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CLINICAL PATHOLOGY – CBC INTERPRETATION AND PERIPHERAL BLOOD SMEAR

Lecturer: Dr. Garcia


Date: December 10, 2018
Transcribed by: OOZMA KAPPA

INTRODUCTION
OUTLINE
1. Terms
• Haematology comprise of
2. Introduction o ‘Haima’ = blood in Greeks
3. Complete Blood Count o ‘Logos’ = study
4. Red Blood Cells • Haematology is a unique super speciality in medicine
5. Haemoglobin which encompasses the fields of pathology
6. Reticulocyte
(hematopathology), physiology, biochemistry, molecular
7. Haematocrit
8. RBC Indices biology, obstetrics and gynecology, medicine and
9. Peripheral Blood Smear pediatrics
10. White Blood Cell Count
11. Platelet Count COMPLETE BLOOD COUNT (CBC)
12. Low Blood Counts
• A complete blood count is a series of tests used to
13. High Blood Counts
evaluate the composition and concentration of the
various cellular and fluid components of the blood
Recording; old file • Is a basic test
TERMS • Most informative single investigation of blood
• Anisopoikilocytosis • Test consists of
o Variation in size and shape of the erythrocytes o Counts of RBC, WBC, Platelets
• Cytometry o Haemoglobin, haematocrit, and red cell indices
o Measurement of the cell either visual or o TLC, DLC
automated o Platelet count, mean platelet volume, platelet
• Cluster Analysis count, PDW
o Analysis that is based upon the instrument’s o Histogram of RBC, WBC, Platelets
ability to cluster different populations, together
based upon size, staining, absorption or other HOW IMPORTANCT IS CBC?
parameter • To know the importance of CBC, we need to know…
• Contour Grafting o What is CBC?
o Analysis where information is plotted three o Why to request for a CBC?
dimensionally, that can be separate o What are various parameters of CBC?
subpopulation of cells o What are variations in parameter of CBC?
o Quantitative analysis o What these variations can tell us?
• Coulter Principle (Electrical Impedance) o How these variations affect the assessment and
o Sizing and counting cells by detecting and care of patients?
measuring changes in electrical resistance when
cell passed through small aperture WHY CBC?
• Dimorphic • CBC is an inexpensive too and powerful too which
o Two population of cells in single blood sample provide information about
• Forward Angle Light Scatter o Blood (primarily), also about
o Light from laser source is scatter in forward o Marrow
direction (0 degree) when it strike a cell or o Health or disease state of other organs of body
particle, larger object more forward light scatter
• Forward High Angle Light Scatter CBC USES
o Similar to forward angle light scatter, but angle • To diagnoses
is 5 to 15 degree variation o Anemia
• Forward Low Angle Light Scatter o Haemoglobinopathies
o Similar to forward angle light scatter, but angle o Bone marrow aplasia
is 2 to 3 degree variation o Nutritional deficiencies
o Thrombocytopenia
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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

o Autoimmune conditions • Megaloblastic anemia


o Infections and Parasitemia • Iron deficiency anemia
o Malignancies, response to drug, chemotherapy • Thalassemia
etc. • Anemia of prematurity
• Anemia of chronic disorders
COMPONENTS
• WBC • RDW (RBC distribution width) Increased Destruction
• RBC • Platelets Intra – corpuscular
• Hemoglobin • Neutrophils • Hereditary spherocytosis
• Haematocrit • Lymphocytes • Sickle cell anemia
• MCV • Monocytes • Abetalipoproteinemia
• MCH • Basophils • G6PD
• MCHC • Immature granulocytes and • Pyruvate kinase deficiency
erythrocytes • PNH (paroxysmal nocturnal hemoglobinuria)
• Reticulocyte count
Extra – corpuscular
RED BLOOD CELLS • Autoimmune
• Hemolytic disease of newborn
• Mismatch transfusion
• Microangiopathic hemolytic anemia – TTP, HUS
• DIC
• Infections

