Neutropenia in Adults Quiz

Neutropenia Overview

• Neutropenia is a common laboratory finding in adults and children
• Underlying causes are heterogeneous, including benign conditions, autoimmune disorders, infections, and malignancies
• Clinical labs are crucial for diagnosis, using hematology, microbiology, molecular biology/cytogenetics, and clinical chemistry

Defining Neutropenia

• Normal adult absolute neutrophil count (ANC) ranges from 1.5 to 7.0 x 10⁹/L
• Lower limit of ANC varies by patient age and race
• Neonates/infants lower limit is approximately 2.5 x 10⁹/L
• Up to 25% of African-American children/adults have ANC ranging from 1.0 to 1.5 x 10⁹/L

How Neutropenia is classified

• Most labs classify neutropenia in infants with ANC < 2.5 x 10⁹/L and in adults with ANC < 1.5 x 10⁹/L
• Stratified into mild, moderate and severe based on ANC values and clinical context
  • Mild: ANC 1.0-1.5 x 10⁹/L, general good health, usually no infection
  • Moderate: ANC 0.5-1.0 x 10⁹/L, associated disease, debilitated/malnourished, usually minimal to moderate infection risk
  • Severe: ANC < 0.5 x 10⁹/L, all clinical settings, moderate to severe infection risk

Age-Related Causes of Neutropenia

• Neonates: Infection (most common), maternal hypertension/drug treatment, maternal antibody production, constitutional disorders (e.g., cyclic neutropenia, Kostmann syndrome, Chediak-Higashi syndrome)

• Infants/Children: Infections, autoimmune neutropenia, neoplasms replacing bone marrow, idiosyncratic drug reactions, secondary autoimmune neutropenia in collagen vascular disorders, immunodeficiency disorders, megaloblastic anemia, myeloablative therapies, constitutional neutropenia disorders (rare), copper deficiency (rare)

• Adults: Idiosyncratic drug reactions (most common in outpatients), infections, neoplasms replacing bone marrow, myeloablative therapies, secondary autoimmune neutropenia in collagen vascular disorders, autoimmune disorders (including white blood cell aplasia)

Classification of Neutropenia by Marrow Reserve

• Neutropenia with decreased bone marrow reserve (BM)
  • Primary: defect in granulopoiesis.
  • Secondary: suppression of normal granulopoiesis.
• Neutropenia with normal bone marrow reserve Different disorders responsible for severe congenital neutropenia have distinctive symptoms e.g., Schwachman-Diamond syndrome characterised by steatorrhea, short stature, and exocrine pancreatic deficiency

Classification of Neutropenias by Marrow Reserve and Clinical Features

• Table showing primary disorders, clinical traits, and diagnostic tools, distinguishing syndromes through characteristics and diagnostic tests

Cyclic Neutropenia, Chediak-Higashi Syndrome

• Cyclic neutropenia: Periodic apoptosis of precursors, often associated with ELA2 mutation; recurrent fever, skin/otolaryngeal infections, and no increased risk of hematological malignancies
• Chediak-Higashi syndrome: Mutation in the LYST gene, recurrent pyogenic infections, oculocutaneous albinism, decreased microbicidal activity (giant granules in cells)

Secondary Neutropenias

• Large granular lymphocytic leukaemia and related disorders
• Chemotherapy
• Drug-induced (non-immune)
• Nutritional deficiencies (protein-calorie malnutrition, folate/copper/B12 deficiency)
• Infections (viral like EBV,CMV, HIV, Hepatitis)

Neutropenia with Normal Bone Marrow Reserve

• Chronic/ benign neutropenia of infancy/childhood: Caused by antineutrophil antibodies
• Non immune chronic benign neutropenia: High incidence, increased apoptosis.
• Ethnic or Benign familial neutropenia: Unknown cause (unknown mechanism), incidence AD, findings mostly in family members (similar findings).

Alloimmune Neutropenia

• Maternal alloimmunization to HNA antigens (1a/1b/2a/1c/3a/4a)
• Moderate/severe neutropenia in newborns, cutaneous infections, UTIs, omphalitis

Drug-Induced Neutropenia

• Antibody or complement-mediated suppression of myelopoiesis
• Fever, sepsis, pneumonia, up to 50% mortality, 80% recovery rate

Infection-Related Neutropenia, Hypersplenism

• Virus-mediated antibody
• Sequestration, destruction

Diagnostic Approach to Neutropenia

• Detailed clinical history and physical examination first.
• Radiographic findings can be important
• Blood counts, Peripheral blood smear, Immunological testing, infectious disease testing, bone marrow biopsy
• Different approaches are used for children vs adults

Work-up for Pediatric and Adult Patients

• Flowcharts for evaluation and diagnostic approach, using clinical findings and lab values to guide further investigations (e.g. genetic syndromes, bone marrow biopsy)