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Neutropenia, Agranulocytosis
 

Neutropenia, Agranulocytosis

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    Neutropenia, Agranulocytosis Neutropenia, Agranulocytosis Presentation Transcript

    • LEUKOPENIA
      Abnormally LOW WBC
    • NEUTROPENIA, AGRANULOCYTOSIS
    • NEUTROPENIA
      Reduction in the number of granulocytes in PBS
      (peripheral blood smear)
      < 2000/uL
      Mild 1000-2000/uL
      Moderate 500-1000/uL
      Severe (agranulocytosis) <500/uL
      DEFINITION:
    • AGRANULOCYTOSIS
      Marked reduction in neutrophil count
      Disappearance of neutrophil precursors in the bone marrow
      Absence or less than 500/uL of pmns
    • PATHOGENESIS:
      1. INEFFECTIVE GRANULOPOIESIS
      2. ACCELERATED REMOVAL OR DESTRUCTION OF NEUTROPHILS
    • Multipotent Progenitors
      Commited Precursors
      Late
      Precurosors
      Mature
      Form
    • INEFFECTIVE GRANULOPOIESIS
      Suppression of hematopoietic stem cells
      Aplastic anemia
      Infiltrative d/o
      Suppression of committed granulocytic precursors
      Alkylating drugs – generalized effect
      Idiosyncratic reaction – Chloramphenicol
    • Defective precursor cells susceptible to death while in BM
      Megaloblastic anemia
      Genetic defect  impaired granulocytic differentiation : Kostmann syndrome
      INEFFECTIVE GRANULOPOIESIS
    • Immune mediated
      Idiopathic
      Autoimmune
      Drugs
      Splenic sequestration
      20 to enlargement of spleen
      Increased peripheral utilization
      Overwhelming infection
      ACCELERATED REMOVAL/DESTRUCTION
    • Most common cause is DRUG TOXICITY
      Alkylating drugs/ Anti-metabolites
      Generalized suppresion of BM  Agranulocytosis
      Predictable
      Dose related
      Chlorpromazine/ Phenothiaxines
      Toxinc effect on granulocytic precursors in BM
      Thiouracil/Sulfonamides/ Aminopyrine
      Antobody mediated destruction of mature neutrophils
      Autoantibodies against neutrophil specific antigens
      Suppression of marrow granulocytic progenitors by products of neoplastic cell
      Agranulocytosis:
    • S/S Related to infection
      Malaise, chills, fever
      Marked weakness & fatigue
      Death in severe agranulocytosis
      Neutrophil count < 500/mm3
      CLINICAL COURSE:
    • Broad spectrum antibiotic
      G-CSF , a growth factor that stimulates production of granulocytes from BM
      Given following chemotx
      Withdrawing or tapering dose of drug
      Treatment:
    • LEUKOCYTOSIS
      INCREASE IN NUMBER OF WBC
      • REACTIVE
      • FIRST SIGN OF NEOPLASTIC GROWTH OF WBC
    • Pathogenesis
    • CAUSES:
    • CAUSES:
    • ACUTE NONSPECIFIC LYMPHADENITIS
    • Reactive changes to:
      Microbe , Cell debris, Foreign matter
      Localized – Regional LN
      Generalized Lymphadenopathy
      Systemic Viral infection – Children
      Bacteremia
      Prominence of Lymphoid Follicles with Large germinal center, Debris, Macrophages, Necrosis, Suppuration
      Features:
    • Enlarged
      Tender to touch
      Fluctuant if (+) abscess
      Draining sinuses to skin
      Suppurative necrosis
      Clincal Presentation:
    • CHRONIC NONSPECIFIC LYMPHADENITIS
      MORPHOLOGIC TYPES
    • Activation of Humoral response
      Rheumatoid arthritis
      Early stage of HIV
      Must be differentiated from Follicular Lymphoma
      Germinal center B-cells are (+) for BCL2 stain
      FOLLICULAR HYPERPLASIA
    • Morphology
    • Trigger the Cellular Immune responses
      Reactive changes in T cell region of LN
      PARACORTICAL AREA EXPANSION
      EFFACED THR FOLLICLES
      Drugs – Dilantin
      Acute viral infxn
      IM
      Viral Vaccine
      PARACORTICAL LYMPHOID HYPERPLASIA
    • PARACORTICAL LYMPHOID HYPERPLASIA
    • Distention of lymphatic sinusoids
      Non-specific
      Particularly prominent in LN draining cancers
      Represent host immune reaction to cancer
      Sinus Histiocytosis
    • Sinus Histiocytosis