INCREASED RBCs
• Polycythemia vera
• High altitude
• Chronic obstructive pulmonary disease (COPD,
emphysema, chronic bronchitis)
• Pulmonary hypertension
• RBC produced in marrow and requires • Hypoventilation syndrome
o Iron, copper, manganese, cobalt • Congestive heart failure
o Vitamins: especially B12, Folic Acid • Obstructive sleep apnea
• Regulated by ERYTHROPOIETIN, THYROID HORMONE, • Poor blood flow to the kidneys
and ANDROGENS.
• Counts depend upon age, sex (gender), altitude, exercise, HEMOGLOBIN
drug, tobacco use, etc.
• Life span: 120 days reason for blood donation every 3
months
• Clinical importance of assessment of RBC is to:
MEASURES OXYGEN CARRYING CAPACITY OF BLOOD

NORMAL VALUES
Newborn 4.1 – 6.1 million/mm3
Children 3.6 – 5.5 million/mm3
Adult (Male) 4.6 – 6.0 million/mm3 • Oxygen carrying component of blood
Adult (Female) 4.2 – 5.0 million/mm3 • Synthesize in polychromatic normoblast stage of red cell
development (review the stages of erythropoiesis)
DECREASED RBCs
Blood Loss NORMAL VALUES
• Trauma Newborn 15.5 – 24.5 g/L
• Surgery Adult (Male) 13.5 – 16.5 g/L
• GI bleeding Adult (Female) 12.0 – 15.5 g/L
• Gynaecological disturbance • Hb is higher in newborns due to physiologic changes
happening
Impaired Production
• Pure red cell aplasia
• Pernicious anemia
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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

HEMOGLOBIN ESTIMATION • SHIFT CORRECTION FACTOR: Normal reticulocyte count


Cyanmethemoglobin Method survive 3.5 days in marrow and 1 day in peripheral
• Gold standard for hb determination circulation at normal PCV. In case of variation in PCV the
• Recommended survival time is increased which is termed as shift
• 20 microL blood + diluent (potassium cyanide and correction factor.
potassium ferricyanide)
• Mixed and read in photo colorimeter. SHIFT CORRECTION FACTOR
• PHOTOCOLORIMETER: used to determine the PATIENT’S HCT MATURATION DAYS
concentration. 45 1
• Hb%= (test sample absorbance/ standard sample 35 1.5
absorbance) x concentration of standard x dilution factor 25 2
• Advantage: Hemoglobin, methemoglobin, 15 2.5
carboxyhemoglobin are used in measurement.
• Disadvantage: Sulfmethemoglobin cannot be included in Increased Reticulocyte Count
measurement, takes more time for estimation. • Hemolytic anemia
• Recent haemorrhage
Other Methods • Thalassemia
• Sahli acid hematin • Pregnancy
• Alkaline hematin method • Response to treatment
• Sulfahemoglobin method • Hypoxia
• Oxyhemoglobin method • Leukemia

