63 Neutropenia and Neutrophilia

Question 1

Neutropenia refers to an absolute blood neutrophil count (total leukocyte count per microliter × percent of neutrophils) that is less than _____ standard deviations (SDs) below the normal mean of the population.

Answer 1

2 standard deviations (SDs)

Question 2

Agranulocytosis indicate severe neutropenia, that is, counts less than _________

Answer 2

0.5 × 109/L

Question 3

For children from 1 month to 10 years old, neutropenia is defined as a blood neutrophil count _____________

Answer 3

less than 1.5 × 109/L.

Question 4

For individuals older than age 10 years, neutropenia is defined as a count _____________

Answer 4

less than approximately 1.8 × 109/L

Question 5

In persons of African descent, neutropenia is associated with what blood type

Answer 5

Duffy null phenotype

Question 6

Individuals with neutrophil counts less than ___________ are at substantially greater risk, but the frequency of infections varies considerably, depending on the cause and duration of neutropenia.

Answer 6

less than 0.5 × 109/L

Question 7

General mechanisms of neutropenia

Answer 7

(a) hypoplastic neutropoiesis,
(b) ineffective neutropoiesis (resulting from exaggerated apoptosis of neutrophils or their precursors)
(c) accelerated removal or utilization of circulating neutrophils
(d) shifts of cells from the circulating to the marginal blood pools
(e) a combination of these mechanisms

Question 8

The most frequent cause of neutropenia

Answer 8

Cytotoxic drugs

Question 9

Neutropenia is caused by mutations in the HAX-1 gene

Answer 9

Kostmann syndrome

• Mutations lead to accelerated apoptosis of myeloid cells, as well as neurologic abnormalities.

Question 10

The majority of patients with sporadic or autosomal dominant severe congenital neutropenia have heterozygous mutations of the gene for _________________

Answer 10

Neutrophil elastase (also called ELANE)

Question 11

Patients with ELANE mutations who demonstrate a clear maturation arrest at the level of _______________

Answer 11

Promyelocytes

Question 12

TRUE OR FALSE

Most G-CSF receptor mutations are acquired as part of the evolution to myelodysplasia or acute myelogenous leukemia.

Answer 12

TRUE

Most G-CSF receptor mutations are acquired as part of the evolution to myelodysplasia or acute myelogenous leukemia.

Question 13

A very effective therapy for all of the recognized subtypes of severe congenital neutropenia, increasing the neutrophil counts and reducing recurrent fevers and infections

Answer 13

G-CSF

***Approximately 5% of patients do not respond to G-CSF.

Question 14

G-CSF acts to increase the neutrophil counts by enhancing expression of a critical transcription factor for granulopoiesis ______

Answer 14

C/EBPβ (CCAAT/enhancer binding protein β)

Question 15

Aside from GCSF, the only other therapy known to improve the clinical course of congenital neutropenia

Answer 15

Hematopoietic transplantation

Question 16

TRUE OR FALSE

G-CSF therapy is effective in most patients with neutropenia associated with immunodeficiency syndromes

Answer 16

TRUE

G-CSF therapy is effective in most patients with neutropenia associated with immunodeficiency syndromes

Question 17

TRUE OR FALSE

In acquired disorders neutropenia in neonates of hypertensive mothers, the presence of neutropenia is a strong negative predictor for sepsis

Answer 17

FALSE

In acquired disorders neutropenia in neonates of hypertensive mothers, the ABSENCE of neutropenia is a strong negative predictor for sepsis

Question 18

Nutritional Deficiencies causing neutropenia

Answer 18

Cobalamin or Folate deficiency
Copper deficiency

Question 19

A rare acquired disorder causing severe selective neutropenia.

Answer 19

Pure white cell aplasia

Question 20

This neutropenia is a distinct syndrome predominantly affecting young adult women ages 18–35 years; the female-to-male ratio is approximately 8 to 1.

The patients have no chromosomal abnormalities or other evidence of myelodysplasia.

Answer 20

Chronic Idiopathic Neutropenia in Adults

Question 21

The greatest concern in Chronic Idiopathic Neutropenia

Answer 21

Evolution to lymphoid malignancies

Question 22

Antigens with the clearest associations of autoantibodies and neutropenia

Answer 22

NA-1 and NA-2 (FcγRIII or CD16)

Question 23

The disorder results from transplacental passage of maternal (Ig G antibodies that bind to the infant’s neutrophil-specific antigens, usually the FcγRIIIb (HNA1 or CD16b) isotype inherited from the infant’s father.

