agranulocytosis”
• May be cause by gene defects, various drugs, or medical conditions
• Treatment is usually aimed at the underlying cause
• Some may require antibiotics to prevent infection or medications to stimulate
production of neutrophils
• Death may occur due to overwhelming infection
Chronic Benign Neutropenia:
• Overall risk of infection is low, usually asymptomatic
• Two forms – familial and non-familial
• Key features from underwriting perspective are the absence of significant infections
and stability over time
For Financial Professional Use Only
45
Case # 4
TEST
• 44 yo male applying for
$2,000,000 whole life
• Paramedical exam: rotator cuff
injury to right shoulder, getting
physical therapy, elevated
cholesterol on Lipitor
• Insurance labs are normal
• Medical records only included
labs, no office notes.
RESULT
WBC
2.8
UNITS
L x
REF RANGE
1000/mm3
x 106/mm3
3.9 - 11.1
RBC
5.02
HGB
14.9
g/dL
13.2 - 16.9
HCT
45.2
%
38.5 - 49.0
MCV
95
fl
80 - 97
MCH
34.0 H
pg
27.5 - 33.5
MCHC
35.1
%
32.0 - 36.0
RDW
13.8
%
11.0 - 15.0
PLT
212
NEUT %
50.2
%
38.0 - 80.0
LYMPH %
36.0
%
15.0 - 49.0
MONO %
13.3
%
0.0 - 13.0
EOS %
0.3
%
0.0 - 8.0
BASO %
0.2
%
0.0 - 2.0
x 1000/mm3
4.20 - 5.70
140 - 390
Total WBC x % Neutrophils =
ANC
2800 x 50.2% = 1406
For Financial Professional Use Only
46
Case # 4: Additional Information
• Office notes arrive for review with no history of recurrent or
serious infections, and WBC has been stable in 2.5 - 4.0
range for the past 5 years. Absolute neutrophil counts are
always greater than 1000.
For Financial Professional Use Only
47
WBC Differential: Lymphocytes
Possible Causes of
Lymphocytosis:
Common: viral infections
Possible Causes of
Lymphopenia:
Uncommon: inflammatory bowel
disease
Uncommon: systemic lupus
erythematosus, immunodeficiency
states
Rare: chronic lymphocytic
leukemia, vasculitis
Rare: aplastic anemia, Hodgkin’s
disease
For Financial Professional Use Only
48
WBC Differential: Monocytes
Possible Causes of
Monocytosis:
Decreased Levels:
Common: recovery phase after
infections
Uncommon: certain infections (TB,
malaria), inflammatory bowel
disease
---
Rare: myeloproliferative disorders
including myeloid metaplasia,
polycythemia vera, certain forms of
leukemia and lymphoma
For Financial Professional Use Only
49
WBC Differential: Eosinophils
Possible Causes of
Eosinophilia:
Decreased Levels:
Common: allergic disorders
(including drug reactions)
Uncommon: parasite infection,
lupus, rheumatoid arthritis
---
Rare: hypereosinophilic syndrome,
diffuse skin diseases, some forms
of leukemia and lymphoma,
Löffler’s endocarditis
For Financial Professional Use Only
50
Case # 5
TEST
RESULT
UNITS
REF RANGE
• 45 yo female applying for $1
million term
WBC
8.2
x 1000/mm3
3.9 - 11.1
RBC
4.5
x 106/mm3
4.2 - 5.7
HGB
13.0
g/dL
12.0 - 16.0
• Paramedical exam: asthma,
usually well-controlled with
inhalers
HCT
40.5
%
36.0 - 46.0
MCV
94
fl
80 - 97
MCH
28.0
pg
27.5 - 33.5
MCHC
34.0
%
32.0 - 36.0
RDW
13.4
%
11.0 - 15.0
PLT
372
NEUT %
45.1
%
38.0 - 80.0
LYMPH %
37.6
%
15.0 - 49.0
MONO %
5.3
%
0.0 - 13.0
%
0.0 - 8.0
• Insurance labs: normal
• Medical records: records from
primary care physician confirm
that asthma is generally wellcontrolled, although she did
require short-term prednisone in
2007. Also followed by a
dermatologist for atopic
dermatitis. Records include CBC
from 9/08.
