Agranulocytosis (Neutropenia)

Agranulocytosis (Neutropenia) – Treatment Options

Introduction
Agranulocytosis, a severe form of neutropenia, is characterized by a critically low absolute neutrophil count (ANC), usually <500 cells/µL. It can result from drug-induced bone marrow suppression (most common cause, e.g., clozapine, carbimazole, sulfonamides, chemotherapy), autoimmune destruction, infections, or bone marrow failure syndromes. Patients are at high risk of life-threatening bacterial and fungal infections, often presenting with fever, sore throat, oral ulcers, and sepsis. Prompt recognition and aggressive management are essential to reduce morbidity and mortality.

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1. Immediate Supportive Measures

• Hospitalization: All patients with febrile agranulocytosis require inpatient care.

• Protective isolation: Minimize infection exposure with strict hygiene and reverse isolation if available.

• Broad-spectrum antibiotics:

  • Empiric IV antibiotics started immediately at onset of fever, even before culture results.

  • Common regimen: antipseudomonal beta-lactam (cefepime, piperacillin-tazobactam, or meropenem).

  • Add antifungal coverage (e.g., amphotericin B, voriconazole) if fever persists beyond 4–7 days.

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2. Granulocyte Colony-Stimulating Factor (G-CSF)

• Filgrastim or lenograstim: Stimulate neutrophil production, shorten duration of neutropenia, and reduce infection risk.

• Particularly useful in drug-induced agranulocytosis or chemotherapy-related neutropenia.

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3. Identification and Removal of Underlying Cause

• Drug-induced agranulocytosis:

  • Immediate discontinuation of the offending drug (e.g., clozapine, carbimazole, dapsone).

  • Re-exposure must be strictly avoided.

• Autoimmune neutropenia:

  • May require immunosuppressive therapy (e.g., corticosteroids).

• Bone marrow disorders (aplastic anemia, leukemia):

  • Managed with disease-specific therapy.

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4. Hematopoietic Stem Cell Transplantation (HSCT)

• Considered in cases of congenital severe neutropenia or refractory aplastic anemia.

• Offers potential cure but associated with high risks.

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5. Supportive and Preventive Care

• Antimicrobial prophylaxis: Fluoroquinolones, antifungals, or antivirals in selected high-risk patients (e.g., prolonged neutropenia in chemotherapy).

• Oral care: Antiseptic mouth rinses to reduce mucosal infections.

• Vaccinations: Pneumococcal and influenza vaccines to reduce risk of secondary infections.

• Granulocyte transfusions: Rarely used in severe, refractory infections.

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6. Long-Term Monitoring

• Regular blood counts until recovery.

• Careful documentation of causative drugs for future avoidance.

• Monitoring for complications such as septic shock, pneumonia, or invasive fungal infections.