COMPLETE

BLOOD COUNT

ABDELLATIF ALY
MOHAMED
CBC COMPONENTS

• Red Blood Cells (RBCs)

• Hematocrit (Hct)
• Hemoglobin (Hgb)
• Mean Corpuscular Volume (MCV)
• Mean Corpuscular Hemoglobin(MCH)
• Mean Corpuscular Hemoglobin Concentration (MCHC)
• Red cell distribution width (RDW)
• White Blood Cells (WBCs)
• Platelets
• Mean Platelet Volume (MPV)
PRODUCTION OF ERYTHROCYTES: ERYTHROPOIESIS
ERYTHROPOIESIS

1. The process of formation of RBCs is called Erythropoiesis.

2. The number of RBCs remains constant and reflects a balance between RBC production and
destruction.
3. Erythropoiesis is stimulated by erythropoietin (EPO) hormone produced by the kidney in response to
hypoxia (low oxygen in the blood). Hypoxia may be caused by:

4. – Low RBC count (Anaemia)

5. – Hemorrhage
6. – High altitude
7. – Prolong heart failure
8. – Lung disease
 Maturation Times
• Erythroblasts actively synthesize Hb. They are
categorized on the basis of total size, the amount of
Hb present, and the size of nucleus.

• RBC development is characterized by:

– A decrease in cell size

– A disappearance of nucleus
– An appearance of hemoglobin
The Complete Blood Cell Count (CBC)
Part 2
WBC Differential Count & Morphology
 WBC DISTRIBUTION & MORPHOLOGY
Evaluation of the distribution and morphology of white blood cells is one of the most valuable
procedures used in examination of the blood. The information obtained may furnish the
diagnosis, serve as a guide to therapy and as an indicator of harmful effects of radiotherapy
and chemotherapy.

In normal peripheral blood, there are three basic types of leukocytes .

1. granulocytes: which entails;
A. Neutrophils
B. Eosinophils
C. Basophils

2. Lymphocytes
3. Monocytes
• An abnormal number and/or distribution of leukocytes (WBC) may be seen in disease.
Immature WBC and/or WBC with abnormal alterations may also be seen. The immature
and abnormal cells are distinguishable from normal cells by their morphologic
characteristics.

• Recognition and identification of these abnormalities play a major role in the diagnosis
and treatment of true blood diseases and numerous other pathologic processes.

• Because the total WBC count does not differentiate WBCs as to cell lines, a differential
WBC count (“diff”) is performed to provide information regarding the frequency
distribution of WBCs and to identify increases or decreases
• when they occur in one or more of the cell lines. A morphologic study of the various
blood cells (i.e., WBC, RBC, & platelets) is made during the differentiation process to
detect and identify atypical and/or abnormal cells.
 Typical nuclear and cytoplasmic morphologic features provide a means by
which WBC can be identified and classified as to:

• Cell line (i.e., granulocytes [neutrophils, eosinophils, or basophils],

lymphocytes, or monocytes)
HOW ARE THE • Maturity (i.e., mature cell or specific immature stage of development).

WBC IDENTIFIED • Abnormal morphology (i.e., nuclear or cytoplasmic alterations)

AND
CLASSIFIED?
HOW ARE THE WBC DIFFERENTIATED AND ENUMERATED?
At least 100 WBC are counted, and a tabulation is made as to the number of each leukocytic cell type included in the
count.
The 100-cell count provides the RELATIVE number (or percent) of each white blood cell type present in the peripheral
blood.

HOW CAN YOU DETERMINE WHETHER THERE IS AN INCREASE OR DECREASE OF ONE OR MORE
OF THE CELL LINES?
Increases or decreases in a white blood cell line (or type) can then be determined by comparing the number obtained on
the differential count with established reference ranges.

WHAT IS THE REFRENCE RANGE?