EOS %
12.0
x 1000/mm3
H
140 - 390
BASO %
0.0
%
0.0 - 2.0
NEUT, ABS
3698
cells/mm3
1650 - 8000
LYMPH,
ABS
MONO, ABS
3083
cells/mm3
1000 - 3500
435
cells/mm3
40 - 900
cells/mm3
30 - 600
cells/mm3
0 - 125
EOS, ABS
BASO, ABS
For Financial Professional Use Only
984
0
H
51
Case # 6
TEST
• 45 yo male applying for $1 million
term
• Paramedical exam: has seen
personal physician for cold and
cough, last visit 1 month ago
• Insurance labs: normal
• Medical records: seen in January,
March, and August of this year
complaining of non-productive cough
since December 2008. Chest x-ray
showed questionable vague infiltrates
in both lung bases. Did not improve
with 2 courses of antibiotics or
therapeutic trial of asthma inhalers.
Upper GI series and upper endoscopy
showed no evidence of GERD. On
August visit, also noted fatigue and
diarrhea.
RESULT
UNITS
REF RANGE
WBC
9.2
x 1000/mm3
3.9 - 11.1
RBC
4.2
x 106/mm3
4.20 - 5.70
HGB
13.3
g/dL
13.2 - 16.9
HCT
MCV
40.2
96
%
fl
38.5 - 49.0
80 - 97
MCH
32.0
pg
27.5 - 33.5
MCHC
35.3
%
32.0 - 36.0
RDW
11.8
%
11.0 - 15.0
PLT
390
NEUT %
40.1
%
38.0 - 80.0
LYMPH %
29.5
%
15.0 - 49.0
MONO %
9.5
%
0.0 - 13.0
%
0.0 - 8.0
0.9
%
0.0 - 2.0
NEUT, ABS
3689
cells/mm3
1650 - 8000
LYMPH,
ABS
MONO, ABS
2714
cells/mm3
1000 - 3500
874
cells/mm3
40 - 900
EOS, ABS
1850 H
cells/mm3
30 - 600
BASO, ABS
83
cells/mm3
0 - 125
EOS %
BASO %
For Financial Professional Use Only
20.1
x 1000/mm3
H
140 - 390
52
WBC Differential: Basophils
Possible Causes of Basophilia:
Decreased Levels:
Rare: leukemias, myeloid
metaplasia, Hodgkin’s disease
For Financial Professional Use Only
---
53
Platelet Count
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
NEUT %
LYMPH %
MONO %
EOS %
BASO %
NEUT, ABS
LYMPH, ABS
MONO, ABS
EOS, ABS
BASO, ABS
RESULT
5.2
3.81 L
14.5
41.2
98
H
33.7 H
35.3
11.8
172
7.6
40.1
46.1
12.9
0.6
0.3
2085
2397
671
31
16
UNITS
x 1000/mm3
x 106/mm3
g/dL
%
fl
pg
%
%
x 1000/mm3
fl
%
%
%
%
%
cells/mm3
cells/mm3
cells/mm3
cells/mm3
cells/mm3
For Financial Professional Use Only
REF RANGE
3.9 - 11.1
4.20 - 5.70
13.2 - 16.9
38.5 - 49.0
80 - 97
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
7.5 - 11.5
38.0 - 80.0
15.0 - 49.0
0.0 - 13.0
0.0 - 8.0
0.0 - 2.0
1650 - 8000
1000 - 3500
40 - 900
30 - 600
0 - 125
54
Mean Platelet Volume (MPV)
• “Young” platelets, recently released from the bone marrow,
are typically slightly larger
• Often elevated in immune or idiopathic thrombocytopenic
purpura (ITP)
• In an individual with low platelet count (thrombocytopenia):
– Increased MPV indicates normal bone marrow response
– Decreased or low normal MPV may indicate impaired bone
marrow response
For Financial Professional Use Only
55
Selected Causes of Abnormal Platelet Counts
Possible Causes of
Thrombocytosis:
Common: “Reactive” thrombocytosis
related to acute trauma, surgery,
blood loss, iron deficiency, chronic
infections (osteomyelitis),
inflammatory diseases including
rheumatoid arthritis and ulcerative
colitis, splenectomy
Uncommon: polycythemia vera,
essential thrombocytosis (plt count
over 600,000), some cancers
Possible Causes of
Thrombocytopenia:
Common: spurious lab result
caused by platelet clumping,
idiopathic or immune-mediated
thrombocytopenia (ITP),
medications, viral infection
Uncommon: hemolytic-uremic
syndrome, leukemia, sepsis,
hypersplenism
For Financial Professional Use Only
56
Case # 7
• 28 yo female applying for
$100,000 term
• Paramedical exam: car
accident 3 months ago
• Insurance labs: normal
• Medical records: MVA 3
months ago with airbag
deployment, two broken ribs
and fractured foot.
