HemII_Disorders of leukocytes 3

MLT Diploma: Disorders of Leukocytes

Overview

  • Study of leukocyte disorders is critical in understanding various hematological conditions.

Page 1: Title Page

  • MLT Diploma: Focus on the disorders of leukocytes.

Page 2: Types of Disorders

Nonmalignant Disorders of Granulocytes & Monocytes

  • Platelets: Important for blood clotting.

  • Red Blood Cells: Carry oxygen throughout the body.

  • White Blood Cells: Leukocytes involved in immune response.

  • Definition of Leukocytes: White blood cells that play a key role in the immune system.

Page 3: Quantitative Leukocyte Abnormalities

Summary of Normal Ranges

  • Total WBC count:

    • At birth: 9-30 x 10^9/L

    • In children (average): 8 x 10^9/L

    • In adults: 3.5-11.0 x 10^9/L

  • Differential Count (adults):

    • Segmented neutrophils: 40-75%

    • Neutrophils-bands: 0-3%

    • Eosinophils: 1-6%

    • Basophils: 0.5-1%

    • Lymphocytes: 20-40% (up to 60% in children)

    • Monocytes: 2-8%

Page 4: Nonmalignant Disorders of Granulocytes & Monocytes

Types of Disorders

  1. Quantitative Disorders: Leukocytosis and leukocytopenia

  2. Morphological Abnormalities:

    • Toxic granulation

    • Döhle bodies

    • Hypersegmentation

    • Pelger-Huët anomaly

  3. Qualitative Disorders: Defective locomotion, chemotaxis, and microbicidal activity

Page 5: Leukocytopenia and Related Disorders

Causes of Leukocytopenia

  • Infections: Viral infections, overwhelming bacterial infections (sepsis)

  • Physical Agents/Chemicals: Radiation, benzene

  • Medications: Drugs and chemotherapy

  • Acute Leukemia: Certain types

  • Bone Marrow Damage: Injury or infiltration by malignant cells

  • Entrapment: In spleen

  • Others: Starvation

Types of Neutropenia

  • Agranulocytosis: Severe deficiency of neutrophils

  • Myelokathexis: Failure to release mature granulocytes

  • Transcobalamin-II deficiency: Affects vitamin B12 transport

  • Cyclic neutropenia: Periodic drops in neutrophil count

Causes

  • Transient due to infections or inflammatory reactions

  • Administration of anti-inflammatory drugs (glucocorticoids)

Eosinopenia & Basopenia

  • Eosinopenia: Rare; often seen post-infection or with glucocorticoids

  • Basopenia: Very rare; may occur in sepsis or with glucocorticoids

  • Monocytopenia: Difficult to establish, rarely occurs

Page 6: Morphological Abnormalities of Granulocytes

Common Anomalies

  1. Toxic Granulation:

    • Prominent granular appearance in neutrophils

    • Associated with severe infections, burns, malignant disorders

    • Grading system based on granule coarseness and amount

  2. Döhle Bodies:

    • Light gray-blue inclusions in neutrophils

    • Associated with infections, burns, chemotherapy

    • Appear as aggregates of rough endoplasmic reticulum with RNA

Page 7: Further Morphological Abnormalities

Hypersegmentation

  • Defined as neutrophils with >6 nuclear segments

  • Often linked to vitamin B12 or folic acid deficiency; shows macrocytic anemia

Page 8: Cytoplasmic Vacuoles

Appearance

  • Clear unstained areas in the cytoplasm of neutrophils and monocytes

  • Indicate phagocytosis; associated with toxic granulation and Döhle bodies

  • May occur as artifacts in blood smears from old specimens.

Page 9: Leukemoid Reaction

Definition

  • Reactive increase in WBC count resembling leukemia

  • Presence of immature neutrophils;

  • Resolves when underlying condition treated.

