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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 = MCQshttp://www.hematologyatlas.com/http://pathy.med.nagoya-u.ac.jp/atlas/doc/atlas.html

Final Theoretical exam : 40Final Practical exam : 20 (including written questions)1st Periodic exam : 10 theory, 5 Practical 2nd Periodic exam : 10 theory, 5 PracticalHomework and class activities : 5 Theory, 5 PracticalTotal : 100

Marks

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ObjectivesTo 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 Immunocytes(Granulocytes) (A granulocytes)

Neutrophils LymphocytesEosinophils small & Large

Basophils B & T Lymphocytes

Monocytes*

*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

DefinitionTWBC 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.)

GranulocytosisIncrease 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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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).

Leukemoid reactions

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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 dependentCount rarely exceeds >1.0 x 109/LHave no marrow reservesCauses 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 granulocytesReference range for adult is 0 – 0.2 x 109/LMost commonly associated with hypersensitivity reactions to drugs or foodInflammatory conditions e.g RA, ulcerative colitis are also sometime associated with basophiliaMyeloproliferative disordersChronic myeloid leukemia

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(LYMPHOCYTOSIS)

The blood contain only few percent of total body lymphocytesThe most consistent variation is seen with ageAlteration 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 acquired

Pelger-Huet anomaly Toxic granulation

Neutrophil hyper-segmentation Dohle bodies May-Hegglin anomaly Pelger cellsAlder’s anomaly Hypersegmented

neutrophils Chediak-Higashi syndrome

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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 negative1. Does the student has Neutrophilia OR Lymphocytosis?2. Explain your answer in Q13. 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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