RETICULOCYTE Decreased Reticulocyte Count


• Is not normally a component of CBC result but it may • Aplastic Anemia
indicate as remarks the presence of reticulocytes • Megaloblastic Anemia
• Reticulocytes in PBS indicates reticulocytosis (over- • Anemia of Chronic disease
working bone marrow) • Cirrhosis
• NORMAL VALUE: 0.5% - 1.5% • Radiation
o Hence, 0.5% - 1.5% RBCs are replaced per day • Decrease ACTH and pituitary hormones
• Uses
o To evaluate anemia RETICULOCYTE HEMOGLOBIN MEASUREMENT (RET-He)
o Response to treatment of anemia • Reticulocyte hemoglobin is a direct assessment of the
• Note incorporation of iron into erythrocyte hemoglobin.
o If the disease causing the anemia is inside the • It is a direct estimate of the recent functional availability
marrow, the reticulocyte count is decreased of iron (2-3 days).
o If the disease causing the anemia is outside the • Traditional chemistry tests used for iron assessment
marrow, the reticulocyte count is increased (serum iron, transferrin saturation, ferritin) are indirect
measurements.
METHODS • As a direct measurement, it may identify iron deficiency
• Manual reticulocyte count using supravital stain earlier than traditional parameters.
• Automated reticulocyte count by fluorescent method • It is an established parameter used in KDOQI (Kidney
o Gives immature reticulocyte fraction (IRF) and Disease Outcome Quality Initiative) guidelines for
removes errors like Howell-Jolly bodies, and assessing iron status.
pappernheimer bodies
• Reticulocyte production index or corrected reticulocyte HEMATOCRIT
count: an index corrected according to level of anemia • Ratio of the volume of erythrocytes to that of the whole
blood in percentage.
𝑝𝑎𝑡𝑖𝑒𝑛𝑡 ′ 𝑠 ℎ𝑒𝑚𝑎𝑡𝑜𝑐𝑟𝑖𝑡
𝑹𝒆𝒕𝒊𝒄𝒖𝒍𝒐𝒄𝒚𝒕𝒆 𝒊𝒏𝒅𝒆𝒙 = 𝑟𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 𝑐𝑜𝑢𝑛𝑡 𝑥
𝑛𝑜𝑟𝑚𝑎𝑙 ℎ𝑒𝑚𝑎𝑡𝑜𝑐𝑟𝑖𝑡
• Haematocrit can be measured simply by using whole
volume of blood then centrifuge then measure the RBC
• RETICULOCYTE PROLIFERATION INDEX: Index is used to component comparing the total blood that was
determine if a person’s bone marrow is properly centrifuged
responding to the body’s need for red blood cells. • Most precise method for determining the degree of
anemia or polycythemia i.e, increase or decrease RBC
concentration.

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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

NORMAL VALUES • MCV <72 without heterogeneity, is a sensitive and


Newborn 42 – 68% specific predictor of thalassemia trait
Up to 1 year of age 29 – 41%
Adult (Male) 39 – 47% Microcytic MCV
Adult (Female) 36 – 44% Hypochromic
• Percentage unit – conventional unit • Iron deficiency
• SI – current (decimals) • Thalassemia
• Lead poisoning
• Rule of 3 • Porphyria
o RBC x 3 = Hemoglobin (Hb) Normochromic
▪ RBC x 3 ± 3= HEMOGLOBIN (Hgb) • Anemia of chronic disease
o Hb x 3 = Hematocrit (Hct) • Haemoglobinopathies

HIGH HEMATOCRIT Normocytic MCV


• Polycythemia vera • Acute haemorrhage
• Dehydration • Diamorphic anemia (small and large erythrocytes)
• Low oxygen in blood (compensatory) • Hemoglobinopathies
• Congenital heart disease • Endocrinopathies
• Cor pulmonale
• Smoking Macrocytic MCV
• Hemoconcentration (Dengue) • Megaloblastic Anemia
• Pernicious anemia
LOW HEMATOCRIT • Sprue
• Anemia • Di Guglielmo disease
• Blood loss • MDS
• Hemolysis • Post splenectomy
• Bone marrow aplasia • Alcoholism
• Leukemia • Liver disease
• Malnutrition • Drugs (anticonvulsant, anticancer, etc.)

An elevated haematocrit may be due to spleen INTERFERENCE IN MCV


hyperfunction, and reduced haematocrit may indicate low Cases wherein MCV may be falsely giving you a result
thymus function • Cold and warm antibodies
• Marked hyperglycemia
RBC INDICES • Marker leukocytosis
MEAN CORPUSCULAR VOLUME (MCV) • Marked reticulocytosis
• Measures average volume of RBC • Methanol poisoning
o MCV = haematocrit/ red cell count x 100
▪ ↓MCV just because the cells in the MEAN CORPUSCULAR HEMOGLOBIN
population are very small and large • MCH= hgb / red cell count x 100
cells
▪ ↓MCV without heterogeneity of RBC NORMAL VALUES
population is a definitive diagnosis of Newborn 36 – 38 %
thalassemia trait because in these Up to 1 year of age 23 – 27%
cases most of the RBCs in the peripheral Adult 26.7 – 31.9%
population are very very small
MCH Decreased in
NORMAL VALUES • Microcytic and normocytic anemias
Newborn 103 – 106 fL
Up to 1 year of age 78 fL MCH Increased in
Adult 79 – 98 fL • Macrocytic anemia
• Infants and newborn
• Classified accordingly as
o Microcyte – MCV <79 INTERFERENCE IN MCH
o Macrocyte – MCV >98 • Lipemia
• Presence of microcytic and macrocytic cells in same • Marked leucocytosis
sample may result in normal MCV • Cold agglutinin