Reference ranges (values considered to be normal) for differential WBC counts may vary among laboratories, but are
usually about:
Segmented
Lymphocytes
neutrophils
20-40%
50-70%
Band Eosinophils Monocytes
neutrophils 1-5% 1-6%
0- 5%
The total WBC count reference range for adults is 4,500- 11,000/mL, but may vary slightly among laboratories:

To remember the different types of leukocytes in their descending proportion in a blood specimen, use this mnemonic:

Never (neutrophils)
Let (lymphocytes)
Monkeys (monocytes)
Eat (eosinophils)
Bananas (basophils)
WHAT TERMINOLOGY IS USED TO INDICATE AN INCREASED OR DECREASED NUMBER OF
A SPECIFIC WHITE BLOOD CELL LINE?

Cell Line Increased Decreased

Neutrophils Neutrophilia Neutropenia
Lymphocytes Lymphocytosis Lymphocytopenia
Monocytes Monocytosis Monocytopenia
Eosinophils Eosinophilia Eosinopenia
Basophils Basophilia Basopenia
HOW DOES THE DIFFERENTIAL WBC COUNT DIFFER FROM THE TOTAL WBC COUNT?
The total WBC count reflects the total number of all leukocytes in circulation but does not differentiate leukocytes as to
their various cell lines (e.g., neutrophils, lymphocytes), stage of maturity, (e.g., band, metamyelocyte), or abnormalities
when present (e.g., toxic granulation, hypersegmented nuclei).
A differential WBC count must be performed to provide that information.

Total WBC count Differential WBC count

WHAT IS MEANT BY THE RELATIVE % AND ABSOLUTE NUMBER OF WBC ?
Relative % is based on the differential count of 100 white blood cells and reflects the per cent of each cell type present in
circulation.
If the total number of white cells in circulating blood is known and the relative per cent of each white cell type is known,
then the absolute number of each cell type per mL of blood can be calculated.
For example: given a patient with a total WBC count of 8,000/mL and the differential WBC count shown below
(i.e., the number observed for each cell type in the 100 white cell count), Then the absolute number of each cell
type/mL can be calculated by multiplying the per cent of each cell type by the total number of WBC/mL

• Segmented neutrophils 60% x 8,000 = 4,800

• Band neutrophils 5% x 8,000 = 400
• Lymphocytes 30% x 8,000 = 2,400
• Monocytes 2% x 8,000 = 160
• Eosinophils 2% x 8,000 = 160
• Basophils 1% x 8,000 = 80
DO THE RELATIVE VALUES ALWAYS INDICATE WHICH CELL LINE IS INCREASED OR DECREASED ?

If the total WBC count is “normal” (i.e., within the established reference range), the
relative values are a good reflection of the number of each cell type present, including
increases or decreases.

However, if the total WBC count is abnormal (i.e., increased or decreased), the relative
percentage must be converted to an absolute number of each cell type present in order to
determine which cell line is involved.
Given a patient whose total WBC is 8,000/mL, and the relative distribution of leukocytes on the peripheral blood
smear is as shown below:

How are the absolute numbers determined?

In this case, did the relative per cents reflect the absolute numbers ?

The answer is YES .WHY?

BECAUSE the total WBC count was within the reference range.
Therefore, because both the total and relative frequencies are within reference ranges, the relative % is a reflection of the
absolute numbers in terms of normal or abnormal.
However, given a patient whose total WBC is 15,000/mL, with a relative distribution of leukocytes on the
peripheral blood smear the same as the previous patient:

Is the interpretation the same for both patients?

DO THE RELATIVE AND ABSOLUTE VALUES HAVE THE SAME INTERPRETATION IN THIS CASE?

The relative percentages for all cell types for this patient were within the
reference range (i.e., normal).
However, in this case, there is neutrophila when converted to absolute
numbers based on a total WBC count of 15,000/mL because:

 segmented (mature) neutrophils = 9,750/mL which exceeds the reference

range (1800 - 8000/mL)
 band neutrophils = 750/mL which also exceeds the reference range
(0 - 550/mL).
Given a patient whose total WBC is 15,000/mL, with a relative distribution of leukocytes on the peripheral blood
smear the same as the previous patient:

How are these data interpreted?

