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Questions and Answers
What is the most common cause of neutropenia in ambulatory adults?
What is the most common cause of neutropenia in ambulatory adults?
Which condition is a rare cause of neutropenia?
Which condition is a rare cause of neutropenia?
What percentage of total body neutrophils are typically circulating in the blood?
What percentage of total body neutrophils are typically circulating in the blood?
Which mechanism can lead to neutropenia by disrupting neutrophil maturation?
Which mechanism can lead to neutropenia by disrupting neutrophil maturation?
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Which type of therapy is commonly associated with neutropenia due to myeloablation?
Which type of therapy is commonly associated with neutropenia due to myeloablation?
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Which type of neutropenia is characterized by a defect in the stem cell/maturing granulocyte/storage pool phases?
Which type of neutropenia is characterized by a defect in the stem cell/maturing granulocyte/storage pool phases?
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What genetic inheritance pattern is associated with Sever congenital neutropenia?
What genetic inheritance pattern is associated with Sever congenital neutropenia?
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Which of the following is a common clinical characteristic of neutropenia with decreased BM reserve?
Which of the following is a common clinical characteristic of neutropenia with decreased BM reserve?
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Which disorder is a variant of primary neutropenia that is associated with mutations in ELA2?
Which disorder is a variant of primary neutropenia that is associated with mutations in ELA2?
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What is a potential outcome for individuals with Sever congenital neutropenia?
What is a potential outcome for individuals with Sever congenital neutropenia?
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What is the upper limit of the normal absolute neutrophil count (ANC) for adults?
What is the upper limit of the normal absolute neutrophil count (ANC) for adults?
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Which of the following is NOT a common age-related cause of neutropenia in neonates?
Which of the following is NOT a common age-related cause of neutropenia in neonates?
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What is a significant factor that can affect the lower limit of normal ANC in African American individuals?
What is a significant factor that can affect the lower limit of normal ANC in African American individuals?
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In infants, what ANC value is typically used to define neutropenia?
In infants, what ANC value is typically used to define neutropenia?
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Which of these is considered a secondary cause of neutropenia?
Which of these is considered a secondary cause of neutropenia?
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What is the typical classification system used for neutropenia based on?
What is the typical classification system used for neutropenia based on?
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Which of the following individuals is likely to have a normal ANC that can vary from 1.0 to 1.5 × 10^9/L?
Which of the following individuals is likely to have a normal ANC that can vary from 1.0 to 1.5 × 10^9/L?
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What percentage of African American children/adults typically have an ANC that ranges from 1.0 to 1.5 × 10^9/L?
What percentage of African American children/adults typically have an ANC that ranges from 1.0 to 1.5 × 10^9/L?
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What is the genetic inheritance pattern associated with Shwachman-Diamond syndrome?
What is the genetic inheritance pattern associated with Shwachman-Diamond syndrome?
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What key feature is associated with Chediac-Higashi syndrome?
What key feature is associated with Chediac-Higashi syndrome?
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What type of mutation is commonly involved in cyclic neutropenia?
What type of mutation is commonly involved in cyclic neutropenia?
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Which of the following conditions is characterized by recurrent pyogenic infections due to impaired microbicide activity?
Which of the following conditions is characterized by recurrent pyogenic infections due to impaired microbicide activity?
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In patients with drug-induced suppression of myelopoiesis, which group is most likely affected?
In patients with drug-induced suppression of myelopoiesis, which group is most likely affected?
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What percentage of patients with T-cell large granular lymphocytic leukemia may experience neutropenia?
What percentage of patients with T-cell large granular lymphocytic leukemia may experience neutropenia?
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What is a noted consequence of severe congenital neutropenia in terms of bone marrow morphology?
What is a noted consequence of severe congenital neutropenia in terms of bone marrow morphology?
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What is considered a common clinical characteristic of cyclic neutropenia?
What is considered a common clinical characteristic of cyclic neutropenia?
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Which nutritional deficiency can lead to ineffective hematopoiesis, as indicated in the content?
Which nutritional deficiency can lead to ineffective hematopoiesis, as indicated in the content?
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What type of infections are common in patients undergoing chemotherapy due to direct toxicity to neutrophils?
What type of infections are common in patients undergoing chemotherapy due to direct toxicity to neutrophils?
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What is a common infectious cause of neutropenia?
What is a common infectious cause of neutropenia?
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Which condition is associated with mild neutropenia and is not universally identifiable?
Which condition is associated with mild neutropenia and is not universally identifiable?
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Which factor is least likely to contribute to neutropenia in a neonate?
Which factor is least likely to contribute to neutropenia in a neonate?
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In the evaluation of severe neutropenia, what is considered a crucial aspect?
In the evaluation of severe neutropenia, what is considered a crucial aspect?
