Neutropenia
Related Subjects:
| Neutropenic Sepsis
| Oncological Emergencies
📘 About
- Agranulocytosis refers to a profound fall in circulating neutrophils (a subtype of white cells crucial for innate immunity).
- It dramatically increases susceptibility to bacterial and fungal infection and underpins many cases of neutropenic sepsis.
- Defined as neutrophil count < 0.5 × 10⁹/L or rapidly falling to that level.
🧬 Aetiology & Pathophysiology
- As neutrophil count drops below 1.0 × 10⁹/L, the risk of overwhelming sepsis rises exponentially.
- Mechanisms include bone marrow suppression, immune destruction, or abnormal marrow infiltration.
- Carbimazole and cytotoxic drugs act via marrow suppression, whereas autoimmune and infectious causes act via peripheral destruction or consumption.
🔍 Causes
- Post-chemotherapy: Classically develops 7–14 days after treatment when bone marrow recovery is lowest (nadir phase).
- Physiological: “Benign ethnic neutropenia” in individuals of African or Middle Eastern ancestry, with normal baseline counts 0.8–1.5 × 10⁹/L.
- Infectious: Brucella, Typhoid, Miliary TB, viral infections (EBV, HIV, Hepatitis), protozoa.
- Autoimmune: SLE, Felty’s syndrome (RA + splenomegaly + neutropenia).
- Endocrine / Genetic: Hypopituitarism, hypothyroidism, congenital or familial neutropenia.
💊 Common Drug Causes of Neutropenia
- Cytotoxic drugs: Cyclophosphamide, Methotrexate, 5-Fluorouracil, Busulfan.
- Antithyroid drugs: Carbimazole, Propylthiouracil - rare but potentially fatal idiosyncratic reaction.
- Other drugs: ACE inhibitors, NSAIDs, antimalarials, anticonvulsants (carbamazepine, phenytoin), antidiabetics (metformin, sulphonylureas), β-lactam antibiotics, co-trimoxazole, clozapine, antidepressants.
📊 Classification of Neutropenia
- Mild: 1.0–1.5 × 10⁹/L
- Moderate: 0.5–1.0 × 10⁹/L
- Severe: < 0.5 × 10⁹/L - high risk of sepsis
🩺 Clinical Approach & Management
- Immediate Actions: Stop potential causative drug; assess for infection; initiate neutropenic sepsis protocol if febrile or unwell.
- Investigations: FBC, CRP, U&E, blood & urine cultures, CXR; inspect oral mucosa, skin, and IV lines.
- Supportive Care: Barrier nursing, oral hygiene (chlorhexidine mouthwash), clean diet, and good hand hygiene.
- Consider: G-CSF (Filgrastim) in prolonged or chemotherapy-induced neutropenia; Palifermin to reduce mucositis risk.
💉 Standard Empiric Therapy for Febrile Neutropenia
- Piperacillin/Tazobactam (Tazocin): 4.5 g IV every 6–8 h.
Dose adjust by renal function:
eGFR > 40 → QDS
| 40–20 → TDS
| < 20 → BD.
- Gentamicin: IV once daily - add if severe sepsis or suspected Gram-negative focus.
- If CAP suspected → add oral Doxycycline 200 mg stat, then 100 mg OD,
or if unable to take PO, IV Clarithromycin 500 mg BD.
- If MRSA suspected (line-associated / skin source) → add IV Vancomycin (per dosing calculator; watch nephrotoxicity with aminoglycosides).
- If VRE previously isolated → replace Vancomycin with Linezolid 600 mg BD or Daptomycin 6 mg/kg OD.
- If fever persists > 48–72 h despite therapy → evaluate for fungal or resistant infection and escalate appropriately.
🧫 Alternative Empiric Regimens
- Meropenem: 1 g IV TDS - ideal for MDR organisms or severe penicillin allergy.
- Cefepime: 2 g IV BD - alternative broad-spectrum monotherapy.
- Ceftazidime: 2 g IV TDS - good Pseudomonas cover, especially in high-risk units.
🦠 Antifungal Escalation (Persistent Fever ≥72 h)
- Amphotericin B: broadest coverage for severe systemic fungal infection.
- Fluconazole: first-line for Candida (if no resistance or mould infection suspected).
- Posaconazole / Voriconazole: extended spectrum for Aspergillus or refractory cases.
🧠 Teaching Point
Agranulocytosis exemplifies how drug safety depends as much on education as on monitoring.
Carbimazole-induced agranulocytosis is unpredictable - not dose-dependent - so every patient must receive a written warning card.
Neutropenia from chemotherapy or drugs is a medical emergency once fever develops: antibiotics within 1 hour saves lives.
📚 References
🕓 Revisions
- 2025-10 - Reviewed and edited by Dr O’Kane (Makindo edition)
