Complete Blood Count (CBC) & Red Cell Morphology

LoAnn Peterson, M.D., Yi-Hua Chen, M.D.

Division of Hematopathology, Department of Pathology,
Northwestern University Feinberg School of Medicine
 Blood Component
• Blood is a fluid connective tissue constituting ~7% (~5 liters) of
total human body weight. The peripheral blood allows us a
“window” into the functional and biologic status of a patient.

Water (93%)

Plasma
(~55%) Protein (such as albumin, globulin, fibrinogen)

RBC Others: glucose, electrolytes, clotting factors,

Blood components
(~45%) hormones, amino acids, vitamins, etc

Plasma
WBC & Platelet
WBC

RBC
Complete Blood Count (CBC)
 NMH Hematology Lab

CBC with differential is one of the most common laboratory tests performed
 Complete Blood Count (CBC)
• CBC component: • Differential:
– White blood cell (WBC) count – The percentage (%) of each WBC

– Red blood cell (RBC) subtype of total WBC

• RBC count – The absolute count of each WBC

• Hemoglobin (Hb) subtype per microliter (mL)
• Hematocrit (HCT) WBC:
• Mean corpuscular volume (MCV) • Neutrophils
• Mean corpuscular hemoglobin (MCH) • Lymphocytes
• Mean corpuscular hemoglobin • Monocytes
concentration (MCHC)
• Eosinophils
• RBC distribution width (RDW)
• Basophils
– Platelet count
 A standard report of CBC with differential
CBC
Test Result Unit *Reference Range
White blood cell count 11.0 H K/mL [3.5-10.5]
Red cell count 4.49 M/mL [4.30-5.80]
Hemoglobin (HGB) 14.4 g/dL [13.0-17.5]
Hematocrit (HCT) 42.4 % [38.0-50.0]
MCV 94 FL** [80-99]
MCH 32.1 Pg** [27.0-34.0]
MCHC 34.0 % [32.0-35.5]
RDW 13.1 % [11.0-15.0]
Platelet count 271 K/mL ** [140-390]

Differential
Test Result Unit Reference Range
Neutrophils 36 % [34-73]
Lymphocytes 53 H % [15-50]
Monocytes 9 % [5-15]
Eosinophils 2 % [0-8]
Basophils 0 % [0-2]
Absolute Neutrophils 4.0 K/mL [1.5-8.0]
Absolute Lymphocytes 5.8 H K/mL [1.0-4.0]
Absolute Monocytes 1.0 K/mL [0.2-1.0]
Absolute Eosinophils 0.2 K/mL [0.0-0.6]
Absolute Basophils 0.2 K/mL [0.0-0.2]
 Complete Blood Count (CBC)
CBC
Test Result Unit *Reference Range
White blood cell count 11.0 H K/mL [3.5-10.5]
Red cell count 4.49 M/mL [4.30-5.80]
Hemoglobin (HGB) 14.4 g/dL [13.0-17.5]
Hematocrit (HCT) 42.4 % [38.0-50.0]
MCV 94 FL** [80-99]
MCH 32.1 Pg** [27.0-34.0]
MCHC 34.0 % [32.0-35.5]
RDW 13.1 % [11.0-15.0]
Platelet count 271 K/mL ** [140-390]

* The reference ranges are age- and sex-dependent. In adults, the reference ranges for
RBC count, HGB and HCT are higher in males than females.
** pg: picogram; 1pg=1.0-12 gram; FL: femtoliter; 1.0-15 liter; K/mL: thousand/microliter
RBC and platelet count
 WBC Differential

Flow technology which measures cell size and nuclear/cytoplasmic complexity

 CBC
• WBC count (k/mL)

• RBC count (M/mL)

• Hemoglobin (g/dL)

• MCV (mean corpuscular volume; fL):

• HCT (Hematocrit; %):

• MCH (mean corpuscular Hb; pg)

• MCHC (mean corpuscular Hb concentration; %):

• RDW (red cell distribution width; %)

• Platelet count
 RBC indices
• RBC count (M/mL)

• Hemoglobin (g/dL)

• MCV (mean corpuscular volume; fL):

– “How big is the RBC?” (average red cell volume)

• HCT (Hematocrit; %):

– “What is the percent of total blood volume occupied by RBCs?”

• MCH (mean corpuscular Hb; pg)

– “How much hemoglobin in a RBC?”

• MCHC (mean corpuscular Hb concentration; %):

– “What is the concentration of hemoglobin in red cells?”

