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Benign disorders of WBCs
By/
Mr. Waqqas Elaas;
M.Sc; MLT
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References
For theory : Essential Haematology, John Wiley & Sons Ltd ,6th Edition,Victor
Hoffbrand.
For practical : Practical Haematology, Churchill Livingstone, Eighth edition, John
V. Dacie, S. M. Lewis,
Internet site(s):
http://www.essentialhaematology6.com/default.asp = MCQs
http://www.hematologyatlas.com/
http://pathy.med.nagoya-u.ac.jp/atlas/doc/atlas.html
Marks
Final Theoretical exam : 40
Final Practical exam : 20 (including written questions)
1st Periodic exam : 10 theory, 5 Practical
2nd Periodic exam : 10 theory, 5 Practical
Homework and class activities : 5 Theory, 5 Practical
Total : 100
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Objectives
To differentiate between the qualitative & quantitative WBCs benign
disorders.
To understand the etiology and pathology of reactive changes in the
number and morphology of granulocytes.
To understand the etiology and pathology of reactive changes in the
number and morphology of lymphocytes and monocytes.
To know the definition & causes of Infectious Mononucleosis.
To know the definition & causes of Leukemoid reactions.
To be able to differentiate between Eosinophilia & Hypereosinophilic
syndromes.
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Leucocytes (WBCs)
Phagocytes
(Granulocytes)
Neutrophils
Eosinophils
Basophils
Monocytes*
Immunocytes
(A granulocytes)
Lymphocytes
small & Large
B & T Lymphocytes
*sometimes Monocytes are considered as A granulocytes
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Normal leucocytes morphology
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LEUCOCYTES BENIGN DISORDERS
Quantitative


Change in number
Terminology


Cytosis / philia
 Increase in number
Cytopenia/penia
 Decrease in number
Qualitative


Morphologic changes
Functional changes
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LEUCOCYTES BENIGN DISORDERS
Quantitative changes
Relative & Absolute values
To make an accurate assessment, consider both relative and
absolute values. For example a relative value of 70%
neutrophils may seem within normal limits; however, if the total
WBC is 20,000, the absolute value (70% of 20,000) would be an
abnormally high count of 14,000.
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LEUCOCYTOSIS
Definition
Raised TWBC above 11.0 x 109/L in adults, due to
elevation of any of a single lineage.


Note: elevation of the minor cell populations can
occur without a rise in the total white cell count.
Normal reference range (adults)

4.5 -- 11.0 x 109/L
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LEUCOPENIA
Definition
TWBC lower than 4.5 x 109/L in adults
 Leucopenia may affect one or more lineages and it
is possible to be severely neutropenic or
lymphopenic without a reduction in total white cell
count.
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(contd.)
Granulocytosis
Increase in the count of all or one of
the granulocytic component:



Neutrophils
Basophils
Eosinophils
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NEUTROPHILIA
Definition



Increase in the number of neutrophils and / or its
precursors
In adults count >7.5 x 109/L but the counts are age
dependent
Increase may results from alteration in the normal
steady state of




Production
Transit
Migration
Destruction
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NEUTROPHILIA (contd.)
Causes of Neutrophilia

Infection
 Bacterial

Inflammatory conditions
 Autoimmune disorders
 Gout


Neoplasia
Metabolic conditions
 Uraemia
 Acidosis
 Haemorhage



Corticosteroids
Marrow infiltration/fibrosis
Myeloproliferative disorders
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Leukemoid reactions

Excessive reactive leucocytosis.
 Applied to chronic Neutrophilia with marked leucocytosis (>20 x
109/L)
 The usual feature is the shift to the left of myeloid cells
 Causes include



Infections
Marrow infiltration
Systemic disease (e.g.: Acute liver failure)
(Left shift : indicates that the neutrophils present in the blood are at a slightly
earlier stage of maturation than usual. The Band and the stages before. This is
often seen in acute infections).
(Right shift : an increase in the percentage of multilobed neutrophils).

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NEUTROPENIA
Neutropenia is an absolute reduction in the
number of circulating neutrophils



Mild (1- 1.5 x 109/L)
Moderate (0.5 – 1 x 109/L)
Severe (<0.5 x 109/L)
 Symptoms are rare with the neutrophil count above 1
x 109/L
 Bacterial infections are the commonest.
 Fungal, viral and parasitic infection are relatively
uncommon.
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(NEUTROPENIA) contd.
Causes of Neutropenia






Racial
Congenital
Marrow aplasia
Marrow infiltration
Megaloblastic anemia
Acute infections
 Typhoid, Miliary TB, viral hepatitis



Drugs
Irradiation exposure
Immune disorders
 HIV
 SLE
 Neonatal isoimmune and autoimmune neutropenia

Hyperslplenism
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(EOSINOPHILIA)
Increase in the eosinophil count must prompt for
further investigation (>0.6 x 109/L)
The causes of eosinophilia can be considered
under following headings







