Neutropenia, Agranulocytosis
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Transcript of Neutropenia, Agranulocytosis
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LEUKOPENIAAbnormally LOW WBC
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NEUTROPENIA, AGRANULOCYTOSIS
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NEUTROPENIA◦Reduction in the number of granulocytes in PBS
(peripheral blood smear)< 2000/uLMild 1000-2000/uLModerate 500-1000/uLSevere (agranulocytosis) <500/uL
DEFINITION:
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AGRANULOCYTOSIS◦Marked reduction in neutrophil count
◦Disappearance of neutrophil precursors in the bone marrow
◦Absence or less than 500/uL of pmns
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1. INEFFECTIVE GRANULOPOIESIS
2. ACCELERATED REMOVAL OR DESTRUCTION OF NEUTROPHILS
PATHOGENESIS:
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Stem Cell
Common Myeloid Progenitor
CFU - GM
CFU-G
Myeloblast
Neutrophil
CFU-M
Monoblast
Monocyte
CFU- b/Mg
/E
CFU-B
Basophiloblast
Basophil
CFU-Mg
Megakyroblast
Plastelet
BFU-E
Proerythroblast
Erythrocyte
IL-5
CFU-eoEosinoblast
Eosinophil
Common Lymphoid Progenitor
Multipotent
Progenitors
Commited
Precursors
Late Precuros
ors
Mature
Form
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INEFFECTIVE GRANULOPOIESIS
Suppression of hematopoietic stem cells◦ Aplastic anemia◦ Infiltrative d/o
Suppression of committed granulocytic precursors ◦ Alkylating drugs –
generalized effect◦ Idiosyncratic reaction
– Chloramphenicol
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Defective precursor cells susceptible to death while in BM◦Megaloblastic
anemia Genetic defect
impaired granulocytic differentiation : Kostmann syndrome
INEFFECTIVE GRANULOPOIESIS
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Immune mediated◦Idiopathic◦ Autoimmune◦Drugs
Splenic sequestration◦20 to enlargement of spleen
Increased peripheral utilization◦Overwhelming infection
ACCELERATED REMOVAL/DESTRUCTION
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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:
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S/S Related to infection◦Malaise, chills, fever◦Marked weakness & fatigue
Death in severe agranulocytosis◦Neutrophil count < 500/mm3
CLINICAL COURSE:
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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:
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LEUKOCYTOSISINCREASE IN NUMBER OF WBC REACTIVEFIRST SIGN OF NEOPLASTIC GROWTH OF WBC
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Pathogenesis
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INCREASED RELEASE • Endotoxemia• Acute INFXN• Hypoxia
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DECREASED MARGINATION• EXERCISE• EPINEPHRINE
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• GlucocorticoidsDECREASED
EXTRAVASATION
• Chronic INFXN• Tumors• Myeloproliferative D/O
INCREASED NUMBERS OF
MARROW PRECURSORS
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NEUTROPHILIC
•Acute Bacterial•Sterile Inflammation•Burn, MI
EOSINOPHILIC
•Allergic•Parasitic•Drug reaction•Lymphoma•Collagen vasc. Disease
CAUSES:
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Basophilic
• Myeloproliferative D/O• CML
Lymphocytosis
• ( Commonly w/ monocytosis )
• Chronic Immunologic Stimulation• TB
• Viral • Lymphocytic
Leukemia/Lymphoma
CAUSES:
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ACUTE NONSPECIFIC LYMPHADENITIS
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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:
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Enlarged Tender to touchFluctuant if (+) abscessDraining sinuses to skin
◦Suppurative necrosis
Clincal Presentation:
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CHRONIC NONSPECIFIC
LYMPHADENITISMORPHOLOGIC TYPES
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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
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Morphology
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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
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PARACORTICAL LYMPHOID HYPERPLASIA
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Distention of lymphatic sinusoids Non-specificParticularly prominent in LN draining cancers Represent host immune reaction to cancer
Sinus Histiocytosis
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Sinus Histiocytosis