Answer 23

Alloimmune Neonatal Neutropenia

Question 24

Alloimmune Neonatal Neutropenia usually lasts _________ until the passively acquired antibody is lost

Answer 24

2–4 months

Question 25

The diagnosis of alloimmune neutropenia usually is made using ___________

Answer 25

neutrophil agglutination or immunofluorescence tests

Question 26

TRUE OR FALSE In Autoimmune Neutropenia, daily or alternate-day G-CSF is effective but should be reserved for patients with recurrent infections.

Answer 26

TRUE In Autoimmune Neutropenia, daily or alternate-day G-CSF is effective but should be reserved for patients with recurrent infections.

Question 27

In SLE, total leukocyte counts usually are between 2 and 5 × 109/L, and neutrophils are less than 1.8 × 109/L in approximately ______ of patients with SLE.

Answer 27

50%

Question 28

Triad of Felty syndrome

Answer 28

Splenomegaly Deforming rheumatoid arthritis Leukopenia

Question 29

A subset of patients with Felty syndrome have a high blood concentration of large granular lymphocytes with a phenotype characteristic of immature natural killer cells. They respond to combinations of _________________

Answer 29

Methotrexate and G-CSF **These patients tend to respond poorly to therapies directed toward increasing neutrophil levels but may respond to combinations of methotrexate and G-CSF.

Question 30

Diseases associated with splenomegaly and neutropenia

Answer 30

Sarcoidosis, lymphoma, tuberculosis, malaria, kala azar, and Gaucher disease

Question 31

Prototype drugs that dose-related toxicity and neutropenia

Answer 31

Phenothiazines, antithyroid drugs, chloramphenicol, and clozapine

Question 32

In patients with sparse marrow neutrophils but normal-appearing precursor cells (promyelocytes and myelocytes), neutrophils reappear in the blood approximately _______days after the offending drug is stopped.

Answer 32

4–7 days

Question 33

TRUE OR FALSE In drug-induced neutropenia, an increase in the blood monocyte count heralds marrow recovery, and an “overshoot” with marked neutrophilia follows

Answer 33

TRUE In drug-induced neutropenia, an increase in the blood monocyte count heralds marrow recovery, and an “overshoot” with marked neutrophilia follows

Question 34

Certain viral infections, such as ________________________, may cause severe or protracted neutropenia and pancytopenia resulting from infection of hematopoietic precursor cells.

Answer 34

Infectious mononucleosis, infectious hepatitis, Kawasaki disease, and HIV infection

Question 35

Neutrophilia is defined as an increase in the absolute blood neutrophil count to a level greater than 2 SDs; For children age 1 month or older and adults of all ages, this level is approximately ________

Answer 35

7.5 × 109/L

Question 36

TRUE OR FALSE At birth, the mean neutrophil count is 12 × 109/L, and counts as high as 26 × 109/L are regarded as abnormal

Answer 36

FALSE At birth, the mean neutrophil count is 12 × 109/L, and counts as high as 26 × 109/L are regarded as **NORMAL**

Question 37

In normal individuals, the neutrophil count follows a diurnal pattern of variation, with peak counts in the______________

Answer 37

Late afternoon ## Footnote Neutrophil counts also rise slightly after meals, with erect posture, and with emotional stimuli.

Question 38

Mechanism of neutrophilia in CML

Answer 38

Increase proliferation + Increase Granulocyte survival

Question 39

Response caused by a shift of cells from the marginal to the circulating pool; seen in vigorous exercise and acute physical and emotional stress and mimicked by infusion of epinephrine and other catecholamines

Answer 39

Pseudoneutrophilia (Demargination)

Question 40

Demargination is dependent partially on release of neutrophils from what organs

Answer 40

Lungs and spleen ## Footnote Dependent partially on release of neutrophils from the lungs and spleen, but redistribution from other vascular beds, particularly the **pulmonary capillaries**, is quantitatively more important

Question 41

The marrow reserve pool consists principally of _______________.

Answer 41

Segmented neutrophils and bands

Question 42

TRUE OR FALSE Metamyelocytes are not released to the blood except under extreme circumstances.

