Leukocytopenias. -lymphocytopenia. -neutropenia. -monocytopenia. BHS seminar 8Nov2014
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1 Leukocytopenias -lymphocytopenia -monocytopenia -neutropenia BHS seminar 8Nov Universitair Ziekenhuis Gent Prof.dr.Lucien Noens, Hematology and Bloodbank, Ghent University hospital
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3 Neutrophil extracellular traps (NETs) and infection-related vascular dysfunction Cross-talk between infectious agents, neutrophils and platelets. Bacterial stimuli including endotoxin, lipopolysaccharide (LPS) and staphylococcal superantigen-like (SSL) proteins act on neutrophils and platelets, with released neutrophil extracell.ular traps.. Blood Reviews, Volume 26, Issue 6, 2012, Elizabeth E. Gardiner, Robert K. Andrews
4 ANC! Source: UpToDate
5 Risk of infection for different durations of neutropenia. Straka C et al. Blood 2004;104:
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7 Source: UpToDate
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9 Time is a predictive variable of utmost importance! Source: UpToDate
10 CLASSIFICATION OF NEUTROPENIAS ETIOLOGY Intrinsic defects in myeloid precursor cells Aplastic anemia Chronic idiopathic neutropenia, including benign (ethnic!) Cyclic neutropenia Associated with dysgammaglobulinemia or MDS PNH Severe congenital neutropenia (Kostmann syndrome) Secondary neutropenias Syndrome associated neutropenias* Alcoholism cartilage-hair hypoplasia Dyskeratosis congenita Glycogen storage IB Shwachman-Diamond Autoimmune, including secondary in AIDS and Felty syndrome BM replacement, MF, Cytotoxic chemotherapy or radiation therapy Drug-induced neutropenia** Agranulocytosis Mild neutropenia Folate or vitamin B12 deficiency, Copper deficiency, anorexia nervosa, caloric malnutrition Hypersplenism Infection (sepsis, viral infection) T-gamma lymphoproliferative disease, LGL-associated
11 Synopsis of cytopenias in PID. Conceptual overview, excluding primary defects of phagocyte number or function, inherited non-pid bone marrow failure syndromes, and disorders of isolated lymphopenia (without other cytopenia). *Includes hypomorphic mutations... Seidel M G Blood 2014;124:
12 Neutropenia associated ID Antineutrophil antibodies mediate destruction By splenic sequestration of opsonized cells By complement-mediated cell lysis Antineutrophil antibodies Infections Drug exposure Immune deficiencies Specific Primary immune disorders Propensity to infections more related to the underlying immune disorder Vasculitis, leading to mucosal ulcers Oral symptoms resolve with treatment of the vasculitis, with no change in the ANC, proving that the symptoms and the neutropenia are not related
13 Nutritional neutropenia Vit B 12 and folate deficiency, or inborn errors of B12 metabolism Best detected by measuring mehylmalonic acid (MMA) and homocysteine (HcY): both elevated with B12 defic, and HcY alone with folate defic Copper deficiency and subsequent low ceruloplasmin Malabsorption syndromes Post-gastric bypass surgery Critically ill patients with prolonged hospitalisations
14 Isolated neutropenia-1 Isoimmune neonatal neutropenia : FNAIN Transplacental passage of maternal anti-hna antibodies against paternal HNA Chronic Autoimmune neutropenia : Benign Neutropenia of Infancy and Childhood, with common spontaneuos remission with disappearance of autoantobodies Chronic Idiopathic neutropenia : Benign course, normal marrow reserve, antibody production in only 30-40% of cases
15 Isolated neutropenia-2 Test for collagen vascular disease and nutritional disorders first, prior to marrow examinations ANF and complement ANA Ig and immune evaluation Screen for HIV infection MMA and HcY Serum copper and ceruloplasmin
16 Infections Acquired neutropenias Drugs Immune disorders
17 Infectious neutropenias Most common cause of acquired isolated neutropenia Bacterial, viral, parasitic and rickettsial infections Short duration rarely results in bact. superinfections Mechanisms Redistribution Sequestration and aggregation Destruction by circulating Ab More severe and protracted neutropenia HBV EBV HIV
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20 Algorithm for the evaluation and treatment of adult patients with neutropenia. Gibson C, and Berliner N Blood 2014;124:
21 Source: UpToDate
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