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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

• Monoclonal protein in blood • In microcytes, RDW increased in iron deficiency anemia


but thalassemia it is not raised
MCH and Hb content • RDW-CV: It is the ratio of standard deviation to the mean
Hb content in a CBC result is just the Hb content of that corpuscular volume
sample volume that you’ve analysed but when you put that o RDW-CV = Standard Deviation of RBC Volume /
hb volume into a ratio over the RBC population in that same Mean MCV x 100
blood volume it gives you a more representative idea of the o Value 11.5%-14.5%
whole picture of the RBC in the body of your patient • RDW-SD: It is the actual measurement of the width of the
RBC distribution curve
It is haemoglobin in relation to the RBC’s volume. As o Value 35-45 fL
compared to MCV that compares RBC in relation to count.
RBC on PERIPHERAL BLOOD SMEAR
MEAN CORPUSCULAR HAEMOGLOBIN CONCENTRATION • The red cell characteristics are only one of the other
• MCHC = Hemoglobin / Hemotocrit x 10 components or cellular elements that are being analyzed
in a peripheral blood smear. It is a smear that is being
Normal Range read and evaluated to look for differences in morphology
Newborn 34-36% and ratio of cells. You usually check for the size and the
Upto 1 year age 31-33% degree of haemoglobin.
Adult 32-36% • Usually you have already seen your CBC report and you
want a further evaluation of some abnormalities
• MCHC decreased in detected that is why when you request for PBS you should
o Hypochromic microcytic anemia already have your CBC. Do not be surprised if the
• MCHC increased in pathologist asks for the previous CBC readings before
o Hereditary spherocytosis doing your PBS. You cannot request a PBS without
o Infants and newborns previous CBC.
o Autoagglutinations • One thing that you look for in PBS is the RBC morphology
• Interference in MCHC and the quality and characteristic of the haemoglobin
o Marked leukocytosis content of majority of the RBC seen on a smear
o Hemolysis
o Cold agglutinins PREPARATION
o Rouleaux • The wedge slide (push slide) technique was developed by
• These parameters are very important in assessing the Maxwell Wintrobe as is a standard method
response to treatment particularly in patients undergoing • The “zone of morphology” (area of optimal thickness for
blood transfusion. light microscopy) should be at least 2cm in length. The
smear should occupy the central area of the slide and be
RED CELL DISTRIBUTION WIDTH (RDW) margin free at the edges
• This is now part of the red cell indices. In the Philippines,
there are efforts being done to standardize a CBC result Microcytic Hypochromic
because if you would notice there is no actual
requirement as to what should be included in the CBC. It
just usually depends on the laboratory. Some just release
the five parameters such as haematocrit, haemoglobin,
RBC, WBC and the platelet while some release the five
parameters and the red cell indices. But theoretically, 5
parameters include haematocrit, haemoglobin, RBC, WBC
which includes the differentials meaning the total WBC
and then differentiate into the different WBC and the
platelets. But from the 5 mainstay you can already derive
your red cell indices. Clinical lab in the Philippines are • Size smaller than the nucleus of small lymphocyte
mostly automated. • < 7 micron
• Red cell distribution is a quantitative measure or • Markedly increase central pallor > 1/3 of the
numerical expression of anisocytosis. It is a coefficient of diameter of RBC
variation of distribution of individual RBC volume • Causes
• Anisocytosis – Variation in the size o Iron deficiency anemia
• RDW would give you a picture of the differences in the o Thalassemia
size of the RBC population that is being evaluated, a o Sideroblastic anemia
numerical value at least. o Anemia of chronic disease
o Haemoglobinopathies

