63 Neutropenia and Neutrophilia Flashcards
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.
2 standard deviations (SDs)
Agranulocytosis indicate severe neutropenia, that is, counts less than _________
0.5 × 109/L
For children from 1 month to 10 years old, neutropenia is defined as a blood neutrophil count _____________
less than 1.5 × 109/L.
For individuals older than age 10 years, neutropenia is defined as a count _____________
less than approximately 1.8 × 109/L
In persons of African descent, neutropenia is associated with what blood type
Duffy null phenotype
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.
less than 0.5 × 109/L
General mechanisms of neutropenia
(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
The most frequent cause of neutropenia
Cytotoxic drugs
Neutropenia is caused by mutations in the HAX-1 gene
Kostmann syndrome
- Mutations lead to accelerated apoptosis of myeloid cells, as well as neurologic abnormalities.
The majority of patients with sporadic or autosomal dominant severe congenital neutropenia have heterozygous mutations of the gene for _________________
Neutrophil elastase (also called ELANE)
Patients with ELANE mutations who demonstrate a clear maturation arrest at the level of _______________
Promyelocytes
TRUE OR FALSE
Most G-CSF receptor mutations are acquired as part of the evolution to myelodysplasia or acute myelogenous leukemia.
TRUE
Most G-CSF receptor mutations are acquired as part of the evolution to myelodysplasia or acute myelogenous leukemia.
A very effective therapy for all of the recognized subtypes of severe congenital neutropenia, increasing the neutrophil counts and reducing recurrent fevers and infections
G-CSF
***Approximately 5% of patients do not respond to G-CSF.
G-CSF acts to increase the neutrophil counts by enhancing expression of a critical transcription factor for granulopoiesis ______
C/EBPβ (CCAAT/enhancer binding protein β)
Aside from GCSF, the only other therapy known to improve the clinical course of congenital neutropenia
Hematopoietic transplantation
TRUE OR FALSE
G-CSF therapy is effective in most patients with neutropenia associated with immunodeficiency syndromes
TRUE
G-CSF therapy is effective in most patients with neutropenia associated with immunodeficiency syndromes
TRUE OR FALSE
In acquired disorders neutropenia in neonates of hypertensive mothers, the presence of neutropenia is a strong negative predictor for sepsis
FALSE
In acquired disorders neutropenia in neonates of hypertensive mothers, the ABSENCE of neutropenia is a strong negative predictor for sepsis
Nutritional Deficiencies causing neutropenia
Cobalamin or Folate deficiency
Copper deficiency
A rare acquired disorder causing severe selective neutropenia.
Pure white cell aplasia
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.
Chronic Idiopathic Neutropenia in Adults
The greatest concern in Chronic Idiopathic Neutropenia
Evolution to lymphoid malignancies
Antigens with the clearest associations of autoantibodies and neutropenia
NA-1 and NA-2 (FcγRIII or CD16)
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.
Alloimmune Neonatal Neutropenia
Alloimmune Neonatal Neutropenia usually lasts _________ until the passively acquired antibody is lost
2–4 months
The diagnosis of alloimmune neutropenia usually is made using ___________
neutrophil agglutination or immunofluorescence tests
TRUE OR FALSE
In Autoimmune Neutropenia, daily or alternate-day G-CSF is effective but should be reserved for patients with recurrent infections.
TRUE
In Autoimmune Neutropenia, daily or alternate-day G-CSF is effective but should be reserved for patients with recurrent infections.
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.
50%
Triad of Felty syndrome
Splenomegaly
Deforming rheumatoid arthritis
Leukopenia
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 _________________
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.
Diseases associated with splenomegaly and neutropenia
Sarcoidosis, lymphoma, tuberculosis, malaria, kala azar, and Gaucher disease
Prototype drugs that dose-related toxicity and neutropenia
Phenothiazines, antithyroid drugs, chloramphenicol, and clozapine
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.
