Neutropenia

Drug-Induced Neutropenia

• Etiology & Culprit Drugs:

  • Direct toxic suppression vs. immune-mediated destruction of myeloid precursors.
  • Antithyroid: Methimazole, PTU (classic vignette: Graves pt with sudden fever/sore throat).
  • Psychotropics: Clozapine (requires routine ANC monitoring), Carbamazepine, Valproate.
  • Antibiotics/Others: TMP-SMX, Dapsone, high-dose β-lactams, Methotrexate, Sulfasalazine.

• Clinical Presentation:

  • Sudden high fever, chills, malaise.
  • Oropharyngeal lesions: Severe pharyngitis, painful oral ulcers/stomatitis, dysphagia. c
  • Absence of purulence/pus at infection sites due to lack of WBCs.

• Diagnosis:

  • CBC with diff: Severe neutropenia / Agranulocytosis defined as ANC < 500/µL. c
    • But RBC and platelets counts are normal
  • Blood cultures: ≥ 2 sets (peripheral + central line) before starting Abx.
  • Peripheral blood smear: Decreased mature granulocytes; rules out blasts/dysplasia.
  • Bone marrow biopsy (only if persistent/unclear): Myeloid maturation arrest or myeloid hypoplasia.

• High-Yield Differentials:

  • Aplastic Anemia: Presents with pancytopenia + hypocellular fatty marrow (vs. isolated neutropenia).
  • Acute Leukemia (AML/ALL): Shows ≥ 20% blasts on smear/marrow + organomegaly.
  • Felty Syndrome: Triad of Rheumatoid Arthritis + splenomegaly + neutropenia.

• Management:

  1. Immediate Step: Discontinue offending drug immediately.
  2. Febrile Neutropenia (Temp ≥ 38.3°C [101°F] + ANC < 500/µL):
     • Emergency empiric IV anti-pseudomonal monotherapy: Cefepime, Piperacillin-Tazobactam (Zosyn), or Meropenem.
     • Add Vancomycin only if: Hemodynamic instability, suspected central-line infection, severe mucositis, or MRSA colonization.
  3. Adjunct: G-CSF (Filgrastim) to accelerate neutrophil recovery.
  4. Refractory Fever (> 4–7 days on broad-spectrum Abx): Add empiric antifungal (Voriconazole, Caspofungin, or Liposomal Amphotericin B).
  5. Contraindications: Strictly avoid digital rectal exams (DRE), rectal temps, or enemas (risk of mucosal tear → bacteremia).

• Complications:

  • Pseudomonal / GNR sepsis and septic shock.
  • Typhlitis (neutropenic enterocolitis).
  • Opportunistic fungal infections (Candida, Aspergillus).