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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

• Compare the size of RBCs to lymphocytes, if you have o Liver Disease


smaller RBC then that denotes smaller than normal o Post Splenectomy
erythrocytes or “microcytes”. It has to be majority of o Severe Iron Deficiency Anemia
the cells of at least more than 10% of the cells that o Abetalipoproteinemia
you’re looking at. You have to cover 10 fields before • Most of the target cells that doc see are commonly due to
saying that you’ve covered majority of the analysis IDA
area of the PBS
Schistocytes
Macrocytic Cells

• Size > 8.3 micron in diameter


• Causes
• “schisto” – split or cleft
o Vitamin B 12 and Folic Acid Deficiency
• Physical assault to erythrocytes with in the blood stream
o Alcoholism
creates these cells
o Liver disease
o Myelodysplastic syndrome • Which includes
o Hypothyroidism o Helmet cells
o Drug that impair DNA synthesis o Triangles
o Crescents
• Oval Macrocytes
o Microspherocytes
o Vitamin B12 and Folic Acid Deficiency
o Horns
o Pernicious Anemia
o Purse
o Myelodysplastic Syndrome
o Hypothyroidism • Causes
o Drug that impair DNA synthesis o DIC
o Severe Hemolytic Anemia
• Round Hypochromic Macrocytes
o Microangiopathic Hemolytic Anemia
o Alcoholism
o HUS and TTP
o Hypothyroidism
o Prosthetic Cardiac Valves
o Liver Disease
o Connective Tissue Disorders
o Post Splenectomy
o Burns
• Blue tinged Macrocytes
o Acute Tubular Necrosis,
o Neonate
o Glomerulonephritis
o Response to anemic stress
o Malignant Hypertension
• They should be mostly covering the whole smear. You
Target or Bell Cell
don’t just find them in one area of the smear. In case you
see those, you have to think of artifactual changes.

Tear Drop Cells (Dacrocytes)

• They have a characteristic ringed appearance. This is


because of the “increase surface area to volume ratio”
i.e. increase in red cell membrane which get pooled at
the center of cells
• Causes
o Thalassemia • Pear shape cells, usually microcytic and hypochromic
o Haemoglobinopathies Hb AC or CC, HbSS, SC
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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

• Seen in Burr Cells (Echinocytes)


o Newborn
o Thalassemia major
o Myeloproliferative disorder
o Leukoerythroblastic reaction

Spherocytes

• 10-30 spicules equal in size and evenly distributed


over RBC surface; caused by alteration in
extracellular environment
• Seen in
o Liver disease
o Renal failure
• Ball shaped red cells, decreased surface: volume ratio, o Dehydration
hyperdense (> MCHC) o Pyruvate kinase deficiency
• Seen in o Storage artefacts
o Hereditary spherocytosis • They may mistake for crenated RBC
o ABO incompatibility
o Autoimmune hemolytic anemia Spur Cells (Acanthocyte)
o Microangiopathic hemolytic anemia
o SS Disease
o Hypersplenism
o Burns
o Post Transfusion

Elliptocytes

• They are also spiculed erythrocytes but they would


have lesser spicules as compared to burr cells
• Acantho – “thorn”
• Cells with 5-10 spicules of varying length, irregular in
shape, thickness, with wide bases, and appear
• Elliptical and normochromic cells, seen normally in
smaller than normal cell because they assume
less than 1% of RBCs
spheroid shape
• Causes
• Result from changes in membrane lipid content
o Hereditary elliptocytosis
• Seen in
o Iron deficiency anemia (increased with
severity) o Spur cell anemia
o Alcoholism
o SS Disease and SA trait
o Hypothyroidism
o Thalassemia Major
o Abetalipoproteinemia
o Leukoeryhtroblastic reaction
o Vitamin E deficiency
o Malaria
o Malabsorption
o Megaloblastic anemia
o Postsplenectomy