 NEUTROPHILS
• Primary cell in immune response to pyogenic organisms and predominate cell in acute inflammatory infiltrates.
• Are the most common, making up about 50% to 60% of the total WBCs..
• Their life span is 4 days.
• An immature neutrophil is called a band; bands are increased in number by bacterial infection (referred to by many
clinicians as a “left shift”).

Absolute neutrophil count: The real number of white blood cells (WBCs) that are neutrophils.

The ANC is not measured directly. It is derived by multiplying the WBC count times the percent of neutrophils in the
differential WBC count. The percent of neutrophils consists of the segmented (fully mature) neutrophils) + the bands
(almost mature neutrophils). The normal range for the ANC = 1.5 to 8.0 (1,500 to 8,000/mm3).

Sample calculation of the ANC:

WBC count: 6,000 cells/mm3 of blood
Segs: 30% of the WBCs
Bands: 3% of the WBCs
Neutrophils (segs + bands): 33% of the WBCs
ANC: 33% X 6,000 = 2,000/mm3
ANC of 2,000/mm3, by convention = 2.0
Normal range: 1.5 to 8.0 (1,500 to 8,000/mm3)
Interpretation: Normal
 Neutropenia
•Defined as an absolute neutrophil count (ANC) <1500/μL
•Typically referred to as:

1. •Mild: ANC 1000-1500

2. •Moderate: ANC 500-1000
3. •Severe: ANC <500
4. Agranulocytosis: <200
• Neutropenia is potentially associated with life threatening infection. It is most significant when the total neutrophil
count is less than 0.5 x 109/L, particularly when the neutropenia is due to impaired production (e.g. after
chemotherapy). When the neutropenia is due to increased peripheral destruction or margination (e.g. with viral
infection), it is less certain what constitutes a significant level. These patients rarely have problems with significant
bacterial infection despite quite low neutrophil counts.

Red flags

1. Person particularly unwell

2. Severity of neutropenia
3. Rate of change of neutropenia
4. Lymphadenopathy, hepatosplenomegaly
 Common Causes of Neutropenia

1. Isolated neutropenia can be seen in connective tissue disorders, particularly rheumatoid arthritis and Sjogren’s
disease.
2. It can be a result of drug therapy, e.g. clozapine, azathioprine, carbimazole, such that patients need careful regular
monitoring when treated with these agents.
3. It may be seen following cytotoxic chemotherapy.
4. It is commonly seen following viral infection e.g. Epstein-Barr virus infection, when it tends to be mild and self-
limiting.
5. A sudden onset neutropenia can be seen in patients with overwhelming bacterial infection and appears to be a poor
prognostic sign.
6. Mild chronic neutropenias not associated with infection are reasonably common and are sometimes referred to as
benign idiopathic neutropenia.
7. Ethnic: Afro-Caribbean patients commonly show mild neutropenia below the normal range seen in Caucasians: this
racial neutropenia should be recognized as such and not generate unnecessary investigations.

N.B A significant persisting neutropenia requires the opinion of a haematologist particularly in patients with
cytopenias in other lineages.
 DIAGNOSIS

1. The history and clinical features are important for providing the clues for diagnosis and
allowing the results to be interpreted in context.
2. History: frequency and severity of infections, mouth ulcers, recent viral illness, exposure
to drugs and toxins, symptoms of malabsorption, symptoms suggesting reduced immunity
3. Drugs .
4. Examination: mouth ulcers, fever, signs of infection, jaundice, lymphadenopathy,
hepatomegaly, splenomegaly, signs of autoimmune/connective tissue disorders
5. CBC: is the CBC otherwise normal (particularly haemoglobin and platelets)
6. In persistent moderate neutropenia, without an infection or drug related cause, testing
might include ANA (anti-nuclear antibodies), B12, folate, SPE (serum protein
electrophoresis), HIV, liver enzymes, Hepatitis B and rheumatoid factor. Look for changes
on physical examination.
DRUGS
COMMONLY
IMPLICATED
IN
NEUTROPENIA
 Approach to patients with neutropenia

