PATHCHAT Edition No. 43
Please contact your local Ampath pathologist for more information.
Author: Dr. Rita Govender
Definition & Classification of Neutropenia
Normal absolute neutrophil count (ANC) in adults: 1.5 – 7 × 10⁹/L
Neutropenia is classified by severity:
✔ Mild Neutropenia (ANC 1.0 – 1.5 × 10⁹/L):
- Does not impair host defense.
✔ Moderate Neutropenia (ANC 0.5 – 1.0 × 10⁹/L):
- Mildly increased risk of infection, especially if immune system is compromised.
✔ Severe Neutropenia (ANC <0.5 × 10⁹/L):
- Significant infection risk.
- Increased susceptibility to opportunistic infections.
✔ Agranulocytosis (ANC <0.2 × 10⁹/L):
- Life-threatening risk of severe infections.
📌 The approach to evaluation and intervention depends on the duration, severity, and clinical presentation of neutropenia.
Causes of Neutropenia & Their Distinguishing Features
🔹 Congenital Neutropenia:
✔ Benign Ethnic Neutropenia:
- Common in African and Mediterranean populations.
- ANC >1.0 × 10⁹/L with no history of recurrent infections.
- Extensive investigations are unnecessary in asymptomatic individuals.
✔ Benign Familial Neutropenia:
- Hereditary condition without ethnic predilection.
- Similar features to benign ethnic neutropenia.
✔ Severe Congenital Neutropenia (SCN):
- Presents in infancy with agranulocytosis and recurrent infections.
- Autosomal dominant form: Selective myeloid impairment.
- Autosomal recessive form: Multi-organ involvement (neurological, cardiac, urogenital defects).
- 10–30% risk of transformation to myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML).
✔ Cyclic Neutropenia (CyN):
- Neutropenia fluctuates every 2–5 weeks.
- Mild cases are asymptomatic but may develop infections or oral ulcers during nadir.
- No increased risk of haematological malignancies.
✔ Other Congenital Syndromes:
- Fanconi Anaemia.
- Dyskeratosis Congenita.
- Myelokathexis.
- Chediak-Higashi Syndrome.
🔹 Acquired Neutropenia:
✔ Post-Infectious Neutropenia:
- Most common cause in children after viral infections.
- Bacterial causes include Mycobacteria, Rickettsia, and Brucella.
- Severe sepsis from any pathogen can deplete bone marrow reserves, leading to profound neutropenia.
✔ Drug- and Toxin-Induced Neutropenia:
- Comprehensive review of medications, herbal supplements, and occupational exposures required.
- Dose-related neutropenia is usually mild and self-limited.
- Agranulocytosis (ANC <0.2 × 10⁹/L) presents as an acute febrile illness and requires immediate drug cessation.
✔ Dietary Deficiencies:
- Severe malnutrition.
- Vitamin B12, folate, and copper deficiency.
✔ Neonatal Alloimmune Neutropenia:
- Transient neutropenia due to maternal-fetal neutrophil antigen incompatibility.
- Usually resolves within 6 weeks but can persist up to 6 months.
✔ Chronic Autoimmune Neutropenia of Infancy & Early Childhood:
- Moderate to severe neutropenia detected during febrile illnesses.
- No associated autoimmune disease or congenital syndrome.
- Resolves by 3–5 years.
✔ Felty’s Syndrome:
- Triad of rheumatoid arthritis, splenomegaly, and neutropenia.
✔ Large Granular Lymphocytic (LGL) Leukaemia:
- Associated with rheumatoid arthritis or occurs as an isolated entity.
- Characterized by a clonal population of large granular lymphocytes (>0.5 × 10⁹/L) expressing activated T-cell or NK-cell markers.
✔ Chronic Idiopathic Neutropenia (CIN):
- Discovered in adulthood, persisting for >3 months.
- Diagnosis of exclusion.
- Mild, moderate, or severe with recurrent infections in severe cases.
✔ HIV-Associated Neutropenia:
- Occurs in 10–50% of HIV-positive patients.
- Risk increases with advancing disease and ART therapy.
Management of Neutropenia
🚨 Febrile Neutropenia = Medical Emergency
✅ Definition:
- Oral temperature >38.5°C OR ≥38°C for 2 hours AND ANC <0.5 × 10⁹/L or expected to fall below 0.5 × 10⁹/L.
✅ Immediate Action: - Rapid initiation of broad-spectrum antibiotics.
- Multidisciplinary care involving a microbiologist and haematologist.
- Monitor temperature and cardiovascular parameters.
- Obtain blood cultures (peripheral and central line), urine, sputum, and stool cultures.
🔹 Stable Outpatients with Mild Neutropenia:
- Can be investigated as outpatients.
🔹 Full History & Examination:
✅ Assess for constitutional symptoms and systemic involvement.
✅ Review medication and toxin exposure (herbal, occupational, homeopathic).
✅ Check for frequent or severe infections (hospital admissions, antibiotic use).
✅ Examine for lymphadenopathy, hepatosplenomegaly, and bone pain.
🔹 Laboratory Investigations:
✅ Full Blood Count (FBC) – Minimum of 3 tests over 3 months to assess severity & duration.
✅ Peripheral Smear – Check for dysplastic changes, blasts, left shift.
✅ Cyclic Neutropenia – FBC 3× weekly for 4–6 weeks.
✅ HIV, ANA, Rheumatoid Factor, Vitamin B12, Folate.
✅ Bone Marrow Biopsy & Cytogenetics – If indicated.
Role of Granulocyte Colony-Stimulating Factor (G-CSF)
✅ Indications for G-CSF Therapy:
- History of recurrent infections.
- Severe mucosal erosions or skin infections.
- Start at 0.5–3 µg/kg daily, adjusting to the lowest effective dose.
📌 Patients requiring >8 µg/kg daily in congenital neutropenia have a higher risk of developing AML.
Key Takeaways for Clinicians
✅ Neutropenia classification is based on severity and duration.
✅ Causes range from benign ethnic variants to life-threatening conditions.
✅ Febrile neutropenia requires immediate broad-spectrum antibiotics.
✅ Investigations should be guided by clinical findings, FBC trends, and systemic involvement.
✅ G-CSF should be used selectively in high-risk patients with recurrent or severe infections.
📌 Multidisciplinary collaboration is key for effective neutropenia management.