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Which characteristic is typical of neutropenia with normal bone marrow reserve?
Which characteristic is typical of neutropenia with normal bone marrow reserve?
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What is the most frequently detected condition before the age of 2 in neutropenic patients?
What is the most frequently detected condition before the age of 2 in neutropenic patients?
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Which virus is directly associated with immune-mediated neutropenia?
Which virus is directly associated with immune-mediated neutropenia?
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What is 'maturation arrest' in the context of neutropenia?
What is 'maturation arrest' in the context of neutropenia?
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Flashcards
Neutropenia Causes
Neutropenia Causes
Decreased neutrophils can arise from infection, drugs, and neoplasms.
Myeloablative Therapies
Myeloablative Therapies
Treatments that destroy bone marrow function, leading to neutropenia.
Normal Granulocyte Maturation
Normal Granulocyte Maturation
Neutrophils develop from stem cells in bone marrow before entering blood.
Bone Marrow Reserve
Bone Marrow Reserve
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Idiosyncratic Drug Reactions
Idiosyncratic Drug Reactions
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Neutropenia
Neutropenia
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Types of Neutropenia
Types of Neutropenia
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Primary Neutropenia
Primary Neutropenia
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Kostmann Syndrome
Kostmann Syndrome
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Secondary Neutropenia
Secondary Neutropenia
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Normal ANC Range
Normal ANC Range
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Classification of Neutropenia
Classification of Neutropenia
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Age-Related Neutropenia Causes
Age-Related Neutropenia Causes
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Causes of Neutropenia in Neonates
Causes of Neutropenia in Neonates
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Common Infection in Childhood Neutropenia
Common Infection in Childhood Neutropenia
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Primary Causes of Neutropenia
Primary Causes of Neutropenia
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Role of the Laboratory in Neutropenia
Role of the Laboratory in Neutropenia
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Myelopoiesis
Myelopoiesis
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B12 Deficiency
B12 Deficiency
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Viral Infection Neutropenia
Viral Infection Neutropenia
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Clinical History in Neutropenia
Clinical History in Neutropenia
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Congenital Neutropenia
Congenital Neutropenia
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Myelokathexis
Myelokathexis
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Antenatal Care Importance
Antenatal Care Importance
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Maturation Arrest in Myeloid Lineage
Maturation Arrest in Myeloid Lineage
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Granulocyte
Granulocyte
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Shwachman-Diamond Syndrome
Shwachman-Diamond Syndrome
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Cyclic Neutropenia
Cyclic Neutropenia
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Chediak-Higashi Syndrome
Chediak-Higashi Syndrome
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ELANE Mutation
ELANE Mutation
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Neutropenia and Infections
Neutropenia and Infections
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Drug-Induced Neutropenia
Drug-Induced Neutropenia
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Maturation Arrest in Neutrophils
Maturation Arrest in Neutrophils
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Bone Marrow Biopsy
Bone Marrow Biopsy
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Lymphocyte Proliferation
Lymphocyte Proliferation
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Study Notes
Neutropenia Overview
- Neutropenia is a common lab finding in adults and children
- Underlying causes are diverse and range from benign conditions to autoimmune disorders, infections, and malignancies
- Clinical labs play a crucial role in diagnosis through hematology, microbiology, molecular biology, cytogenetics, and clinical chemistry
- The goal of the review is to describe clinical, hematologic, and molecular genetic features of important entities causing neutropenia
- An algorithm for classifying neutropenia is also outlined.
Defining Neutropenia
- Normal absolute neutrophil count (ANC) in adults ranges from 1.5 to 7.0 x 109/L
- The lower limit of normal ANC varies by patient age and race.
- In neonates and infants, the lower limit of normal ANC is approximately 2.5 x 109/L.
- In approximately 25% of African American children & adults, ANC ranges from 1.0 to 1.5 x 109/L. Awareness of ethnic variations is crucial to avoid unnecessary testing.
- Most labs define neutropenia in infants as ANC < 2.5 x 109/L and in adults as ANC < 1.5 x 109/L.
Classifying Neutropenia
- Neutropenia is categorized into three levels based on absolute neutrophil count (ANC):
- Mild: ANC of 1.0-1.5 x 109/L, typically with general good health. Low risk of infection.
- Moderate: ANC of 0.5-1.0 x 109/L, potentially with associated diseases, debilitation, or malnutrition. Risk of infection may be minimal to moderate.
- Severe: ANC < 0.5 x 109/L, frequently associated with all clinical settings. High risk of infection.
Age-Related Causes
- Neonates: Infections are the most common cause. Also, maternal hypertension, drug treatments, or maternal antibodies.
- Infants/Children: Infections, autoimmune neutropenia, bone marrow replacement by neoplasms, idiosyncratic drug reactions, secondary immune neutropenia in collagen vascular disorders, immunodeficiency disorders, megaloblastic anemia, myeloablative therapies, constitutional neutropenia disorders, copper deficiency.
