(F) L3.1 Non-malignnt WBC disorders Flashcards
causes of non-malignant WBC disorders
genetic or acquired
causes: Infection, trauma, injury, or inflammatory
responses.
● Types of Anomalies:
○ Quantitative
■ Absolute increase or decrease in
specific white blood cells in response to
stress or infection.
■ Disorder on the number of circulating cells
○ Qualitative
■ Morphological changes in white blood
cells during infections
■ Changes in the normal morphology of
circulating cells
❖ Normal morphology but abnormal
function
● These abnormalities are typically reversible once the
stressful event subsides.
STRESS/REACTIVE DISORDER
Causes: Genetic mutations leading to abnormal
appearance of white blood cells.
● Types of Changes:
○ Quantitative: Changes in the number of
leukocytes.
○ Functional: Changes in the function of
leukocytes.
○ Morphologic: Structural changes in leukocytes.
● Reversibility: These abnormalities are non-reversible.
● Severity: The severity can range from mild to severe.
GENETIC DISORDERS
types of WBC disorders
a. neutrophil
b. monocytes / macrophages
c. eosinophils
d. basophils
e. lymphocytes
f. leukopenia
- Increase during acute bacterial infections
- Increase during chronic
infections. - Decrease in WBC count.
- Increase during viral infections to help achieve lifetime immunity
- Increase during parasitic infections or larval invasions.
- Increase in certain immune responses and
allergic reactions
- A
- B
- F
4.E - C
- D
Increase in neutrophils above 7.0 × 109
/L in adults and
8.5 × 109
/L in children
● Normal Relative Count: Approximately 50% to 70%
NEUTROPHILIA
By adding the number of segmented and band neutrophils (may include metamyelocytes and
myelocytes).
Used to evaluate neutrophelia
ANC Calculation
If there is neutrophilia, there is always
a shift to the (left/right)
left
leukemoid reaction
a. parasitic infection
b. treponemal infection
a
neutropenia
associations of leukemoid reaction
infections
medications
other conditions (intoxications, hemorrhage, hemolysis, and splenectomy)
Metabolic disease and inflammation
neutropenia
what is the indicator of leukemoid reactions
toxic vacuoles in neutrophils
neutropenia
Presence of immature neutrophils nucleated red blood
cells (RBCs), and teardrop RBCs in a peripheral blood
smear.
INDICATORS
● Immature Neutrophils and Nucleated RBCs: Key
features of LER.
● Teardrop RBCs: Suggest extramedullary
hematopoiesis and myelofibrosis, especially primary
myelofibrosis.
● Neutrophilia: Often accompanies LER.
ASSOCIATIONS
● Cancers: Space-occupying metastasis, lymphoma,
leukemia, and primary myelofibrosis.
● Other Conditions: Hemolytic disorders, infections,
hemorrhage, and other conditions.
BONE MARROW INVOLVEMENT
● Space-Occupying Lesions: Metastatic tumors,
fibrosis, lymphoma, leukemia, or a marked increase in
one of the normal marrow cells.
LEUKOERYTHROBLASTIC REACTION
a. neutropenia
b. severe neutropenia
c. agranulocytosis
Decrease in the Absolute Neutrophil Count (ANC) to
less than 1.5 × 109
/L
Neutrophil count less than 0.1 ×
109
/L.
ANC less than 0.5 × 109
/L,
significantly increasing the risk of opportunistic
infections.
ACB
CAUSES OF NEUTROPENIA
- (increased / decreased) rate of removal / destruction
- (increased/decreased) production / ineffective hematopoiesis
- circulating vs marginal pool ratio
- Combination of above factors
increased
decreased
neutropenia
Caused by antibody binding to neutrophil antigens
IMMUNE-MEDIATED NEUTROPENIA
neutropenia
Cause: Maternal IgG crosses the placenta and binds to
neutrophil-specific antigens inherited from the father
(e.g., FcgRIIIb, NB1, HLA).
● Incidence: Approximately 1 in 2000 births.
● Neutrophil Count: Increases or returns to normal after
a few months as maternal antibodies decline and
disappear from the baby’s circulation.
ALLOIMMUNE NEONATAL NEUTROPENIA
neutropenia
Primarily Affects: Children.
● Cause: Development of antibodies to HNA-1.
● Severity: Moderate to severe neutropenia.
● Nature: Self-limiting
AUTOIMMUNE NEUTROPENIA
neutropenia
Associated Conditions: Autoimmune disorders such
as rheumatoid arthritis (RA), Felty syndrome, systemic
lupus erythematosus (SLE), and Sjogren syndrome.