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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

Bite Cells (Degmacyte) o Post splenectomy


o Newborns
o Megaloblastic anemia
o Dyserythropoietic anemias
o Hereditary spherocytosis

Heinz Bodies

• Appear as a cookie with a bite taken out


• Seen in G6PD
• When spleen removes the Heinz bodies from RBCs

Stomatocyte
• Inclusion of denatured hemoglobin caused by
oxidation of globin portion of haemoglobin
• Removal of Heinz body leads to formation of “bite
cells”
• Causes
o Drugs
o Certain foods like fava beans and onion
• Cell of origin of bite cells

Sideroblastic granules/Pappenheimer bodies

• When examined on dry smear, it has a central slit or


stoma
• Seen in
o Few may be seen normally
o Various cardiovascular and pulmonary
disorders
o Hereditary
o Alcoholism
o Liver disease
o Malignancies
• Irregular dark blue iron containing granules
Howell-Jolly Bodies occurring in small clusters, predominantly in
periphery
• Seen in
o Sideroblastic anemia
o Splenectomy
o Hemolytic anemia
o Myelodysplastic syndromes
o Lead Poisoning
o Its presence can rule out iron deficiency
anemia

• Small well defined, rounded, densely stained


inclusions, 1 micron in diameter, eccentric, that
represent DNA fragments
• Associated with rapid or abnormal RBC formation
• Seen in
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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

Sickle Cells o Hemoglobinopathies


o Macrocytic anemia
• Lead Poisoning: Sideroblastic granules + Basophilic
Stippling + Cabot Ring

Cabot Ring

• Crescent shape cells develop in


o People homozygous for haemoglobin S
o Heterozygous HbS and either thalassemia or
another Hb like Hb C
• These cells are prone to aggregation

Nucleated Red Cells


• These are delicate thread like inclusions, remnants
of the nuclear membranes in the RBC
• They can take any shape like purplish ring, figure of
eight, incomplete ring
• Seen in
o Pernicious anemia
o Lead poisoning
o Alcoholic jaundice
o Severe anemia
o Leukemia
• Cells have dense dark nucleus in the center of the cell
• Results from marked stimulation of the bone marrow Rouleaux formation
• Seen in
o Newborn (first 3-4 days)
o Acute bleeding severe haemolytic anemia
o Megaloblastic anemia
o Congenital infections (syphilis, CMV, rubella)
o Post splenectomy
o Leukoerythroblastic reaction
o Fungal and mycobacterial infections
o Dyselectropoietic anemia

Basophilic Stippling
• A stack like arrangement of red blood cells where the
biconcave surface of RBCs are next to each other.
• Seen in
o Increase in cathodal protein, such as
immunoglobulins and fibrinogen
o Multiple myeloma
o Macroglobulinemia
o Acute and chronic infections
o Connective tissue disease
o Diabetes mellitus
o Malignancies

• Numerous small, purplish inclusions, which results Grading of inclusions


from RNA and mitochondrial remnants Rare 0-1/hpf
• Seen in Few 1-2/hpf
o Lead toxicity Mod 2-4/hpf
o Thalassemia Many >5/hpf

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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

