understanding complete blood counts the abcs of cbcs

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Understanding Complete Blood Counts The ABCs of CBCs

Robert Miceli, MD

MetLife

2 For Financial Professional Use Only

The Good, The Bad, and The Ugly

Common Abnormal but Benign CBCs

(CBC may be accepted without repeat CBC or clinical evaluation)

• Mild iron deficiency anemia in pre-menopausal women

• Beta thalassemia minor

• Chronic benign neutropenia

• Reactive thrombocytosis

Abnormal / Worrisome CBCs

(may require additional follow-up or clinical evaluation)

• Iron deficiency anemia in men or post-menopausal women

• Mild or moderate anemia, not fully evaluated

• Unexplained thrombocytopenia or thrombocytosis

• Mild abnormalities involving all 3 cell lines (red cells, white cells, and platelets), mild pancytopenia

Markedly Abnormal CBCs

• Leukemia

• Severe anemia

• Severe leukopenia or severe pancytopenia


What Are the Major Components of Blood?

• Red Blood Cells (also called erythrocytes)

• White Blood Cells (also called leukocytes)

• Platelets (also called thrombocytes)

• Plasma


Fancy Words for High and Low

Cell Type Too High Too Low

Red Blood Cells (Erythrocytes)Erythrocytosis or

PolycythemiaAnemia

Platelets (Thrombocytes)Thrombocytosis or Thrombocythemia

Thrombocytopenia

White Blood Cells (Leukocytes) Leukocytosis Leukopenia

Neutrophils Neutrophilia Neutropenia

Lymphocytes Lymphocytosis Lymphopenia

Eosinophils Eosinophilia ---

Monocytes Monocytosis ---

Basophils Basophilia ---


Symptoms

Factor Too Much Too Little

RBCs Clots, strokesShortness of breath

(dyspnea), hypoxia, fatigue, pallor

WBCs Clots, strokes Infections

Platelets Clots, strokes Bleeding


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


How Are Blood Cells Formed?


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


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


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


White Blood Cells (WBCs)

• Neutrophils – also called a variety of other names on CBC reports, including:– polys

– PMNs

– segs

– grans

• Lymphocytes

• Monocytes

• Eosinophils

• Basophils


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


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


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 RESULT UNITS REF RANGE WBC 10.8 x 1000/mm3 3.9 - 11.1 RBC 3.73 L x 106/mm3 4.00 - 5.20 HGB 10.8 L g/dL 12.0 - 16.0 HCT 32.4 L % 38.5 - 49.0 MCV 84 fl 80 - 97 MCH 31.0 pg 27.5 - 33.5 MCHC 33.3 % 32.0 - 36.0 PLT 310 x 1000/mm3 150 - 350

• Paramedical exam: currently pregnant


“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.


Complete Blood Count (CBC)

TEST RESULT UNITS REF RANGE WBC 5.2 x 1000/mm3 3.9 - 11.1 RBC 3.81 L x 106/mm3 4.20 - 5.70 HGB 14.5 g/dL 13.2 - 16.9 HCT 41.2 % 38.5 - 49.0 MCV 98 H fl 80 - 97 MCH 33.7 H pg 27.5 - 33.5 MCHC 35.3 % 32.0 - 36.0 RDW 11.8 % 11.0 - 15.0 PLT 172 x 1000/mm3 140 - 390 MPV 7.6 fl 7.5 - 11.5 NEUT % 40.1 % 38.0 - 80.0 LYMPH % 46.1 % 15.0 - 49.0 MONO % 12.9 % 0.0 - 13.0 EOS % 0.6 % 0.0 - 8.0 BASO % 0.3 % 0.0 - 2.0 NEUT, ABS 2085 cells/mm3 1650 - 8000 LYMPH, ABS 2397 cells/mm3 1000 - 3500 MONO, ABS 671 cells/mm3 40 - 900 EOS, ABS 31 cells/mm3 30 - 600 BASO, ABS 16 cells/mm3 0 - 125


Red Blood Count and RBC Indices



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


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”



• 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”



• 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


Classification of Anemias Using MCV and RDW

Low MCV (Microcytic)

Normal MCV (Normocytic)

High MCV (Macrocytic)

Low RDW (low variability)

Thalassemia minor

Normal RDW

Thalassemia minor

Anemia of chronic disease

Anemia of chronic disease

Hereditary spherocytosis

Aplastic anemia

Myelodysplastic syndrome

High RDW (high variability)

Iron deficiency

Early deficiency of iron, B12, or folate

Sickle cell anemia

B12 or folate deficiency

Hemolytic anemia


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


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.


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


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


Case # 2

• 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

TEST RESULT UNITS REF RANGE

WBC 7.5 x 1000/mm3 3.9 - 11.1

RBC 3.46 L x 106/mm3 4.60 - 6.20

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 x 1000/mm3 140 - 390

NEUT % 58.0 % 40 - 79

LYMPH % 29.5 % 15 - 45

MONO % 7.0 % 0 - 11

EOS % 5.2 % 0 - 6 BASO % 0.3 % 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


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

• Hemoglobin improved with administration of iron

Iron-poor RBCs are pale and small (low MCV and MCH)


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


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


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


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


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


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


Case # 3

• 47 yo female applying for $1.5 million term

• Paramedical exam: all questions answered “no”

• Insurance labs normal

• Medical records: routine gynecologic visits, CBC done as part of routine exam last year


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

HCT 31.6 L

% 35.9 - 44.6

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


Underwriting Tip: Identifying β-thalassemia minor

Beta-Thalassemia Minor Iron Deficiency Anemia

• RBC count normal or high-normal, usually over 5

• RBC count low-normal or low, almost always less than 5

• Violates “Rule of 3s” (hemoglobin is less than 3 times the RBC count)

• Usually follows “Rule of 3s” (hemoglobin is roughly 3 times the 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


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


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


White Blood Count with Differential



Absolute Neutrophil Count


5.2 x 1000 = 5200

5200 x .401 = 2085


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.


