© 2010 Universitair Ziekenhuis Gent

Leukocytopenias

-lymphocytopenia

-monocytopenia

-neutropenia

BHS seminar 8Nov2014

Prof.dr.Lucien Noens, Hematology and Bloodbank,

Ghent University hospital

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..

Elizabeth E. Gardiner , Robert K. Andrews

Neutrophil extracellular traps (NETs) and infection-related vascular dysfunction

Blood Reviews, Volume 26, Issue 6, 2012, 255 - 259

ANC !

Source:UpToDate

Risk of infection for different durations of neutropenia.

Straka C et al. Blood 2004;104:1989-1994

Source:UpToDate

Time is a predictivevariable of utmost importance !

Source:UpToDate

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)

Syndrome associated neutropenias*

Secondary neutropenias Alcoholism

Autoimmune, including secondary in AIDS and Felty syndrome

BM replacement , MF, …

Cytotoxic chemotherapy or radiation therapy

Drug-induced neutropenia**

Folate or vitamin B12 deficiency, Copper deficiency, anorexia nervosa, caloric malnutrition

Hypersplenism

Infection (sepsis, viral infection)

T-gamma lymphoproliferative disease, LGL-associated

•cartilage-hair hypoplasia•Dyskeratosis congenita•Glycogen storage IB•Shwachman-Diamond

AgranulocytosisMild neutropenia

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;124:2337-2344

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 underlyingimmune 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

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 elevatedwith 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

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 disappearanceof autoantobodies

• Chronic Idiopathic neutropenia :– Benign course, normal marrow reserve, antibody

production in only 30-40% of cases

Isolated neutropenia-2

• Test for collagen vascular disease and nutritional disorders first, prior to marrowexaminations– ANF and complement

– ANA

– Ig and immune evaluation

– Screen for HIV infection

– MMA and HcY

– Serum copper and ceruloplasmin

Acquired neutropenias

• Infections

• Drugs

• Immune disorders

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

Algorithm for the evaluation and treatment of adult patients with neutropenia.

Gibson C , and Berliner N Blood 2014;124:1251-1258

Source:UpToDate