• Neutrophils <1.0 x 109/L

The risk of significant bacterial infection rises as the neutrophil count drops below 1.0 x 10 9/L, but is most marked
as the count falls below 0.5 x 109/L. Careful assessment of the patient’s condition is critical, and patients who are
unwell and/or febrile with a count below 1.0 x 109/L generally need urgent referral. Patients who are febrile but
otherwise well should at least be discussed with a Haematologist. If the patient is well and afebrile, they need to be
advised to seek medical attention promptly if their condition deteriorates or they become febrile. Well patients
should have follow up blood counts within 48 hours, and if the neutropenia persists at this level or progresses they
should be discussed with a Haematologist.
• Neutrophils 1.0 - 2.0 x 109/L
If an isolated abnormality follow up blood counts are indicated, with frequency dependent on the severity of the
neutropenia but usually within 1-2 weeks. If the neutropenia persists for more than 6 weeks further investigation is
indicated. If it is progressive or other abnormalities develop a haematology referral, or discussion with a
Haematologist, is indicated.
• Drug induced neutropenias
There are specific protocols for management of clozapine induced neutropenia. Otherwise, if a drug cause is
suspected and the neutropenia is moderate or severe, Haematology referral, or discussion with a Haematologist is
indicated.
NEUTROPHILIA (HIGH NEUTROPHIL COUNT)
Neutrophils are the primary white blood cells that respond to a bacterial infection. The most common cause of marked
neutrophilia is a bacterial infection.

Neutrophils react within an hour of tissue injury and are the hallmark of acute inflammation. An excessive increase in
neutrophils (>50 x 109/L) as a reactive phenomenon is known as a leukaemoid reaction.

Neutrophils generally exhibit characteristic changes in response to infection. The neutrophils tend to be more immature, as
they are being released earlier. This is called a left shift . In a severe infection the neutrophils may show toxic granulation
and other toxic changes such as vacuolation and the presence of Döhle bodies.

The most common causes are:

• Bacterial infection
• Steroid therapy
• Post-surgery
• Extreme exercise
• Tissue necrosis
• Burns
• Systemic vasculitis
• Carcinoma
 CAUSES OF NEUTROPHILIA

1. A number of drugs have been demonstrated to increase the neutrophil count, including steroids, lithium, clozapine and
adrenalin.
2. Nervousness may very slightly raise the neutrophil count because of the effect of steroid release.

3. Pregnancy is associated with a slight increase in total neutrophil count demonstrating a left shift. Most laboratories
provide pregnancy specific reference ranges.

4. Persistent elevation of neutrophils may be a sign of chronic myeloid leukaemia (CML).

N.B: (Chronic myeloid leukaemia)

5. CML occurs in all age groups but most commonly in the middle aged and elderly.
6. The annual incidence is estimated at 1 - 2 cases per 100,000
7. Characteristic changes are a moderate increase in neutrophil count (usually >50 x 109/L), with a left shift and a
prominence of myelocytes. Basophilia and/or eosinophilia may also be present.
8. Chronic mild neutrophilia without left shift is very unlikely to be due to CML.
 EVALUATING NEUTROPHILIA
Neutrophilia represents either a reactive phenomenon (leukemoid reaction) or a myeloid malignancy.
A leukemoid reaction often is associated with infection, inflammation, malignancy, or use of drugs including glucocorticoids,
psychiatric medications, and myeloid growth factors.

I.E : patient history and findings on physical examination dictate whether further laboratory investigation is necessary to
determine the cause of the increased WBC count.