• RDW (red cell distribution width; %):

– “What is the degree of size variation in RBCs?”
 CBC: RBC count
• Direct counting of the number Interference:
of “particles” within certain Falsely high RBC count:

size ranges in a whole blood – Marked leukocytosis (>100 K/UL);

– Giant platelets
sample by an automated
instrument.
Falsely low RBC count:
– RBC agglutination (cold agglutinin);

• RBC and WBC are counted – Microcytosis

together

(The 500 times excess of RBCs over

WBCs makes the error caused by
inclusion of WBCs in RBC count
insignificant).
Marked leukocytosis Giant platelets
 CBC: Hemoglobin
• Hemoglobin (g/dL): • The hemoglobin in the right
– RBC lysed and measured tube will be:
spectrophotometrically (light A. Falsely low
absorbance) B. Falsely high

C. Not affected
• Interference D. I don’t know
– Falsely high Hb: increased
sample turbidity

Hyperlipidemia

Hyperbilirubinemia

High protein

Marked leukocytosis
 CBC
• WBC count (k/mL)

• RBC count (M/mL) - measured

• Hemoglobin (g/dL) - measured

• HCT (Hematocrit; %): calculated (automated counters)

• MCV (mean corpuscular volume; fL): measured

• MCH (mean corpuscular Hb; pg): calculated

• MCHC (mean corpuscular Hb concentration, g/dL): calculated

• RDW (red cell distribution width): measured

• Platelet count
 CBC: Hematocrit (HCT)

HCT (%): calculated using red Interference

count and MCV
RBC volume/total blood volume x100
“What is the percent of total blood
volume occupied by RBCs?”
Falsely high HCT
– Marked leukocytosis;
– Hyperglycemia (osmotic effect)
Falsely low HCT:
– RBC agglutination

– Microcytosis

50%

HCT
50%

Leukocytosis RBC agglutination

 CBC: MCV (Mean corpuscular volume)

MCV (fL): Interference

Average red cell volume; “How big is
the RBC?”
– Low MCV: microcytosis
(e.g. iron deficiency anemia)
– High MCV: macrocytosis
(e.g. B12 deficiency)
Falsely high MCV:
– Red cell agglutination;
– Osmotic abnormalities
(hyperglycemia, hypernatremia)
– Significantly increased young
RBCs (larger than old RBC).

Macrocytic RBC Normocytic RBC Microcytic RBC

Color Atlas of Hematology, CAP
 CBC
• WBC count (k/mL)

• RBC count (M/mL)

• Hemoglobin (g/dL)

• HCT (Hematocrit; %):

• MCV (mean corpuscular volume; fL):

• MCH (mean corpuscular Hb; pg)

• MCHC (mean corpuscular Hb concentration, g/dL):

• RDW (red cell distribution width)

• Platelet count
 MCH (Mean corpuscular hemoglobin)
MCHC (Mean corpuscular hemoglobin concentration)

MCH: Hb/RBC count Example: RBCs of a patient with iron

deficiency anemia are often microcytic &
The average hemoglobin content in a
hypochromic.
RBC cell; “How much Hb in a RBC?”

MCHC: Hb/Hct
Hemoglobin concentration (%) in RBC
cells; “What is the concentration of Hb in
RBCs?”

Low MCH/MCHC: Hypochromic RBC

Normocytic, normochromic Microcytic, hypochromic

 CBC
• WBC count (k/mL)

• RBC count (M/mL)

• Hemoglobin (g/dL)

• HCT (Hematocrit; %):

• MCV (mean corpuscular volume; fL):

• MCH (mean corpuscular Hb; pg)

• MCHC (mean corpuscular Hb concentration, g/dL):

• RDW (red cell distribution width)

• Platelet count
 CBC: RDW (red cell distribution width)

• The degree of variation of RBC volume/size

– Higher RDW correlates with higher degree of volume/size variation in RBC

RDW-CV: Red cell distribution width-coefficient variation

RDW-SD: Red cell distribution width-standard deviation

• Hematopathology terminology
– Anisocytosis: RBC variation in size

– Poikilocytosis: RBC variation in shape

– Anisopoikilocytosis: RBC variation in both size and shape

 “Rule of three”
• A 42 year-old female with no
significant past medical history
came for annual physical.