• Qualitative grading of abnormal RBC morphology LEUKOCYTOSIS


Grade Degree of Abnormalities • Known as leukocytosis infection, most commonly
1-5 cells /10fields Slight bacterial or viral or parasitic
6-15 cells /10 fields Moderate • Inflammation
>15 cells /10fields Marked • Leukemia, myeloproliferative disorders
Remember you need to atleast look in 10 powerfields in a • Allergies, asthma
peripheral blood smear but if you look in more than ten then • Tissue death (trauma, burns, heart attack)
that would be better. • Intensive exercise or severe stress
• Will mention in detail in respective cell line.
WHITE BLOOD CELL COUNT
• The normal number of WBCs in the blood is 4,500-11,000 Differential Counts
white blood cells per microliter (mcL). Normal value Neutrophil 50-70 %
ranges may vary slightly among different labs. Segmenter 50-65 %
Stab 0-5 %
LEUKOPENIA Eosinophil 0-3 %
• Low white cell count may be due to acute viral infections, Basophil 0-1 %
such as with a cold and influenza. It can be associated Lymphocytes 20-40%
with chemotherapy, radiation therapy, myelofibrosis, Monocytes 2-6%
and anaplastic anemia (failure of white cell, red cell and
platelet production). HIV and AIDS are also a threat to NEUTROPENIA
white cells. • Decreased production in the bone marrow due to:
o It’s one parameter that oncologist look at when o Aplastic anemia – you have decrease in all cell
they do surveillance of their patients. lineages including RBCs and WBCs
• Other causes of low WBC count include systemic lupus o Arsenic poisoning
erythematosus, Hodgkin’s lymphoma, some types of o cancer, particularly blood cancers
cancer, typhoid, malaria, tuberculosis, dengue, o certain medications
rickettsial infections, enlargement of the spleen, folate o hereditary disorders (e.g. congenital
deficiencies, psittacosis, sepsis, and Lyme disease. Many neutropenia, cyclic neutropenia)
other causes exist, such as deficiency in certain minerals, o radiation
such as copper and zinc. o Vitamin B12, folate or copper deficiency
• Increased destruction:
PSEUDOLEUKOPENIA o Autoimmune neutropenia
• Pseudoleukopenia can develop upon the onset of o Chemotherapy treatments, such as for cancer
infection. The leukocytes (predominately neutrophils, and autoimmune diseases
responding to injury first) start migrating towards the • Marginalization and sequestration:
opposite site of infection and can be scanned at the site o Hemodialysis
of infection. Their migration causes bone marrow to • Medications
produce more WBCs to combat infection as well as to o Flecainide (a class 1C Cardiac antiaarhythmic
restore the leukocytes in circulation, but as the blood drug)
sample is taken upon the onset of infection, it contains o Phenytoin
low amount of WBCs, which is why it is called o Indomethacin
“pseudoleukopenia’. o Propylthiouracil
• False decrease in WBC count o Carbimazole
o Chlorpromazine
Drugs Causing Leukopenia o Trimethoprim/Sulfamethoxazole
• LOADS!!! (cotrimoxazole)
• Clozapine, buproprion, valproic acid, minocycline, o Clozapine
lamotrigine o Ticlodipine
• Immunosuppressive drugs, such as sirolimus, • Often, a mild neutropenia is seen in viral infections.
mycophenolate, mofetil, tacrolimus, cyclosporine, Additionally, a condition called morning
Leflunomide (Arava) and TNF inhibitors. Interferons pseudoneutropenia might be a side effect of certain
used to treat multiple sclerosis, such as Rebif, Avonex, antipsychotic medications.
and Betaseron, can also cause leukopenia.
• Chemotherapeutic drugs NEUTROPHILIA
• Lots of others • Acute or chronic infection – primarily those cause by
bacteria.
• Myeloproliferative disorders
• Acute stress
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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