Further evaluation, if indicated, starts with a PBS that may show circulating blasts (suggesting acute leukemia), leuko-
erythroblastic results (suggesting myelofibrosis with myeloid metaplasia or other marrow-infiltrating process), or simply left-
shifted neutrophilia.
Left-shifted neutrophilia suggests either CML or another myeloproliferative disorder.
A leukemoid reaction must be distinguished from both conditions, and neither the degree of left-shifted granulocytosis nor the leukocyte
alkaline phosphatase score is considered diagnostically adequate. Therefore, if the patient’s history does not suggest a leukemoid reaction, so
a peripheral blood Interphase fluorescence in situ hybridization( IFISH) for bcr/abl to rule out the possibility of CML in mild cases of mature
neutrophilia (WBC, <20 × 109/L) is recommended.
A hematology consultation is required in the presence of either a higher degree of leukocytosis or left-shift .
THE LEUKOCYTE
ALKAINE
PHOSPHATASE (LAP)
The leukocyte alkaine phosphatase (LAP)
score is often used in patients with an elevated
WBC to differentiate a reactive process from
chronic myelogenous leukemia.
The score in the latter is low while it is within
the normal reference range or elevated in the
former condition.
Naphthyl AS-B1 phosphate is hydrolyzed to
phosphate and an aryl maphthylthalamide by
alkalline phosphatase in the cytoplasm of
WBCs. The aryl naphthylthalamide is coupled to
diazonium salt (fast red violet LB) forming an
insoluble blue dye within the cytolasm of the
WBCs. Neutrophils and bands are scored (0 to
4+) and the total score of 100 of these cells is
the LAP score. Variable intensity of blue
staining can be seen in the leukocytes in this
peripheral smear from a patient with a reactive
leukocytosis
Eosinophils
In most people eosinophils make up about 1-6% of white blood cells. The normal concentration of eosinophils is 0 - 0.5 x
109/L. Eosinophils persist in the circulation for 8 - 12 hours, and can survive in tissue for an additional 8 - 12 days in the
absence of stimulation.

EOSINOPHILIA (LOW EOSINOPHIL COUNT)

Eosinopenia is difficult to demonstrate in practice because of the low frequency of eosinophils in most healthy people. As
a result a low eosinophil count should not be a cause for concern.

EOSINOPHILIA (HIGH EOSINOPHIL COUNT)

In developed countries the most common causes are allergic diseases such as asthma and hay fever, but worldwide the
main cause of increased eosinophils is parasitic infection.
Rarer causes may entail
A. Hodgkins disease
B. Myeloproliferative disorders
C. Churg-Strauss syndrome
FOLLOW UP

Total eosinophil count Follow-up

< 1.0 × 109/L Trivial, ignore
Up to 1.5 × 109/L Probably ignore
> 1.5 × 109/L Consider possible causes

Haematology assessment is appropriate for patients with persistent (more than six months) moderate
eosinophilia, or marked or increasing eosinophilia.
Basophils

Basophils are the least common of the white cells, representing about 0.01 - 0.3% of all white blood cells. The
normal concentration of basophils is 0 - 0.2 x 109/L
The function of basophils is not fully understood, but it is known that they are capable of phagocytosis and
producing histamine.

BASOPENIA (LOW BASOPHIL COUNT)

Basopenia is difficult to demonstrate as the normal basophil count is so low.

BASOPHILIA (HIGH BASOPHIL COUNT)

The basophil count will only very rarely be significantly raised. When present, it may indicate a
myeloproliferative disorder, or other more obscure causes. A repeat CBC a week or two later may help.
 LYMPHOCYTES
Lymphocytes normally represent 20 - 40% of circulating white blood cells. The normal concentration of
lymphocytes is between 1.0 - 4.0 x 109/L.
There are two broad morphologic categories of lymphocytes which can be distinguished under the light
microscope, large granular lymphocytes and small lymphocytes.
Functionally distinct subsets of lymphocytes do not correlate with their appearance.