Test Results Reference

WBC 5.0 3.5-10.5
Red cell count 4.03 3.80-5.20
Hemoglobin 12.7 11.6-15.4
Hematocrit 37.7 34.0-45.0
MCV 90 80-99
MCH 31.5 27.0-34.0
MCHC 33.7 32.0-35.5
RDW 12.5 11.0-15.0
Platelet 223 140-390

RBC count x 3 = Hemoglobin

Hemoglobin x 3 = Hematocrit
(Normal)
 “Rule of three”
• A 42 year-old female with no • A 30 year-old healthy female with
significant past medical history microcytosis. Iron studies were
came for annual physical. normal.

Test Results Reference Test Results Reference

WBC 5.0 3.5-10.5 WBC 6.4 3.5-10.5
Red cell count 4.03 3.80-5.20 Red cell count 5.90 H 3.80-5.20
Hemoglobin 12.7 11.6-15.4 Hemoglobin 13.0 11.6-15.4
Hematocrit 37.7 34.0-45.0 Hematocrit 34.1 34.0-45.0
MCV 90 80-99 MCV 59 L 80-99
MCH 31.5 27.0-34.0 MCH 29.1 27.0-34.0
MCHC 33.7 32.0-35.5 MCHC 32.3 32.0-35.5
RDW 12.5 11.0-15.0 RDW 15.0 11.0-15.0
Platelet 223 140-390 Platelet 250 140-390

RBC count x 3 = Hemoglobin RBC count >> Hemoglobin; low MCV

Hemoglobin x 3 = Hematocrit (Highly suggestive of thalassemia)
(Normal)
 CBC
• WBC count (k/mL)

• RBC count (M/mL)

• Hemoglobin (g/dL)

• HCT (Hematocrit; %):

• MCV (mean corpuscular volume; fL):

• MCH (mean corpuscular Hb; pg)

• MCHC (mean corpuscular Hb concentration, g/dL):

• RDW (red cell distribution width)

• Platelet count
 CBC: Platelet count
• Direct counting of the number of
“particles” within certain size
ranges in a whole blood sample by
an automated instrument.

Micro clot Platelet clumping

• Falsely low platelet count:
– Clotted sample (platelets trapped in
the blood clots)

– Platelet clumping (cannot be

counted as individual platelet)

– Frequent giant platelets (giant

platelets may be counted as WBC or
Platelet satellitosis Giant platelets
RBC because of their large size)
 Summary of CBC interference
Parameters Falsely high Falsely low
RBC count Marked leukocytosis RBC agglutination
Rouleaux formation
Marked microcytosis
Hemoglobin Increased plasma turbidity: Diluted specimen
- Hyperlipidemia
- Hyperbilirubinemia
- High protein
- Marked leukocytosis
Hematocrit Marked leukocytosis RBC agglutination
(HCT) Marked hyperglycemia Microcytosis

MCV RBC agglutination

Hyperglycemia
Significant number of young RBCs

Platelet Marked red cell fragmentation Clotted sample

Platelet clumping
Platelet satellitosis
Red blood cell morphology
Peripheral blood smear
 Normal peripheral blood smear

Neutrophil Lymphocyte Monocyte Eosinophil Basophil

 Morphologic Evaluation of RBC

• Distribution
• Size
• Color
• Shape
• Inclusions
 RBC distribution: Rouleaux

Rouleaux: RBC arranged like a “stack of coins” due to

increased plasma protein

Associated clinical conditions

- Multiple myeloma (a plasma cell malignancy)
- Some lymphomas
- Chronic Inflammation; chronic infection
- Others

Color Atlas of Hematology, CAP

 RBC distribution: Agglutination

RBC agglutination: RBC cluster or clump together in an irregular mass

Associated clinical conditions

- Cold agglutinin autoimmune hemolysis
(Antibodies, usually IgM, against RBC)

Color Atlas of Hematology, CAP

 Morphologic Evaluation of RBC

• Distribution
• Size
• Color
• Shape
• Inclusions
 RBC Size and Color

Normocytic, normochromic RBC Microcytic, hypochromic RBC Macrocytic RBC

Central pallor > 1/3

of RBC diameter

Color Atlas of Hematology, CAP

 Polychromatophilic cells
(Young RBC in blood)

Polychromatophilic cells: young RBC; larger than mature RBC, with bluish tinge
due to higher RNA content than mature RBC.

Reticulocyte: polychromatophilic cells stained with supravital stain.

