WBC disorders 1

Question 1

Lymphopenia

Answer 1

Clinical settings for lymphopenia:
• Advanced HIV infection
• Drug-induced: cytotoxic chemotherapy, steroid therapy • Autoimmune disease
• Acute viral infections

Question 2

Neutropenia: Pathogenesis

Answer 2

• Reduced or Ineffective Production→problem in the bone marrow
• Accelerated Consumption/Destruction→problem in the periphery

Question 3

Neutropenia due to Reduced Production

Answer 3

• Suppression of myeloid stem cells (aplastic anemia, usually idiopathic).
• Suppression of committed myeloid precursors (often drug- induced).
• Ineffective granulopoiesis (e.g., megaloblastic anemias, myelodysplastic syndromes).
• Marrow infiltration (granulomatous inflammation, tumors).
• Rare inherited disorders (Kostmann syndrome).

Question 4

Neutropenia due to Peripheral Loss

Answer 4

• Immune-related (idiopathic autoimmune disease, drugs).
• Splenic sequestration (splenomegaly).
• Increased consumption (overwhelming infection).

Question 5

Clinical Implications of Neutropenia

Answer 5

Agranulocytosis: severe neutropenia, prone to life-threatening infections (<500 cells/μl).

-Severe neutropenia is most commonly drug-induced
• Predictable, dose-related – e.g., chemotherapy
• Idiosyncratic – many drugs, usually immune-mediated, by suppression of marrow precursors

Question 6

Clinical features of Neutropenia

Answer 6

• Symptoms and signs related to infections
• Empirical treatment with broad-spectrum antibiotics.
• In predictable neutropenia, such as following myelosuppressive chemotherapy, treatment regimens include G-CSF (granulocyte colony stimulating factor)

Question 7

Neutrophilic Leukocytosis seen in:

Answer 7

• Infections – pyogenic bacteria.
• Sterile inflammation – tissue damage (MI, burns, trauma, surgery)
• Acute inflammation (gout, rheumatoid arthritis)
• Acute hemorrhage.
• Malignancy - extensive/necrotic tumors.

Question 8

Eosinophilic Leukocytosis seen in:

Answer 8

• Allergic disorders (asthma, hay fever).
• Skin diseases (Bullous Pemphigus & Pemphigoid, Dermatitis
Herpetiformis).
• Parasitic infestations.
• Drug reactions.
• Malignancies (lymphomas – Hodgkin’s, T-cell lymphoma).
• Collagen vascular diseases, vasculitis.

Question 9

Basophilic Leukocytosis seen in

Answer 9

Basophilic leukocytosis is rarely reactive, and almost always indicates myeloproliferative neoplasm
(especially Chronic Myeloid Leukemia - CML).

Question 10

Monocytosis seen in

Answer 10

• Chronic infections (e.g. Tuberculosis, rickettsiosis, bacterial endocarditis, malaria).
• Collagen vascular diseases (e.g. Systemic lupus erythematosus).
• Inflammatory bowel diseases (e.g. Ulcerative colitis).

Question 11

Lymphocytosis seen in

Answer 11

• Many disorders with chronic immunologic stimulation, often also associated with monocytosis (e.g. TB).
• Viral infections (EBV, Hep A, CMV). • B. Pertussis infection.

Question 12

Infectious Mononucleosis & Atypical Lymphocytes

Answer 12

• Infection of B-cells by Epstein-Barr virus
• Young adults and adolescents – direct oral transmission (Kissing disease)

Question 13

Clinical features of Mono

Answer 13

• Acute onset of fever, sore-throat
• Lymphocytosis of activated CD8 T cells – become activated lymphocytes that infiltrate lymph nodes, spleen& portal tracts (generalized lymphadenitis & Splenomegaly)

Question 14

Pathogenesis of WBC neoplasms

Answer 14

• Chromosomal translocations and oncogenes – non- random chromosomal abnormalities are frequent in WBC neoplasms.
• Inherited genetic factors e.g., Down syndrome.
• Viruses e.g., EBV, HTLV-1, KSHV/HHV-8.
• Environmental agents e.g., H.pylori, immune dysregulation in HIV
• Iatrogenic e.g., radiation, chemotherapy.

Question 15

Leukemia

Answer 15

Neoplasia involves predominantly bone marrow at the time of presentation→spills over into blood- tumor cells can be myeloid or lymphoid

Question 16

Lymphoma

Answer 16

Neoplasia forms discrete tissue masses (lymph nodes or extra-nodal) at the time of presentation- tumor cells are lymphoid

Question 17

Acute leukemia

Answer 17

• Acute onset (days to weeks)
• Aggressive and fatal if not treated
• Immature and undifferentiated neoplastic cells (blasts)
• Can be lymphoid or myeloid

Question 18

Chronic Leukemia

Answer 18

• Insidious onset
• Slowly progressive but can transform into acute
• Mature and more differentiated neoplastic cells
• Can be lymphoid or myeloid

Question 19

FAB Classification of AML

Answer 19

8 groups, AML M0 to M7, were based on:
• Degree of maturation of granulocytic lineage AMLs (M0, M1, M2, M3).
• Presence of Additional Lineages of blast cells (M4, M5, M6, M7).

Question 20

Special features of AML groups

Answer 20

• M2- Most common variety
• M3- Hyper granular promyelocytes- Procoagulant factors- DIC, t(15;17), fusion of PML and RARA genes blocks maturation of promyelocytes to myelocytes. Treated with All trans retinoic acid(ATRA)- promotes maturation
• M4, M5- monoblasts infiltrating gums- hypertrophied gums
• M7- association with Down syndrome

Question 21

Pathogenesis of AML

Answer 21

1. Translocations disrupt genes encoding transcription factors for normal differentiation. Chimeric genes→abnormal fusion proteins →block in terminal differentiation
2. Additional steps e.g. mutated tyrosine kinases with persistent aberrant activation, lead to increased cellular proliferation
3. Accumulation of proliferating neoplastic precursors in the BM
   suppresses normal hematopoietic progenitors