4–7 days
TRUE OR FALSE
In drug-induced neutropenia, an increase in the blood monocyte count heralds marrow recovery, and an “overshoot” with marked neutrophilia follows
TRUE
In drug-induced neutropenia, an increase in the blood monocyte count heralds marrow recovery, and an “overshoot” with marked neutrophilia follows
Certain viral infections, such as ________________________, may cause severe or protracted neutropenia and pancytopenia resulting from infection of hematopoietic precursor cells.
Infectious mononucleosis, infectious hepatitis, Kawasaki disease, and HIV infection
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 ________
7.5 × 109/L
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
FALSE
At birth, the mean neutrophil count is 12 × 109/L, and counts as high as 26 × 109/L are regarded as NORMAL
In normal individuals, the neutrophil count follows a diurnal pattern of variation, with peak counts in the______________
Late afternoon
Neutrophil counts also rise slightly after meals, with erect posture, and with emotional stimuli.
Mechanism of neutrophilia in CML
Increase proliferation + Increase Granulocyte survival
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
Pseudoneutrophilia (Demargination)
Demargination is dependent partially on release of neutrophils from what organs
Lungs and spleen
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
The marrow reserve pool consists principally of _______________.
Segmented neutrophils and bands
TRUE OR FALSE
Metamyelocytes are not released to the blood except under extreme circumstances.
TRUE
Metamyelocytes are not released to the blood except under extreme circumstances.
Disorder wherein neutrophils do not adhere to the capillary endothelium normally, but cell production and marrow release apparently are normal.
Leukocyte adhesion deficiency
The most frequent causes of acute neutrophilia
Exercise, Emotional stress
Any other circumstance that raises endogenous epinephrine, norepinephrine, or cortisol levels.
Bacterial infections that have an insidious onset and cause splenomegaly that characteristically do not show neutrophilia except in the initial or disseminated phase
Typhoid fever and brucellosis
Most frequent chronic noninfectious conditions causing neutrophilia
Cigarette smoking
An unusual dermatologic condition manifested as intense neutrophil accumulation in the skin and persistent neutrophilia.
Sweet syndrome
TRUE OR FALSE
Neutrophilia is usual in brain tumors, melanoma, prostate cancer, and lymphocytic malignancies.
FALSE
Neutrophilia is UNUSUAL in brain tumors, melanoma, prostate cancer, and lymphocytic malignancies.
MBLP
Neutrophilia in response to drugs is uncommon except for what drugs:
Epinephrine
Other catecholamines
Glucocorticoids
Lithium salts
Neutrophilia in Down Syndrome is caused by
Chromosome 21 trisomy and mutations in GATA1
Can be a useful screening test in cases of moderate neutrophilia (15–25 × 109/L)
Leukocyte alkaline phosphatase activity
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.
TRUE OR FALSE
Serum cobalamin levels and B12-binding proteins are elevated in both benign neutrophilia and chronic myelogenous leukemia.
TRUE
Serum cobalamin levels and B12-binding proteins are elevated in both benign neutrophilia and chronic myelogenous leukemia.
TRUE OR FALSE
In myeloproliferative neoplasms, neutrophilia is a predictor of thrombotic events
TRUE
In myeloproliferative neoplasms, neutrophilia is a predictor of thrombotic events
TRUE OR FALSE
In patients with sickle cell disease, neutrophilia correlates with increased complications and severity of the disease.
TRUE
In patients with sickle cell disease, neutrophilia correlates with increased complications and severity of the disease.
Chronic idiopathic (symptomatic) neutropenia often is associated with _____________in children.
Pyoderma and otitis media
Process where neutrophils release histones, DNA, proteases, and antimicrobial molecules that form neutrophil extracellular traps (NETs) as part of their inflammatory response.
NETOSIS
Symptoms of patients with drug-induced neutropenia
Usually present with fever, myalgia, and sore throat but usually no rash or evidence of allergy elsewhere
Ethnic groups with lower mean neutrophil counts
Africans, African Americans, and Yemenite Jews
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).
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).
Referred to as the relative abundance of early neutrophil precursors and a paucity of late-maturing cells
“Maturation arrest”
Gene mutation in the only X-linked Severe congenital neutropenia
WAS
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.
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.