The network of dark blue granular materials within the cells represent
precipitated RNA and other organelles

Reticulocyte count reflects RBC production in bone marrow

 Morphologic Evaluation of RBC

• Distribution
• Size
• Color
• Shape
• Inclusions
 RBC Shape – Elliptocyte (ovalocytes)

Color Atlas of Hematology, CAP

Associated clinical conditions:

- Hereditary elliptocytosis
- Iron deficiency anemia - microcytic, Megaloblastic anemia
(B12/folate) - macrocytic
- Others
 RBC Shape – Echinocytes (burr cells)

Color Atlas of Hematology, CAP

Echinocyte (burr cell): symmetric short, sharp projections

Associated clinical conditions:

- Chronic renal disease
- Hyperlipidemia
- Others
 RBC Shape – Acanthocyte (spur cell)

Acanthocyte: asymmetric, unequal long projections Color Atlas of Hematology, CAP

Associated clinical conditions:

- Severe liver disease
- Abetalipoproteinemia
- Others
 RBC Shape – Target cell

Target cells

Associated clinical conditions

- Chronic liver disease
- Hemoglobinopathy (e.g. thalassemia, hemoglobin C)
- Others
 RBC Shape – Teardrop cells

Teardrop RBC Color Atlas of Hematology, CAP

Associated clinical conditions:

- Bone marrow fibrosis (myelofibrosis)
- Infiltration (e.g. carcinoma) in marrow
- Others
 RBC Shape – Sickle cell

Sickle cell: Curved RBC with sharp ends

Associated clinical conditions:

- Sickle cell disease (HB S/S)

Color Atlas of Hematology, CAP

 RBC Shape-Spherocytes

Spherocytes: Dark red RBC with no central pallor

Associated clinical conditions:

Color Atlas of Hematology, CAP
- Hereditary spherocytosis
- Immune hemolytic anemia
- Others
 RBC Shape – Bite cell

Heinz body (supravital stain)

Associated clinical conditions:

Heinz body hemolysis
- G-6-PD deficiency
- Unstable hemoglobin
- Oxidant drugs

Color Atlas of Hematology, CAP

 RBC Shape – Schistocyte

Color Atlas of Hematology, CAP

Schistocytes: Red cell fragments

Associated clinical conditions:

- Microangiopathic hemolysis (MAHA)
- Artificial heart valve
 RBC morphology associated with hemolysis

Spherocytes: Schistocytes Bite cells

(Immune hemolysis) (Microangiopathic hemolysis) (Heinz body hemolysis)
(e.g. G-6-PD deficiency)
RBC morphology and associated clinical conditions
(Summary)

Hypochromic cell: central pallor >1/3 of the RBC (pale red cell)
Conditions: iron deficiency anemia; thalassemia; others

Ovalocyte (elliptocyte): oval red cells

Conditions: hereditary elliptocytosis; B12/folate deficiency; iron deficiency; others

Target cell
Conditions: liver disease; hemoglobinopathy (e.g. thalassemia, hemoglobin C);
others

Burr cell: symmetric short, blunt projections

Conditions: kidney disease (acute renal failure); others

Acanthocyte: asymmetric, unequal long projections

Conditions: chronic liver disease; abetalipoproteinemia; others
RBC morphology and associated clinical conditions
(Summary)
Teardrop cell
Conditions: myelofibrosis; bone marrow infiltrate (e.g. carcinoma); iron deficiency

Spherocyte: dark RBC with no central pallor

Conditions: hereditary spherocytosis; immune-mediated hemolytic anemia; others

Bite cell: one or more “bites” in RBC

Conditions: Heinz body hemolysis (G-6PD deficiency; unstable hemoglobins; oxidant drugs)

Schistocyte: irregularly shaped RBC fragments

Conditions: microangiopathic hemolytic anemia, such as DIC (disseminated
intravascular coagulation), HUS (hemolytic uremic syndrome), and TTP (thrombotic
thrombocytopenic purpura); artificial cardiac valves

Sickle cell: curved RBC with sharp ends

Conditions: sickle cell disease (Hb S/S)
 CBC
• WBC count (k/mL)

• RBC count (M/mL)

• Hemoglobin (g/dL)

• MCV (mean corpuscular volume; fL):

• HCT (Hematocrit; %):

• MCH (mean corpuscular Hb; pg)

• MCHC (mean corpuscular Hb concentration, g/dL):

• RDW (red cell distribution width)