• 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

Types of White Blood Cells - What’s the Diff?


WBC Differential: Neutrophils

Possible Causes of Neutrophilia:

Possible Causes of Neutropenia:

Common: bacterial infections, inflammatory disorders, stress, certain drugs (especially prednisone), pregnancy

Rare: leukemias

Common: chronic benign neutropenia (some forms are familial), chemotherapy

Uncommon: systemic lupus erythematosus, immunodeficiency states


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)


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


Case # 4

• 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.


WBC 2.8 L x 1000/mm3 3.9 - 11.1

RBC 5.02 x 106/mm3 4.20 - 5.70

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 x 1000/mm3 140 - 390

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

Total WBC x % Neutrophils = ANC

2800 x 50.2% = 1406


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.


WBC Differential: Lymphocytes

Possible Causes of Lymphocytosis:

Possible Causes of Lymphopenia:

Common: viral infections

Uncommon: inflammatory bowel disease

Rare: chronic lymphocytic leukemia, vasculitis

Uncommon: systemic lupus erythematosus, immunodeficiency states

Rare: aplastic anemia, Hodgkin’s disease


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

- - -


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

- - -


Case # 5

• 45 yo female applying for $1 million term

• Paramedical exam: asthma, usually well-controlled with inhalers

• Insurance labs: normal

• Medical records: records from primary care physician confirm that asthma is generally well-controlled, although she did require short-term prednisone in 2007. Also followed by a dermatologist for atopic dermatitis. Records include CBC from 9/08.


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

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 x 1000/mm3 140 - 390

NEUT % 45.1 % 38.0 - 80.0

LYMPH % 37.6 % 15.0 - 49.0

MONO % 5.3 % 0.0 - 13.0

EOS % 12.0 H % 0.0 - 8.0

BASO % 0.0 % 0.0 - 2.0

NEUT, ABS 3698 cells/mm3 1650 - 8000

LYMPH, ABS

3083 cells/mm3 1000 - 3500

MONO, ABS 435 cells/mm3 40 - 900

EOS, ABS 984 H cells/mm3 30 - 600

BASO, ABS 0 cells/mm3 0 - 125


Case # 6

• 45 yo male applying for $1 million term

• Paramedical exam: has seen personal physician for cold and cough, last visit 1 month ago


• 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.


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 40.2 % 38.5 - 49.0 MCV 96 fl 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 x 1000/mm3 140 - 390

NEUT % 40.1 % 38.0 - 80.0

LYMPH % 29.5 % 15.0 - 49.0

MONO % 9.5 % 0.0 - 13.0

EOS % 20.1 H % 0.0 - 8.0

BASO % 0.9 % 0.0 - 2.0

NEUT, ABS 3689 cells/mm3 1650 - 8000

LYMPH, ABS

2714 cells/mm3 1000 - 3500

MONO, ABS 874 cells/mm3 40 - 900

EOS, ABS 1850 H cells/mm3 30 - 600

BASO, ABS 83 cells/mm3 0 - 125


WBC Differential: Basophils

Possible Causes of Basophilia:

Decreased Levels:

Rare: leukemias, myeloid metaplasia, Hodgkin’s disease

- - -


Platelet Count



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


Selected Causes of Abnormal Platelet Counts

Possible Causes of Thrombocytosis:

Possible Causes of Thrombocytopenia:

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

Common: spurious lab result caused by platelet clumping, idiopathic or immune-mediated thrombocytopenia (ITP), medications, viral infection

Uncommon: hemolytic-uremic syndrome, leukemia, sepsis, hypersplenism


Case # 7

• 28 yo female applying for $100,000 term

• Paramedical exam: car accident 3 months ago


• Medical records: MVA 3 months ago with airbag deployment, two broken ribs and fractured foot.

TEST RESULT UNITS REF RANGE WBC 10.9 x 1000/mm3 3.9 - 11.1 RBC 4.4 x 106/mm3 4.20 - 5.70 HGB 13.5 g/dL 13.2 - 16.9 HCT 41.3 % 38.5 - 49.0 MCV 96 fl 80 - 97

MCH 33.6 H pg 27.5 - 33.5 MCHC 34.9 % 32.0 - 36.0 RDW 11.8 % 11.0 - 15.0 PLT 481 H x 1000/mm3 140 - 390 MPV 11.3 fl 7.5 - 11.5


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


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)


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)


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)


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


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


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


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 8/10 RESULT UNITS REF RANGE

WBC 7.0 5.4 4.7 L K/µL 4.8 - 10.8

RBC 4.37 L 3.97 L 3.82 L x 106/mm3 4.40 - 5.70

HGB 13.7 L 11.8 L 11.5 L g/dL 14.0 - 18.0

HCT 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 H 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 H % 2.0 - 10.0

EOS % 2.5 1.6 1.1 % 0.0 - 6.0

BASO % 0.5 0.5 0.4 % 0.0 - 2.0


Case # 8: CBCs dated 7/08, 1/10, 8/10

TEST 7/08 RESULT 1/10 RESULT 8/10 RESULT UNITS REF RANGE WBC 7.0 5.4 4.7 L K/µL 4.8 - 10.8 RBC 4.37 L 3.97 L 3.82 L x 106/mm3 4.40 - 5.70 HGB 13.7 L 11.8 L 11.5 L g/dL 14.0 - 18.0 HCT 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 H 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 H % 2.0 - 10.0 EOS % 2.5 1.6 1.1 % 0.0 - 6.0 BASO % 0.5 0.5 0.4 % 0.0 - 2.0


Q&A


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

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