LEUKOPENIAAbnormally LOW WBC

NEUTROPENIA, AGRANULOCYTOSIS

NEUTROPENIA◦Reduction in the number of granulocytes in PBS

(peripheral blood smear)< 2000/uLMild 1000-2000/uLModerate 500-1000/uLSevere (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

1. INEFFECTIVE GRANULOPOIESIS

2. ACCELERATED REMOVAL OR DESTRUCTION OF NEUTROPHILS

PATHOGENESIS:

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

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:

LEUKOCYTOSISINCREASE IN NUMBER OF WBC REACTIVEFIRST SIGN OF NEOPLASTIC GROWTH OF WBC

Pathogenesis

INCREASED RELEASE • Endotoxemia• Acute INFXN• Hypoxia

DECREASED MARGINATION• EXERCISE• EPINEPHRINE

• GlucocorticoidsDECREASED

EXTRAVASATION

• Chronic INFXN• Tumors• Myeloproliferative D/O

INCREASED NUMBERS OF

MARROW PRECURSORS

NEUTROPHILIC

•Acute Bacterial•Sterile Inflammation•Burn, MI

EOSINOPHILIC

•Allergic•Parasitic•Drug reaction•Lymphoma•Collagen vasc. Disease

CAUSES:

Basophilic

• Myeloproliferative D/O• CML

Lymphocytosis

• ( Commonly w/ monocytosis )

• Chronic Immunologic Stimulation• TB

• Viral • Lymphocytic

Leukemia/Lymphoma

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 touchFluctuant if (+) abscessDraining sinuses to skin

◦Suppurative necrosis

Clincal Presentation:

CHRONIC NONSPECIFIC

LYMPHADENITISMORPHOLOGIC 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-specificParticularly prominent in LN draining cancers Represent host immune reaction to cancer

Sinus Histiocytosis

Sinus Histiocytosis