Associated Infections and Malignancies

  • Infections: Disseminated TB, Pertussis, Hepatitis

  • Non-bone marrow malignancies: Hodgkin's, gastric, breast, and lung cancers

Page 10: Nonmalignant Lymphocytic Disorders

Types of Lymphocytes

  1. T lymphocytes: Cell-mediated immunity

  2. B lymphocytes: Produce antibodies

  • Classes of T-lymphocytes:

    • T-helper cells

    • T-cytotoxic (killer) cells

Page 11: Causes of Lymphocytosis

Nonmalignant Causes

  1. Viral Infections: Infectious mononucleosis, active hepatitis, CMV

  2. Bacterial Infections: Bordetella pertussis, brucellosis

  3. Parasitic Infections: Toxoplasmosis

  4. Drug Reactions: Hypersensitivity reactions (e.g., Phenytoin)

  5. Uncommon Causes: Tertiary syphilis, smallpox

Page 12: Lymphocytopenia

Clinical Definition

  • Adults: <1.5 x 10^9 lymphocytes/L

  • Children: <3 x 10^9 lymphocytes/L

Causes

  1. Stress: Corticosteroid administration

  2. Medical Treatment: Radiation or cytotoxic drugs

  3. Immunodeficiencies: Congenital and acquired conditions

    • Examples: DiGeorge Syndrome, AIDS (lower T helper cells)

Page 13: Malignant Disorders of Leukocytes

Overview

  • Various forms and classifications exist.

Page 14: Understanding Cancer

Definition

  • Cancer involves uncontrolled growth of abnormal cells.

  • Can disrupt normal cell functions, leading to organ dysfunction.

Page 15: Forms of Leukemia

Classification

  • Acute vs. Chronic: Based on symptoms, cell maturity, and leukocyte count.

Acute Leukemia

  • Short duration symptoms;

  • Presence of immature cells;

  • Wide variation in WBC count.

Chronic Leukemia

  • Extended duration of symptoms;

  • Mostly mature leukocytes;

  • Elevated total WBC count.

Page 16: Incidence of Leukemias

  • ALL: More common in children

  • AML: Predominantly seen in adults

  • CLL: Rare in children, unusual before age 40

  • CML: Peak age 30-50

Page 17: Comparison Between Acute and Chronic Leukemias

Characteristics

Acute

Chronic

Age

All ages

Usually adults

Clinical Onset

Sudden

Insidious

Course (untreated)

6 months or less

2-6 years

Leukemic Cells

Immature ≥20% blasts

Mostly mature cells

Anemia

Prominent

Mild

Thrombocytopenia

Prominent

Mild

WBC Count

Variable

Increased

Lymphadenopathy

Mild

Present, often prominent

Splenomegaly

Mild

Present, often prominent

Page 18: Classification of Leukemia

FAB Classification

  • Based on morphology, cytochemical characteristics, and symptoms.

  • Types:

    1. Acute Lymphocytic Leukemia (ALL)

    2. Chronic Lymphocytic Leukemia (CLL)

    3. Acute Myelogenous Leukemia (AML)

    4. Chronic Myelogenous Leukemia (CML)

    5. Acute Monocytic Leukemia

    6. Chronic Monocytic Leukemia

  • Less Common Forms: Acute undifferentiated stem cell leukemia.

Page 19: WHO Classification

Latest Protocol

  • Fourth edition (2008) classifies neoplasms based on lineage and morphology,

  • Combines immunophenotyping and genetic study results for complete classification.

Page 20: Clinical Features of Leukemia

Common Symptoms

  • Systemic: Weight loss, fatigue, fever

  • Hematological: Frequent infections, anemia, bleeding tendencies

  • Physical Findings:

    • Enlarged lymph nodes

    • Splenomegaly

    • Hepatomegaly

  • Leukostasis: Hyper-leukocytosis leading to tissue infiltration.

Page 21: Diagnosis of Acute Leukemia

Required Tests

  1. Complete Blood Count (CBC)

  2. Blood Film: Identification of abnormal cells

  3. Cytochemical stains: To identify lineage

  4. Flow Cytometry: For lineage, subtype, and maturation stage

  5. Genetic Profiling: Identification based on cytogenetics

Page 22: Reporting WHO 2008 Subclassification

  • Detailed analysis of leukemic classification based on slides and laboratory data.