LYMPHOCYTOPENIA (LOW LYMPHOCYTE COUNT)

1. Low lymphocyte counts are not usually significant.

2. Characteristic decreases in the lymphocyte count are usually seen late in HIV infection, as T lymphocytes
(CD4+ T cells) are destroyed.
3. Steroid administration may reduce lymphocyte counts.
4. More rarely lymphocytopenia may be caused by some types of chemotherapy or malignancies.
5. People exposed to large doses of radiation, such as those involved with situations like Chernobyl, can have
severe lymphocytopenia
LYMPHOCYTOSIS (HIGH LYMPHOCYTE COUNT)

1. Increases in the absolute lymphocyte count are usually due to acute infections, such as Epstein-Barr virus infection
and viral hepatitis.
2. Less commonly, increased lymphocytes may be the result of pertussis and toxoplasmosis or (rarely) chronic
intracellular bacterial infections such as tuberculosis or brucellosis.
3. Also,The lymphocyte count may also be elevated in:

A. Smoking (reactive)
B. Hyposplenism (usually following splenectomy)
C. Acute stress response - usually seen in hospital setting, uncommon in community, usually resolves within 24 hours
D. Acute cardiac event
E. Trauma
F. Autoimmune thyroiditis
 EVALUATING LYMPHOCYTOSIS
The first step in the evaluation of lymphocytosis is a PBS to review the morphology of the excess lymphocytes.
WHY??
Reactive lymphocytosis is characterized by LGL morphology and must be distinguished from LGL leukemia.
What is LGL morphology?
Large granular lymphocytes (LGLs) have abundant, pale blue cytoplasm with distinct medium to large azurophilic cytoplasmic granules. ... LGL leukemia is a rare
disease characterized by an increase in circulating LGLs in excess of 2 × 10 9/L.

In some cases lymphocyte surface markers may be recommended for differentiating between reactive lymphocytosis and
lymphoproliferative disorders.
Because they do not affect management of asymptomatic patients with early stage disease, they are usually only indicated
when:
1. The lymphocyte count is persistently >6 - 7 x 109/L;
2. The lymphocytes demonstrate abnormal features;
3. Other blood count parameters are abnormal;
4. There are signs or symptoms suggestive of lymphoma (fever, sweats, weight loss, lymphadenopathy,
hepatosplenomegaly
 Monocytes
Monocytes constitute between 3 - 8% of all white cells in the blood. They circulate in the bloodstream for about one to
three days and then typically move into tissues (approx 8 - 12 hours) to sites of infection. The normal concentration of
monocytes is between 0 - 1.0 x 109/L.

Monocytes which migrate from the bloodstream to other tissues are called macrophages. Macrophages have a role in
specific immunity and phagocytosis.
MONOCYTOSIS (HIGH MONOCYTE COUNT)
Most often, elevated monocyte counts are associated with infection and inflammatory processes and will be seen in
conjunction with other blood count changes.
Isolated increases in the monocyte count, not accompanied by other changes in the blood count, are uncommon but may be
associated with:
•Chronic infection including tuberculosis
•Chronic inflammatory conditions (e.g. Crohn’s disease, ulcerative colitis, rheumatoid arthritis, SLE)
•Dialysis
•Early sign of chronic myelomonocytic leukaemia (rare)
•N.B:Absolute monocytosis that is persistent should be considered a marker of a myeloproliferative disorder (eg, chronic myelomonocytic leukemia) until
proved otherwise by bone marrow examination and cytogenetic studies
If levels are persistently elevated (i.e. > 1.5 x 10 9/L), particularly in association with suspicious symptoms, a haematology
referral may be prudent.
A mild elevation of monocytes is relatively common and does not usually require follow-up.
 PLATELETS

Also called Thrombocytes.