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
RESULT
10.9
4.4
13.5
41.3
96
UNITS
REF RANGE
x 1000/mm3
3.9 - 11.1
6
3
x 10 /mm
4.20 - 5.70
g/dL
13.2 - 16.9
%
38.5 - 49.0
fl
80 - 97
33.6 H
pg
34.9
%
11.8
%
481 H x 1000/mm3
11.3
fl
For Financial Professional Use Only
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
7.5 - 11.5
57
Idiopathic Thrombocytopenic Purpura (ITP)
• Although there are many causes of low platelet counts, including
medications, infections, and hypersplenism, the term “ITP” is reserved
for the autoimmune destruction of platelets; “Immune thrombocytopenic
purpura”
• Immune system attacks and destroys platelets faster than they can be
produced; red rash (purpura) and bleeding
• Some cases will remit with this alone and never recur
• If more severe, can usually be cured with splenectomy, but some will
still have low platelets after splenectomy
• Prognosis depends on the current platelet count and the mode of
treatment
• Mortality Concerns
– Fatalities may occur due to severe bleeding or due to overwhelming
infection after splenectomy
For Financial Professional Use Only
58
Bone Marrow Disorders
• All formed elements of the blood are made primarily in the bone marrow
• There is particular concern if all 3 cell lines are abnormal (RBCs, WBCs, and platelets),
especially if:
– the applicant is over age 50 and/or
– there is an increased percentage of monocytes
• This suggests the possibility of diseases involving the bone marrow, and many of these
diseases have very significant mortality concerns.
• Aplastic Anemia: diminished-absent precursor cells (pancytopenia)
• Myeloproliferative disorders: bone marrow cells grow too rapidly with over-production
of blood cells and/or platelets
– If this acceleration continues it may transform into cancer (usually leukemia)
– Myeloproliferative disorders include:
• Essential thrombocytosis
• Polycythemia vera
• Myelofibrosis (possible pancytopenia)
• Myelodysplastic syndromes: ineffective blood cell production (pancytopenia)
For Financial Professional Use Only
59
Aplastic Anemia
• A disorder where the bone marrow stops producing blood
cells (pancytopenia - all lines – RBC, WBC and platelets)
• Can be congenital (Fanconi anemia), or acquired
• Acquired form brought on by certain infections or drugs
• Prognosis depends on severity – most cases pose a very
high mortality risk unless spontaneously remitted long ago
• Mortality Concerns:
– The aplastic crisis may result in death due to infection,
bleeding, or severe anemia
– Complications of bone marrow transplant (graft vs. host
disease)
For Financial Professional Use Only
60
Essential Thrombocytosis (ET)
• Also called essential thrombocythemia
• Megakaryocytes in the bone marrow produce too many
platelets, which may be misshapen or may function poorly
• They may become so numerous as to cause clotting (risk
of stroke)
• Platelet count at least 600k up to 1.5 million per mm3
• Prognosis depends on frequency of bleeding/clotting
complications
• Also, increased risk for developing leukemia, especially
chronic myelogenous leukemia (CML)
For Financial Professional Use Only
61
Polycythemia (rubra) vera
• Red cell progenitors start to lose control over their growth
• Can be treated with phlebotomy (removing blood) or
