BL - Disorders of WBC Number

Question 1

Characteristics of monocytes/tissue macrophages

Answer 1

Shorter time in marrow (7 days). No storage. 3-5 days in intravascular compartments, then in tissues for days-months. Move to sites of infection/inflammation, filter, process and present antigens, clear apoptotic cells and debris.

Question 2

Characteristics of neutrophils

Answer 2

Produced in marrow, storage pool for host defense (10-14 days). In peripheral blood for 6 hours, then move to tissues. Turnover 1-2 days. Innate immune system: non-specific defense against microbes.
Production and kinetics: exist in compartments in marrow (stem cells, myeloid precursors). Presence of storage compartment of neutrophils (bands and segs) very different than other blood cells. Underproduction neutropenia caused by depletion of storage pool. Die by apoptosis after clearing bugs and are eaten up by macrophages.

Question 3

Characteristics of eosinophils

Answer 3

Produced in bone marrow under influence of IL-5. Bilobate nuclei. Released into peripheral blood and move to external surfaces (GI tract, tracheobronchial tree, etc.) Function as a phagocyte. Roles in allergies, parasite infection, response to tumors: immunoenhancing or immunosuppressive.

Question 4

Characteristics of basophils

Answer 4

Produced in bone marrow, released in peripheral blood, move to tissues. Have receptors for IgE. Function: pathophysiology of hypersensitivity reactions (allergic).

Question 5

Neutropenia

Answer 5

Decrease in absolute neutrophil count (include bands, segs, segmented PMNs) - reference ranges based on race, ethnicity, age. Implies a decrease in marrow myeloid pools to the extent that neutrophil delivery to infected tissues can be decreased, allowing microbes to proliferate. Moderate to severe risk of possibly septic infection when ANC/ul is <500.

Question 6

Classification of neutropenias

Answer 6

Marked decrease in bone marrow reserve (primary, secondary, complex phenotype, or other)
Normal bone marrow reserve with increase in turnover (immune or non-immune)

Question 7

Alternative classification of neutropenias

Answer 7

Congenital/primary neutropenias
Secondary neutropenias (infection, drugs/toxins, aplastic syndromes, B12/folate deficiency, hypersplenism)
Immune neutropenias

Question 8

Infection-associated neutropenia

Answer 8

Most common cause of neutropenia. Usually acute, resolves in days to months.
Possible mechanisms: increased utilization (from infection), complement mediated margination, marrow suppression/failure (direct effect), cytokine/chemokine induced margination, antibody production.
Lots of infectious agents associated: viral, bacterial, fungal, protozoal, Rickettsial.

Question 9

Secondary causes - drugs/toxins

Answer 9

Immune (ex. penicillin, other antibiotics)
Toxic (ex. phenothiazine)
Hypersensitivity (ex. Dilantin, phenobarbital)

Question 10

Other causes

Answer 10

Cancer chemotherapy (suppression myelopoiesis)
Aplastic anemia (stem cell failure)
B12/folate deficiency (ineffective hematopoiesis)
Hypersplenism (reticuloendothelial sequestration)

Often see other cytopenias in conjunction.

Question 11

Immune neutropenias

Answer 11

Antibodies to neutrophils. Marrow production: normal to increased. Storage pool: normal to slightly decreased. Increase in turnover of neutrophils; decreased in vascular compartment.
Categories: alloimmune, chronic benign neutropenia of childhood, autoimmune, drug-induced.

Question 12

Alloimmune neutropenia

Answer 12

Maternal alloimmunization to neutrophil-specific antigens, transplacental passage, binding to neonatal neutrophils

Question 13

Kostmann’s syndrome

Answer 13

Apoptosis of myeloid precursors. ELA-2 or HAX-1 gene mutations (more rarely defects in G-CSF receptor). AD/AR/S.
Presents with severe neutropenia, monocytosis, eosinophilia. Myeloid hyperplasia in marrow, severe maturation arrest in promyelocyte/myelocyte stage. Recurrent purulent infections in first few months: S. aureus, E. coli, Pseudomonas. Risk for MDS or AML.
Manage by treating infections, administering G-CSF, consider BMT.

Question 14

Cyclic neutropenia

Answer 14

ELA-2 mutations and apoptosis in precursors and cyclic hematopoiesis. AD/S.
Characterized by recurrent fever, pharyngitis, aphthous ulcers, gingivitis, periodontitis. Cycles 21 +/- 3 days with ANC <200/ul for 3-5 days.
Manage by aggressive antibiotic/supportive care for infection, G-CSF daily or alternate days.

Question 15

Schwachman-Diamond syndrome

Answer 15

FAS-associated apoptosis of marrow precursors, decreased CD34+ cells, marrow stromal defect. AR inheritance. May have defect in SBDS gene, chromosome 7.
Multisystem disease: neutropenia, pancreatic insufficiency, metaphyseal chondrodysplasia. 25% develop MDS/AML. May have associated neutrophil dysfunction; recurrent infections.
Manage with pancreatic enzyme replacement/G-CSF, aggressive antibiotic therapy and supportive care for infection. BMT in severe cases.

Question 16

Chronic idiopathic neutropenia

Answer 16

Myeloid hyperplasia and maturation arrest at myelocyte, metamyelocyte, or band stage. No specific inheritance identified (sporadic). No neutrophil antibodies detected. No other associated findings. Usually responsive to G-CSF.

Question 17

Treatment strategies for neutropenias

Answer 17

G-CSF will spur neutrophils to be produced- normalize production. May get prophylactic antibiotics.
Secondary neutropenias: stop unnecessary drugs/eliminate toxins, treat underlying disorders, replace specific deficiencies, aggressively manage infections, supportive care, G-CSF in some conditions.

Question 18

Leukocytosis

Answer 18

Increase in total WBC count

Question 19

Left shift

Answer 19

Changes in normal WBC differential characterized by an increase in neutrophils

Question 20

Eosinophilia

Answer 20

Absolute eosinophil count > 350/ul.
Causes: allergic disorders, dermatitis, parasitic/other infections, tumors, hereditary disorders, GI disorders, hypereosinophilic syndromes

Question 21

Basophilia

Answer 21

Caused by hypersensitivity reactions, inflammation/infection, myeloproliferative diseases.

Question 22

Monocytosis

Answer 22

Absolute monocyte count >500 in children, adults. Caused by hematologic disorders and lymphomas, collagen vascular disease, granulomatous disease, infection, malignant disease (carcinoma).