Platelets are produced by budding off from megakaryocytes in the bone marrow. Each megakaryocyte
produces between 5,000 to 10,000 platelets.
Platelets circulate for approximately one to two weeks and are destroyed by the spleen and liver.
A normal platelet count ranges from 150 - 450 x 109/L.
THROMBOCYTOPENIA (LOW PLATELET COUNT)
Interpretation of a low platelet count involves consideration of the clinical context.
Severe thrombocytopenia is associated with an increased risk of bleeding and requires urgent assessment.
It is particularly significant if accompanied by other changes in the CBC or the platelet count is falling.
Bleeding is unusual at platelet counts of >50 x 109/L unless there is an associated platelet function defect (which is uncommon).
Causes
Thrombocytopenia may be artefactual due to a variety of causes, which are worth excluding before looking for clinical causes,
including:
1. Partially clotted sample.
2. Platelet clumping in the blood collection tube.
The laboratory will usually look for evidence of these, but if the platelet count is not consistent with the clinical picture, a repeat
sample may be warranted.
Causes of isolated thrombocytopenia include:
Viral infection
Idiopathic thrombocytopenic purpura (ITP)
Medications
Liver disease
Autoimmune disease
Hypersplenism
HIV infection
Pregnancy
Bone marrow causes
Thrombocytopenia may also occur in conjunction with microangiopathic haemolysis (usually apparent on blood film
examination) in haemolytic uraemic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP) and chronic or acute
disseminated intravascular coagulation (DIC). TTP should be considered if the patient is febrile, unwell or has
neurological symptoms.
Follow-up
Low platelets are reasonably common, but it is important that results be interpreted in context, looking for clues to help.
Further testing that should be considered in patients with persistently low platelets includes a blood film, ANA (anti-
nuclear antibodies), HIV, Hepatitis B and C and liver enzymes. In some cases of chronic thrombocytopenia, Helicobacter
pylori serology and anticardiolipin antibodies may be indicated. Splenomegaly and lymph nodes should be checked on
examination.
Recommended follow up for thrombocytopenia:

Platelet count Referral

< 30 × 109/L Requires urgent referral
30 – 100 × 109/L Judgment depending on context. Urgent referral if
bleeding. Needs further investigation if
persistent/progressive. Refer if no cause found.
100 – 145 × 109/L Follow up counts. Investigate if persistent. Refer if
progressive without obvious cause.
THROMBOCYTOSIS (HIGH PLATELET COUNT)

• Elevated platelet levels may be a reactive change and will not necessarily signal any
clinical problem.
• Generally, a reactive thrombocytosis is not associated with an increased thrombotic
risk.
• Rarely will a thrombocytosis reflect a myeloproliferative disorder such as essential
thrombocythaemia or myelofibrosis.
These should particularly be considered if:
A. There is a chronic persistent elevation in platelet counts (more than six months) or
B. A very high platelet count without an obvious reactive cause.
C. They may also be associated with splenomegaly and the platelet count is usually >600
x 109/L (and often much higher).
CLINICAL CASES
History: CBC
70 year old female. (with microscopic differential)
Symptoms of dyspnea on exertion, easy fatigability, and
lassitude for past 2 to 3 months. RBC 3.71 x 1012/L
Denied hemoptysis, GI, or vaginal bleeding. Claimed diet was HGB 5.9 g/dL
good, but appetite varied. HCT 20.9 %
Physical Exam: MCV 56.2 fL
Other than pallor, no significant physical findings were noted. MCH 15.9 pg
Occult blood was negative. MCHC 28.3 g/dL
Her CBC is as shown. RDW 20.2

WBC 5.9 x 109/L

Q1: What morphologic alterations are seen in this blood smear N 82 %
field? L 13
Q2:What further laboratory studies, if any, are indicated? M 1
E 4
B 0

PLT 383 x 109/L

Morphologic Alterations
Further Laboratory Studies
Results of the blood smear exam were:
Iron studies were performed, and results were:
RBC morphology:
serum ferritin <10 ng/mL (RI 12-86)
hypochromasia
serum iron 24 µg/dL (RI 65-175)
microcytosis
TIBC 729 µg/dL (RI 250-410)
anisocytosis
saturation 3% (RI 20-55)
WBC morphology:
Within normal limits

PLT morphology:
spacerWithin normal limits

Q3:What is the most likely diagnosis?