• Platelet count
 Morphologic Evaluation of RBC

• Distribution
• Size
• Color
• Shape
• Inclusions
 Question 1
A 20 year-old female with history of
1. How do you describe the RBCs?
heavy menstrual bleeding came to
clinic for fatigue and dizziness.
CBC showed the following:
2. The most likely diagnosis is:
Test Results Reference
WBC 5.4 3.5-10.5
A. Hemolysis
Red cell count 2.5 3.80-5.20 B. Iron deficiency anemia
Hemoglobin 7.0 L 11.6-15.4
C. Thalassemia
Hematocrit 22.0 L 34.0-45.0
MCV 66 L 80-99
D. B12 deficiency
MCH 20.1 L 27.0-34.0
MCHC 27.0 L 32.0-35.5
RDW 21.0 H 11.0-15.0
Platelet 380 140-390
 Question 1
A 20 year-old female with history of
1. How do you describe the RBCs?
heavy menstrual bleeding came to
Microcytic, hypochromic RBC
clinic for fatigue and dizziness.
CBC showed the following:
2. The most likely diagnosis is:
Test Results Reference
WBC 5.4 3.5-10.5
A. Hemolysis
Red cell count 2.5 3.80-5.20 B. Iron deficiency anemia
Hemoglobin 7.0 L 11.6-15.4
C. Thalassemia
Hematocrit 22.0 L 34.0-45.0
MCV 66 L 80-99
D. B12 deficiency
MCH 20.1 L 27.0-34.0
MCHC 27.0 L 32.0-35.5
RDW 21.0 H 11.0-15.0
Platelet 380 140-390
 Question 2
A 19 year-old female with no past
medical history was found to have What’s your interpretation of the

an abnormal CBC in a routine CBC results?

check-up. A.Iron deficiency anemia

Test Results Reference B.Unremarkable
WBC 5.4 3.5-10.5
C.Possible thalassemia
Red cell count 5.80 H 3.80-5.20
Hemoglobin 12.0 11.6-15.4 D.I have no idea
Hematocrit 34.1 34.0-45.0
MCV 60 L 80-99
MCH 29.1 27.0-34.0
MCHC 32.3 32.0-35.5
RDW 15.0 11.0-15.0
Platelet 250 140-390
 Question 2
A 19 year-old female with no past
medical history was found to have What’s your interpretation of the

an abnormal CBC in a routine CBC results?

check-up. A.Iron deficiency anemia

Test Results Reference B.Unremarkable
WBC 5.4 3.5-10.5
C.Possible thalassemia
Red cell count 5.80 H 3.80-5.20
Hemoglobin 12.0 11.6-15.4 D.I have no idea
Hematocrit 34.1 34.0-45.0
MCV 60 L 80-99
MCH 29.1 27.0-34.0
MCHC 32.3 32.0-35.5
RDW 15.0 11.0-15.0
Platelet 250 140-390
Question 3

This is a peripheral blood smear

from a newborn girl who has
jaundice and increased bilirubin.
The possible cause is:

A. Immune hemolysis
B. Microangiopathic hemolysis
C. G-6-PD deficiency
D. All of the above
Question 3

This is a peripheral blood smear

from a newborn girl who has
jaundice and increased bilirubin.
The possible cause is:

A. Immune hemolysis
B. Microangiopathic hemolysis
C. G-6-PD deficiency
D. All of the above
 Question 4

• Chronic liver disease

• Chronic renal disease

• Microangiopathic hemolysis

• Bone marrow fibrosis

• Immune hemolysis
 Question 4
Target cells
• Chronic liver disease

• Chronic renal disease Schistocytes

• Microangiopathic hemolysis Burr cells

• Bone marrow fibrosis Spherocyte

• Immune hemolysis
Teardrop cell
 Question 5

A 19-year-old college student What is the next step to evaluate

with no significant past medical
history was found to have low
platelet count on CBC. He has no
family history of bleeding
disorder. CBC shows: WBC 6.0
k/ml, RBC 5.0 M/mL, Hb 15 g/dL,
Hct 45 %, MCV 85 fL, RDW 13%,
Plt 30 k/ml.
this patient’s thrombocytopenia?
A.Review of peripheral blood
smear.
B.Bone marrow biopsy
C.Treat patient with steroid
D.Leave him alone
 Question 5
A 19-year-old college student
with no significant past medical
history was accidentally found to
have low platelet count on CBC.
He has no family history of
bleeding disorder. CBC shows:
WBC 6.0 k/ml, RBC 5.0 M/mL, Hb
15 g/dL, Hct 45 %, MCV 85 fL,
RDW 13%, Plt 30 k/ml.
What is the next step to evaluate
this patient’s thrombocytopenia?
A.Review of peripheral blood
smear.
B.Bone marrow biopsy
C.Treat patient with steroid
D.Leave him alone
Platelet satellitosis