Ampath Chats

Approach to the Neutropenic Patient

Ampath Chats
Approach to the Neutropenic Patient
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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.