Answer 42

TRUE Metamyelocytes are not released to the blood except under extreme circumstances.

Question 43

Disorder wherein neutrophils do not adhere to the capillary endothelium normally, but cell production and marrow release apparently are normal.

Answer 43

Leukocyte adhesion deficiency

Question 44

The most frequent causes of acute neutrophilia

Answer 44

Exercise, Emotional stress ## Footnote Any other circumstance that raises endogenous epinephrine, norepinephrine, or cortisol levels.

Question 45

Bacterial infections that have an insidious onset and cause **splenomegaly** that characteristically **do not show neutrophilia except in the initial or disseminated phase**

Answer 45

Typhoid fever and brucellosis

Question 46

Most frequent chronic noninfectious conditions causing neutrophilia

Answer 46

Cigarette smoking

Question 47

An unusual dermatologic condition manifested as intense neutrophil accumulation in the skin and persistent neutrophilia.

Answer 47

Sweet syndrome

Question 48

TRUE OR FALSE Neutrophilia is usual in brain tumors, melanoma, prostate cancer, and lymphocytic malignancies.

Answer 48

FALSE Neutrophilia is UNUSUAL in brain tumors, melanoma, prostate cancer, and lymphocytic malignancies. | MBLP

Question 49

Neutrophilia in response to drugs is uncommon except for what drugs:

Answer 49

Epinephrine Other catecholamines Glucocorticoids Lithium salts

Question 50

Neutrophilia in Down Syndrome is caused by

Answer 50

Chromosome 21 trisomy and mutations in GATA1

Question 51

Can be a useful screening test in cases of moderate neutrophilia (15–25 × 109/L)

Answer 51

Leukocyte alkaline phosphatase activity ## Footnote Ordinarily, the values are **elevated** with **inflammation** of any cause and in subjects receiving **glucocorticoid therapy**. The values are **low** in **chronic myelogenous leukemia** and variable with other myeloproliferative neoplasms.

Question 52

TRUE OR FALSE Serum cobalamin levels and B12-binding proteins are elevated in both benign neutrophilia and chronic myelogenous leukemia.

Answer 52

TRUE Serum cobalamin levels and B12-binding proteins are elevated in both benign neutrophilia and chronic myelogenous leukemia.

Question 53

TRUE OR FALSE In myeloproliferative neoplasms, neutrophilia is a predictor of thrombotic events

Answer 53

TRUE In myeloproliferative neoplasms, neutrophilia is a predictor of thrombotic events

Question 54

TRUE OR FALSE In patients with sickle cell disease, neutrophilia correlates with increased complications and severity of the disease.

Answer 54

TRUE In patients with sickle cell disease, neutrophilia correlates with increased complications and severity of the disease.

Question 55

Chronic idiopathic (symptomatic) neutropenia often is associated with _____________in children.

Answer 55

Pyoderma and otitis media

Question 56

Process where neutrophils release histones, DNA, proteases, and antimicrobial molecules that form neutrophil extracellular traps (NETs) as part of their inflammatory response.

Answer 56

NETOSIS

Question 57

Symptoms of patients with drug-induced neutropenia

Answer 57

Usually present with fever, myalgia, and sore throat but usually no rash or evidence of allergy elsewhere

Question 58

Ethnic groups with lower mean neutrophil counts

Answer 58

Africans, African Americans, and Yemenite Jews

Question 59

TRUE OR FALSE Severe acute neutropenia (ie, developing over a few hours or days) usually is associated with same risk of infection with severe chronic neutropenia (usually present for months or years).

Answer 59

FALSE Severe acute neutropenia (ie, developing over a few hours or days) usually is associated with **greater risk of infection** than severe chronic neutropenia (usually present for months or years).

Question 60

Referred to as the relative abundance of early neutrophil precursors and a paucity of late-maturing cells

Answer 60

“Maturation arrest”

Question 61

Gene mutation in the only X-linked Severe congenital neutropenia

Answer 61

WAS

Question 62

TRUE OR FALSE There are rare cases of biallelic mutations within the intracellular domain of the G-CSF receptor that lead to nonresponse to treatment with G-CSF.

Answer 62

FALSE There are rare cases of biallelic mutations within the **extracellular** domain of the G-CSF receptor that lead to nonresponse to treatment with G-CSF.