Leukocytosis - DSA Flashcards
List primary causes of neutrophilia
Hereditary neutrophilia Chronic idiopathic neutrophilia Pelter-Huet Anomaly Down Syndrome Leukocyte adhesion deficiency Familial cold urticaria Chronic myelogenous leukemia, myeloproliferative disorders Post splenectomy
List secondary causes of neutrophilia
Infection Chronic inflammation cigarette smoking stress drug induced nonhematologic malignancy marrow stimulation
Infection as cause of neutrophilia
Acute bacterial infection –> modest leukocytosis with LEFT SHIFT (most commonly band forms; severe stress –> circulating metamyelocytes)
Leukocytosis within minutes to hours - release from marrow and marginated pools
Peripheral smear: toxic granulation, Dohle bodies, cytoplasmic vacuoles
C. diff or TB cause WBC >30,000 and may result in leukemia reaction (>50,000 with a pronounced LEFT SHIFT)
Chronic inflammation as cause of neutrophilia
Increased neutrophil and monocyte rather than altered neutrophil distribution; more modest than in acute infection or inflammation
Mature neutrophil pools depleted, myeloid compartment of marrow expands
Cytokines stimulating marrow: TNFa, G-CSF, GM-CSF, MIP1, IL1, IL6, IL8
Associated with juvenile RA, RA, Still dz, Crohn dz, UC, granulomatous infection, chronic hepatitis
Cigarette smoking as cause of neutrophilia
Leukocytosis and neutrophilia in 25-50% chronic smokers
persists up to 5 year after quitting
Slows neutrophil apoptosis
Stress as cause of neutrophilia
Exercise, surgery, stress –> elevated circulating neutrophils (effects of catecholamines on marginated neutrophils)
Prevent with pre-tx with B-adrenergic antagonists (propranolol)
-exercise-induced not blocked by propranolol - flow and mechanical perturbation of neutrophils in lungs
Acute MI cause elevated WBC
Drug induced neutrophilia
Corticosteroids, B-agonists, Lithium
Lithium increases endogenous CSF production
G-CSF and GM-CSF tx can cause pronounced neutrophilic if not monitored
Nonhematologic malignancy as cause of neutrophilia
Lung, tongue, kidney, bladder tumors secrete G-CSF
Lung, stomach, breast CA met to bone and marrow causing leukoerythroblastic reaction (Left shift leukocytosis, thormbocytosis, nucleated and teardrop-shaped RBCs)
Myelophthisis - nonhematopoietic invading marrow - met CA, fibrosis, granulomatous dz
Marrow Stimulation as cause of neutrophilia
Hemolytic anemia and idiopathic thrombocytopenia purpura can stimulate marrow –> spill over leukocytosis
Recovery of cell counts following marrow suppression (chemo) –> rebound leukocytosis lasting several weeks
Hereditary Neutrophilia
AD
WBC 20,000 - 100,000/uL
Splenomegaly, widened dipolen of skull
Neutrophils functionally normal, no increased risk for bacterial infections
GCSF3 gene mutation - activation of G-CSF receptor
Chronic Idiopathic Neutrophilia
leukocytosis 11,000 - 40,000/uL with normal marrow bx
no medical sequelae
Pelter-Huet Anomaly
Mature, normal functioning neutrophils misinterpreted as band forms - raise suspicion of acute infection or inflammatory process
Mutation of lamin B receptor gene
condensed, clumped chromatin with bilobed nucleus
Pseudo - PHA:
Drug induced - reversible: colchicine, sulfonamides, Ibu, taxis, valproate
See in myelodysplasia
Vit B12 or folate deficiency increases nuclear lobation - mask PHA, PHA returns with correction of vit. deficiency
Down Syndrome in leukocytosis
10% (and trisomy 21 mosaicism)- transient myeloproliferative disorder
Peripheral blood leukocytosis with blasts
Accumulation of megakaryoblasts in blood, liver, marrow
Resolves spontaneously in most, can progress to acute megakaryoblastic leukemia in 23-30%, additional genetic events and epigenetic changes
GATA1 gene acquired mutation in fetus - hematopoietic regulation - truncated protein
Leukocyte Adhesion Deficiency
persistent leukocytosis
defects in stimulus-dependent activation of neutrophils
recurrent infections
delayed separation of umbilical cord
loss of surface adhesion molecules
LAD-1 - absence or marked reduction of common B chain in B2-integrins –> loss of expression of leukocyte function-associated antigen 1 (LFA1) - C3bi receptor, GP150;95
–> failure to ingest/kill microbes opsonized by C3bi
LAD-2 - neutrophils lack sialyl Lewis X - L-selectin ligand on endothelial cells
Neutrophils morphologically normal - defective chemotaxis, adherence, phagocytosis
Familial Cold Urticaria
episodic fevers, leukocytosis, urticaria, rash, conjunctivitis, muscle and skin tenderness with cold exposure
rash - infiltrating neutrophils
decreased levels of C1-esterase inhibitor
Mutations of CIAS1 gene on Chr 1q