Allergy
 Atopic, drug sensitivity and pulmonary eosinophilia
Infection
 Parasites, recovery from infections
Malignancy
 Hodgkin’s disease, NHL and myeloproliferative disorders
Drugs
Skin disorders
Gastrointestinal disorders
Hypereosinophilic syndrome
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(EOSINOPHILIA) Contd.
Hypereosinophilic syndrome

Criteria of diagnosis





Peripheral blood eosinophil >1.5 x 109/L
Persistence of counts more than 6 months
End organ damage
Absence of any obvious cause for eosinophilia
Organ most commonly involved




Heart
Lung
Skin
Neurological
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(MONOCYTOSIS)
Absolute monocyte count is age dependent
Count rarely exceeds >1.0 x 109/L
Have no marrow reserves
Causes of monocytosis can be grouped as

Infections
 Chronic infection (TB, typhoid fever, infective endocarditis)
 Recovery from acute infection

Malignant disease
 MDS, AML, HD, NHL

Connective tissue disorders
 Ulcerative colitis, Sarcoidosis, Crohn’s disease

Post splenectomy
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(BASOPHILIA)
Basophils are least common of the granulocytes
Reference range for adult is 0 – 0.2 x 109/L
Most commonly associated with hypersensitivity reactions
to drugs or food
Inflammatory conditions e.g RA, ulcerative colitis are also
sometime associated with basophilia
Myeloproliferative disorders
Chronic myeloid leukemia
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(LYMPHOCYTOSIS)
The blood contain only few percent of total body
lymphocytes
The most consistent variation is seen with age
Alteration of lymphocyte counts can result from




The redistribution of lymphocytes
Absolute increase of lymphocyte number
Loss of lymphocytes
Combination of these
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(LYMPHOCYTOSIS)
Non-malignant causes of lymphocytosis

Infections
 Viral infections



Infectious mononucleosis
CMV
Rubella, hepatitis, adenoviruses, chicken pox,dengue
 Bacterial infections


Pertussis
Healing TB, typhoid fever
 Protozoal infections





Toxoplasmosis
Allergic drug reactions
Hyperthyroidism
Splenectomy
Serum sickness
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(LYMPHOCYTOSIS)
Infectious Mononucleosis





Epstein-Barr virus
Saliva from infected person is the main contagion
Virus infect epithelial cells and B cells
Infection in children under the age of 10 does not
cause illness and result in life long immunity
Clinical features




Fever, malaise, fatigue, sore throat, splenomegaly
Blood picture shows leucocytosis ( 10 – 20 x 109/L) due to
absolute increase in lymphocytes
Diagnosis is by serological tests
There is no specific treatment
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Qualitative changes (MORPHOLOGY)
Congenital
Pelger-Huet anomaly
Neutrophil hyper-segmentation
May-Hegglin anomaly
Alder’s anomaly
Chediak-Higashi syndrome
acquired
Toxic granulation
Dohle bodies
Pelger cells
Hypersegmented neutrophils
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LEUCOCYTES BENIGN DISORDERS
Qualitative changes (MORPHOLOGY)
Congenital

Pelger-Huet anomaly


Bilobed and occasional unsegmented neutrophils
Autosomal recessive disorder
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LEUCOCYTES BENIGN DISORDERS
Qualitative changes (MORPHOLOGY) contd.
 Neutrophil hyper-segmentation
 Neutrophil function is essentially normal

May-Hegglin anomaly
 Neutrophils contain basophilic inclusions of RNA
 Occasionally there is associated leucopenia,
Thrombocytopenia and giant platelet are frequent
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LEUCOCYTES BENIGN DISORDERS
Qualitative changes (MORPHOLOGY) contd.

Alder’s anomaly
 Granulocytes, monocytes and lymphocytes contain
granules which stain purple with Romanowsky stain
 Granules contain mucopolysaccharides
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LEUCOCYTES BENIGN DISORDERS
Qualitative changes (MORPHOLOGY) contd.

Chediak-Higashi syndrome
 Giant granules in granulocytes, monocytes and lymphocytes
 Depressed migration and degranulation
 Recurrent pyogenic infections
 Lymphoproliferative syndrome may develop
 Treatment is BMT
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LEUCOCYTES BENIGN DISORDERS
Qualitative changes (MORPHOLOGY) contd.
Acquired
 Toxic granulation
 Dohle bodies
 Pelger cells
 Hypersegmented neutrophils
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Homework
(1) Case : A 20-year-old student presented with a 7-day history of fever, sore
throat, lethargy and tender enlarged glands in the neck. Physical examination
reveals fever, mild jaundice, inflamed pharyngeal mucosa and cervical
adenopathy. Blood results
Hb; 12.5 g/dl, wbc 18.0x109/l , differential 30% neutrophils 40% lymphocytes 30%
abnormal lymphocytes. Platelets 100 x109/l. Throat swab: No bacterial growth
HIV test negative
1. Does the student has Neutrophilia OR Lymphocytosis?
2. Explain your answer in Q1
3. What is the probable diagnosis?
(2) Design a table containing the 5 types of leucocytes with their normal ranges in
adults.
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