● Other Factors: Immune complex deposition,
granulopoiesis-inhibiting cytokines, and splenomegaly
can also induce neutropenia.
SECONDARY AUTOIMMUNE NEUTROPENIA
neutropenia
● Nature: Most often an acquired condition.
● Causes: Numerous, including drug-induced
neutropenia and neonatal alloimmune neutropenia.
ACQUIRED NEUTROPENIA
neutropenia
Source: Most cases of acquired neutropenia.
● Mechanism: Due to myeloid suppression or
immunologic response.
DRUG-INDUCED NEUTROPENIA
neutropenia
2 types of acquired neutropenia
drug induced
neonatal alloimmune neutropenia
neutropenia
Mechanism: Maternal immunoglobulin G (IgG) crosses
the placenta and binds to paternal human neutrophil
antigens (HNA) on fetal leukocytes.
● Effect: Antibody-coated neutrophils are removed from
circulation, resulting in an ANC of less than 0.5 × 109
/L,
often within 1 week of birth
● Common HNAs: HNA-1 and HNA-3 (most often
implicated), HNA-2 (historically common).
● Incidence: 0.9% in the U.S. (2021).
● Infections: Usually not life-threatening.
● Recovery: ANC generally normalizes within 6 months
as maternal IgG is cleared from circulation.
NEONATAL ALLOIMMUNE NEUTROPENIA (NAN
neutropenia
NC below the age-specific reference interval and
presence of IgG autoantibodies against one or more
human neutrophil antigens (HNA).
Incidence: Approximately 1 per 100,000 children under
10 years.
● Onset: Typically manifests around 7 to 9 months.
● Symptoms: Mild infections, usually manageable with
conservative approaches.
● Treatment: Routine antibiotic prophylaxis is not
commonly used.
● Prognosis: Self-limiting, with most patients recovering
spontaneously by 4 to 5 years.
AUTOIMMUNE NEUTROPENIA (AIN)
neutropenia
Common in Adults: Associated with various conditions
and factors.
● Associated Conditions:
○ Connective tissue disorders.
○ Felty syndrome.
○ Hematopoietic neoplasms.
○ Solid tumors.
○ Primary immunodeficiencies.
○ Bacterial and viral infections.
○ Transplant.
○ Idiosyncratic reactions to medications.
● Immunologic Mechanisms:
○ Formation of immune complexes.
○ Haptens.
○ Drug-induced formation of neutrophil
autoantibodies.
○ T-lymphocyte toxicity.
AUTOIMMUNE NEUTROPENIA (AIN
causes cyclic neutropenia
ELANE mutations
Neutropenia
- Less severe than Severe Congenital Neutropenia
(SCN1), which also involves ELANE mutations - Episodes of severe neutropenia (less than 0.2 × 109
/L)
occur in approximately 21-day cycles, each lasting 3 to
5 or more days - Accompanied by absolute monocytosis
causes cyclic neutropenia
all but one is a symptom of neutropenia episodes
Mouth ulcers
● Sore throat
● Gingivitis
● Rash
● lesions
● Fatigue
● Fever
● Cervical lymphadenopathy
lesions
Cyclic neutropenia has (high / no / lower) risk of life threatening infections compared to SCN1
lower
Adult predominantly affects women 18 to 35 y.o.,
generally shows more immature neutrophils than
mature neutrophil
CHRONIC IDIOPATHIC NEUTROPENIA
EOSINOPHILIA
Increase in circulating eosinophils with an absolute
count above 0.4 × 109
/L
○ Nonmalignant causes of eosinophilia
○ Cytokine stimulation, especially from
interleukin-3 and interleukin-5 (IL3 and IL5)
EOSINOPHILIA
EOSINOPHILIA
(>1.5 × 109
/L) lasting more than 6 months without an
identifiable cause, the diagnosis is most likely;
considered myeloproliferative neoplasm
HYPEREOSINOPHILIC SYNDROME (HES)
An absolute count of basophils greater than 0.15 × 109
/L
○ The presence of a malignant myeloproliferative
neoplasm such as chronic myelogenous
leukemia
BASOPHILIA
- Absolute monocyte count greater than 1.0 × 109
/L in adults and greater than 3.5 × 109/L in neonates - First sign of recovery from acute overwhelming
infection or severe neutropenia - Most commonly after cancer chemotherapy
positive sign of recovery
MONOCYTOSIS