marrow-suppressing medications
• Mortality Concerns
– Fatalities can occur due to clotting, or due to
malignant transformation
For Financial Professional Use Only
62
Myelofibrosis
• A condition where the bone marrow becomes fibrotic
(scarred)
• Can cause low counts of all cell lines (pancytopenia)
• Spleen and liver may become enlarged as they begin to
serve as back-up producers of formed elements
(extramedullary hematopoesis)
• Mortality Concerns: Decreasing counts of all formed
elements may lead to death from infection, severe anemia,
or bleeding
For Financial Professional Use Only
63
Myelodysplasia
• A bone marrow disorder of older individuals, where there is
ineffective production of red blood cells, eventually may
also involve the WBC and platelet lines (pancytopenia)
• Can be a precursor to leukemia
• Several subtypes, e.g., refractory anemia (RA) or refractory
anemia with ringed sideroblasts (RARS)
• Treatment is supportive – transfusions and antibiotics
• Prognosis is generally poor
• Mortality Concerns: malignant transformation, severe
anemia, infection, or bleeding
For Financial Professional Use Only
64
Case # 8
76 yo male applying for $2 million UL
• MD exam: type 2 diabetes, on Avandia
• Insurance labs: glucose 118, hemoglobin A1c 7.9%
• Medical records: mild anemia, normal iron studies, B12 and folate levels normal, no history of
alcohol excess
TEST
7/08 RESULT
1/10 RESULT
WBC
7.0
RBC
4.37
L
3.97
HGB
13.7
L
HCT
5.4
8/10 RESULT
UNITS
REF RANGE
4.7
L
K/µL
4.8 - 10.8
L
3.82
L
x 106/mm3
4.40 - 5.70
11.8
L
11.5
L
g/dL
14.0 - 18.0
42.1
35.4
L
34.4
L
%
42.0 - 52.0
MCV
96.9
101.2 H
102.2 H
fl
80 - 97
MCH
33.0
33.6
33.1
pg
27.5 - 33.5
MCHC
33.2
33.0
32.9
%
32.0 - 36.0
RDW
13.8
14.9
14.3
%
11.0 - 15.0
PLT
241
199
129
L
K/µL
140 - 390
MPV
8.9
9.0
8.3
L
fl
8.6 - 11.7
NEUT %
55.0
61.0
55.6
%
30.0 - 75.0
LYMPH %
34.8
27.7
31.7
%
10.0 - 50.0
MONO %
7.2
9.2
11.2
%
2.0 - 10.0
EOS %
2.5
1.6
1.1
%
0.0 - 6.0
BASO %
0.5
0.5
0.4
For
Financial Professional
Use Only
%
0.0 - 2.0
H
H
65
Case # 8: CBCs dated 7/08, 1/10, 8/10
TEST
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
PLT
MPV
NEUT %
LYMPH %
MONO %
EOS %
BASO %
7/08 RESULT
7.0
4.37 L
13.7 L
42.1
96.9
33.0
33.2
13.8
241
8.9
55.0
34.8
7.2
2.5
0.5
1/10 RESULT
5.4
3.97 L
11.8 L
35.4 L
101.2 H
33.6 H
33.0
14.9
199
9.0
61.0
27.7
9.2
1.6
0.5
8/10 RESULT
4.7
L
3.82 L
11.5 L
34.4 L
102.2 H
33.1
32.9
14.3
129
L
8.3
L
55.6
31.7
11.2 H
1.1
0.4
For Financial Professional Use Only
UNITS
K/µL
x 106/mm3
g/dL
%
fl
pg
%
%
K/µL
fl
%
%
%
%
%
REF RANGE
4.8 - 10.8
4.40 - 5.70
14.0 - 18.0
42.0 - 52.0
80 - 97
27.5 - 33.5
32.0 - 36.0
11.0 - 15.0
140 - 390
8.6 - 11.7
30.0 - 75.0
10.0 - 50.0
2.0 - 10.0
0.0 - 6.0
0.0 - 2.0
66
Q&A
For Financial Professional Use Only
67
Life insurance products are issued by MetLife Investors USA Insurance Company, Metropolitan Life Insurance Company
and in New York only, by First MetLife Investors Insurance Company. All guarantees are based on the claims-paying
ability and financial strength of the issuing insurance company. Variable products are distributed by MetLife Investors
Distribution Company (MetLife Investors), Irvine, CA. September 2012
L0911208105[exp0912][All States][DC,GU,MP,PR,VI]
For Financial Professional Use Only
68