- Adults: Idiosyncratic drug reactions (most common), infections, bone marrow replacement by neoplasms, myeloablative therapies, secondary autoimmune neutropenia in collagen vascular disorders, and autoimmune disorders including white blood cell aplasia.
Neutropenia Classification by Bone Marrow Reserve
- Neutropenia due to stem cell/maturing granulocyte/storage pool defects is classified as:
- Decreased BM reserve:
- Primary: defects in granulopoiesis
- Secondary: suppression of normal granulopoiesis
- Normal BM reserve:
- Decreased BM reserve:
Congenital Neutropenias (Primary)
- Severity congenital neutropenia/Kostmann syndrome:
- Mechanism: apoptosis of precursor cells, mutations in ELA2 gene
- Inheritance: autosomal recessive (AR), autosomal dominant (AD), X-linked
- Frequency: 1-2 per million
- Clinical features: severe neutropenia in newborns, ~2% progress to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML)
- Diagnostic features: bone marrow (BM) showing promyelocyte and myelocyte arrest.
- Shwachman-Diamond syndrome:
- Mechanism: fas-mediated granulocyte apoptosis, defective SBDS gene mutation
- Inheritance: AR
- Frequency: extremely rare
- Clinical features: infections, steatorrhea, exocrine pancreatic deficiency, and ~33% progress to MDS/AML. Short stature -Diagnostic features: normal sweat chloride, increase in fecal fat.
Other congenital conditions
- Myelokathexis/neutropenia with tetraploid nuclei, reticular dysgenesis, and dyskeratosis congenita are associated with mild neutropenia.
Secondary Neutropenias
- Large granular lymphocytic leukemia and related disorders: Increased apoptosis due to FAS ligand.
- Chemotherapy: Direct toxicity to neutrophils, commonly seen.
- Drug-induced (nonimmune): Direct suppression of myelopoiesis.
- Nutritional: Ineffective myelopoiesis, protein-calorie malnutrition, folate deficiency, copper deficiency
- Viral infections: Direct or immune-mediated effects. Commonly seen infections are EBV, CMV, HIV, Hepatitis, and Measles.
- Neonates with hypertensive mothers: Low birth weight with decreased neutrophils production.
- Hypersplenism: Sequestration/destruction of neutrophils, commonly in malaria.
Neutropenia Classification based on Clinical Characteristics
- Chronic benign neutropenia of infancy and childhood: Antineutrophil antibodies are common.
- Non-immune chronic benign neutropenia: Often due to increased apoptosis.
- Ethnic or benign familial neutropenia: The cause is unknown, but it's an inherited condition common to some ethnic groups.
- Autoimmune neutropenia: Associated with immunologic conditions like ITP, AIHA, SLE, and Felty syndrome. Absolute neutrophil count (ANC) is usually low.
- Alloimmune neutropenia: Maternal alloimmunization is a significant cause. Neutropenia appears typically in newborns. The condition is often characterized by moderate-to-severe neutrophil reductions and is a result of maternal antibodies reacting against fetal neutrophils. The antibodies usually resolve by 3-4 months of age.
- Drug-induced neutropenia: Antibody-mediated or complement-mediated effects, typically an uncommon cause usually after drug administration.
Diagnostic Approach to Neutropenia
- Detailed clinical history and physical examination, including radiographic imaging (when appropriate) are critical prior to laboratory testing
- The clinical lab provides valuable information, including serial complete blood counts (CBCs), peripheral blood smear review, tests for immune status, collagen vascular disorders, viral infection, and bone marrow (BM) biopsy.
Diagnostic Approach (Pediatric Population)
- Initial evaluation includes: fever, low absolute neutrophil count (ANC), and drug/toxin history.
- Diagnostic testing includes: congenital neutropenia evaluation, ethnic/family history, and genetic syndromes.
- Subsequent testing: clinical features, cell counts, and bone marrow investigations (BM biopsy, aspirate, and flow cytometry) are performed if needed.
Diagnostic Approach (Adult Population)
- Initial consideration is fever, low ANC, and drug/toxin exposure.
- Further assessment includes new onset, associated cytopenias (pancytopenia), genetic disorders, low B12/folate, and autoimmune disease.
- Subsequent testing includes: bone marrow biopsy, aspirate, and flow cytometry, relevant testing based on individual features is necessary.
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Description
This quiz explores the overview of neutropenia, a common lab finding that can indicate a range of underlying conditions. It covers the normal absolute neutrophil count (ANC), variations by age and race, and the role of clinical labs in diagnosis. Understand the clinical, hematologic, and molecular aspects of neutropenia to enhance your knowledge in this important area of health.
