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Agranulocytosis: Causes, Symptoms, and Treatment

Agranulocytosis is a severe, potentially life-threatening condition defined by an absolute neutrophil count (ANC) <500/µL (severe <100/µL). Neutrophils are essential for bacterial and fungal defense; their depletion leaves patients vulnerable to rapidly progressive infections.

Etiology

Drug-Induced (Most Common, ~70%)

  • Antithyroid drugs: Methimazole, propylthiouracil (0.1–0.5% incidence).
  • Chemotherapy: Dose-dependent myelosuppression (expected, monitored).
  • Antibiotics: Beta-lactams, TMP-SMX, chloramphenicol, dapsone.
  • Antipsychotics: Clozapine (~0.8% risk; requires REMS monitoring).
  • Others: Anticonvulsants (carbamazepine, valproate), NSAIDs, sulfasalazine, procainamide, TNF inhibitors, statins (rare).

Autoimmune

  • Primary autoimmune neutropenia (infants/children).
  • Secondary: SLE, Felty syndrome (RA + splenomegaly + neutropenia), granulomatosis with polyangiitis.

Infectious

  • Viral: EBV, CMV, HIV, hepatitis, parvovirus B19, influenza, COVID-19.
  • Bacterial: Typhoid, brucellosis, TB, sepsis (consumption).
  • Rickettsial, parasitic.

Bone Marrow Disorders

  • Aplastic anemia, MDS, leukemia, myelofibrosis, metastatic infiltration.
  • Nutritional: B12, folate, copper deficiency.

Other

  • Radiation exposure.
  • Hypersplenism (portal hypertension, storage diseases).
  • Cyclic neutropenia (ELANE mutation; 21-day cycles).

Clinical Presentation

  • Fever: Often the only sign (>38.3°C / 101°F).
  • Chills, rigors, hypotension (sepsis).
  • Mucosal ulcerations: oral, pharyngeal, perianal.
  • Skin: cellulitis, abscesses, ecthyma.
  • Pneumonia, peritonitis, UTI, bacteremia.
  • Notably: absence of pus (neutrophils needed for pus formation).

Diagnostic Workup

  1. CBC with differential → confirm ANC <500.
  2. Medication review: temporal relationship (typically 1–12 weeks after start).
  3. Peripheral smear: confirm neutropenia, rule out pseudoneutropenia, assess morphology.
  4. Bone marrow biopsy: cellularity, maturation arrest, dysplasia, infiltration (if cause unclear or persistent).
  5. Autoantibodies (antineutrophil), viral serologies, nutritional labs, flow cytometry.

Management

Immediate

  • Discontinue offending drug (if drug-induced)—most critical step.
  • Hospitalize if ANC <500 or febrile.
  • Empiric broad-spectrum IV antibiotics (piperacillin-tazobactam, meropenem, or cefepime ± vancomycin) within 1 hour of fever.
  • G-CSF (filgrastim 5 µg/kg/day): accelerates neutrophil recovery; standard for drug-induced, chemotherapy, severe congenital. Not routinely for mild chronic neutropenia.
  • Antifungal prophylaxis (posaconazole, micafungin) if prolonged neutropenia expected (>7–10 days).

Supportive

  • Protective isolation (neutropenic precautions) if ANC <500.
  • Transfusions: RBCs for Hb <7–8; platelets for <10k (or <20k if fever).
  • Nutritional support, mouth care, bowel regimen.

Definitive (If Persistent/Recurrent)

  • Hematology referral.
  • Immunosuppression (corticosteroids, IVIG, cyclosporine) for autoimmune causes.
  • Hematopoietic stem cell transplant for severe congenital, aplastic anemia, or MDS.

Prognosis

  • Drug-induced: 80–90% recover in 1–3 weeks after discontinuation + G-CSF.
  • Mortality: 5–10% overall; higher if sepsis, delayed antibiotics, age >65, comorbid malignancy.
  • Clozapine: Rechallenge only under strict protocol if benefits outweigh risks.

Patient Counseling

  • Report fever immediately—do not wait.
  • Avoid crowds, sick contacts, raw foods, gardening during neutropenia.
  • Medication list card for ER visits.
  • Medical alert bracelet if chronic or recurrent.

Agranulocytosis is a hematologic emergency. Rapid recognition, drug cessation, and aggressive infection management save lives.

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