• Leukemoid reactions • Some cancers, leukemias or lymphomas


• Drugs (steroids)
• Chronic inflammation BASOPENIA
• Tumors • As with eosinophils, numbers are normally low in the
• Myelophthisis blood usually not medically significant
• Hyperactive marrow
• Post splenectomy BASOPHILIA
• Cigarette smoking • Rare, allergic reactions (hives, food allergy)
• Hypoxia • Inflammation (rheumatoid arthritis, ulcerative colitis)
• Epinephrine • Some leukemias
• Exercise
PLATELET COUNT
LYMPHOCYTOPENIA • Normal platelet counts are in the range of 150,000 to
• Autoimmune disorders (e.g. lupus, rheumatic arthritis) 400,000per microliter (or 150 – 400 x 109 per liter), but
• Infections (e.g. HIV, viral hepatitis, typhoid fever, the normal range for the platelet count varies slightly
influenza) among different laboratories
o In viral infections there is a decrease in
lymphocytes initially. THROMBOCYTOPENIA
• Bone marrow damage (e.g. chemotherapy, radiation • Immune Thrombocytopenia (ITP)- formerly known as
therapy) immune thrombocytopenia purpura and idiopathic
• Corticosteroids thrombocytopenic purpura
• Cirrhosis
LYMPHOCYTOSIS • Splenomegaly
• Acute viral infections (e.g., Chicken pox, cytomegalovirus o Gaucher’s disease
(CMV), Epstein-Barr virus (EBV), herpes, rubella) • Familial Thrombocytopenia
• Certain bacterial infections (e.g. pertussis, whooping • Chemotherapy, radiotherapy
cough, tuberculosis (TB)) – peculiar increase in • Babesiosis, dengue, Onyalai, Rocky mountain spotted
lymphocytes fever
• Toxoplasmosis • Thrombotic Thrombocytopenic Purpura
• Chronic inflammatory disorder (e.g. ulcerative colitis) • HELLP Syndrome
• Lymphocytic leukemia, lymphoma, • Hemolytic Uremic Syndrome
• Stress (Acute) • Drug induced thrombocytopenia (Heparin Induced
Thrombocytopenia, acetaminophen, quinidine, sulfa
LOW MONOCYTES drugs)
• Usually, one low count is not medically significant. • Pregnancy associated
Repeated low counts can indicate: • Neonatal autoimmune associated
o Bone marrow damage or failure • Aplastic anemia, leukemia, lymphoma
o Hairy Cell Leukemia • Transfusion associated

MONOCYTOSIS THROMBOCYTOSIS
• Chronic infections (e.g., TB, fungal infections) • Reactive
• Infection within the heart (bacterial endocarditis) o Chronic infection
• Collagen vascular diseases (e.g., lupus, scleroderma, o Chronic inflammation
rheumatoid arthritis, vasculitis) o Malignancy
• Monocytic or myelomonocytic leukemia (acute or o Hyposplenism (post splenectomy)
chronic) o Iron deficiency
o Acute blood loss
LOW EOSINOPHILS • Myeloproliferative disorders – platelets are both
• Numbers are normally low in the blood. One or an elevated and activated
occasional low number is usually not medically significant o Essential thrombocytosis
o Polycythemia vera
EOSINOPHILIA • Associated with other myeloid neoplasms
• Asthma, allergies such as hay fever • Congenital
• Drug reactions • Cancer (lung, gastrointestinal, breast, ovarian,
• Parasitic infections lymphoma)
• Inflammatory disorders (celiac disease, inflammatory • Kawasaki disease
bowel disease) • Soft tissue sarcoma

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CLINICAL PATHOLOGY – CBC Interpretation and Peripheral Blood Smear

• Osteosarcoma
• Dermatitis (rarely)
• Inflammatory bowel disease
• Rheumatoid arthritis
• Nephritis
• Nephrotic Syndrome
• Bacterial diseases, including pneumonia, sepsis,
meningitis, urinary tract infections, and septic arthritis.

MEAN PLATELET VALUE


• Typical range of platelet volumes is 9.7 – 12.8 fL
• Low value indicates average size of platelets is small;
older platelets are generally smaller than younger ones
and a low MPV may mean that a condition is affecting
the production of platelets by the bone marrow.
• High volume indicates a high number of larger. Younger
platelets in the blood; this may be due to the bone
marrow
• High volume indicates a high number of larger, younger
platelets in the blood; this may be due to the bone
marrow producing and releasing platelets rapidly into the
circulation.

PLATELET DISTRIBUTION WIDTH


• A high PDW means increased variation in the size of the
platelets, which may mean that a condition is present
that is affecting platelets.

LOW BLOOD COUNTS


• All three lines (RBC, WBC, platelets) depressed in
o Aplastic Anemia
o Myelodysplastic syndrome
o Chemotherapy

HIGH BLOOD COUNTS


• Polycythemia Vera (secondary)

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