Iron deficiency anemia

Clinical Course
Diagnostic procedures included upper GI endoscopy, colonoscopy, and small bowel biopsy. All were negative.

The patient received packed RBC transfusions and was started on iron therapy.

She refused any further laboratory testing or other procedures, and was discharged at her own request. She was lost to
follow-up.

The etiology of her iron deficiency anemia could not be determined, but it was most likely nutritional.
 CASE 2
CLINICAL HISTORY

Patient is a 49 year old male who does not have a significant past medical history until he developed tooth pain. He was
found to have tooth abscesses which were treated with antibiotics. A month later, he had his wisdom teeth pulled and
experienced delayed healing and persistent pain. He then began to feel fatigued, weak, and dyspnea on exertion,
prompting a visit to his primary care doctor. Laboratory studies revealed pancytopenia resulting in a bone marrow
biopsy.
Peripheral Blood:
The results of the CBC are illustrated in table 1

Q1: What morphologic alterations are

seen in this blood smear field?
PATIENT HISTORY:

The patient is a 19-year-old male with a two-week history of febrile illness, respiratory failure, and septic shock. His
illness started with low grade fever, intermittent headache, and nausea. Gradually, his symptoms progressed into high
fever, prominent weakness, shortness of breath, and respiratory failure.

Past medial history: No significance.

Social history: He lives at a home in a farm area with history of exposure to the dog, cat, and rodent.

Physical examination showed a few areas of ecchymosis, jaundice and hepatosplenomegaly.

Laboratory results
Q1: What morphologic alterations are seen in this blood smear field?
 WBC 19.11ˣ109/L
What morphologic alterations are seen in this blood smear field?
Neu% 5.4
Lym% 69.6
Mon% 24.7
Eos% 0.1
Bas% 0.2
RBC 1.45ˣ1012
HGB 4.1g/dl
HCT 12.7%
MCV 87.6 Fl
MCH 28.3 Pg
MCHC 32.3 g/Dl
PLT 5ˣ109/L
History
A 63-year-old woman goes to her general practitioner (GP) complaining of extreme tiredness.
She has been increasingly fatigued over the past year but in recent weeks she has
become breathless on exertion, light-headed and complained of headaches. Her feet have
become numb and she has started to become unsteady on her feet. She has had no significant
previous medical illnesses. She is a retired teacher and lives alone. Until the last
2 years she was active, walking 3 or 4 miles a day. She is a non-smoker and drinks about
15 units of alcohol per week. She is taking no regular medication. Her mother and one of
her two sisters have thyroid problems.
Examination
Her conjunctivae are pale and sclerae are yellow. Her temperature is 37.8°C. Her pulse rate
is 96/min regular, and blood pressure 142/72 mmHg. Examination of her cardiovascular,
respiratory and abdominal systems is normal. She has a symmetrical distal weakness
affecting her arms and legs. Knee and ankle jerks are absent and she has extensor plantar
responses. She has sensory loss in a glove and stocking distribution with a particularly
severe loss of joint position sense.
Haemoglobin 4.2 g/dL 11.7–15.7 g/dL
Mean corpuscular volume (MCV) 112 fL 80–99 fL
White cell count 3.3 % 109/L 3.5–11.0 % 109/L
Platelets 102 % 109/L 150–440 % 109/L
Sodium 136 mmol/L 135–145 mmol/L
Potassium 4.4 mmol/L 3.5–5.0 mmol/L
Urea 5.2 mmol/L 2.5–6.7 mmol/L
Creatinine 92 &mol/L 70–120 &mol/L
Glucose 4.4 mmol/L 4.0–6.0 mmol/L
Bilirubin 45 mmol/L 3–17 mmol/L
Alanine transaminase 33 IU/L 5–35 IU/L
Alkaline phosphatase 263 IU/L 30–300 IU/L

INVESTIGATIONS
Questions
• What is the diagnosis?
• How would you investigate and manage this patient?