Hematology · Neutropenia and Febrile Neutropenia
The facts most likely to be tested
Febrile neutropenia is defined as a single oral temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) sustained for over one hour in a patient with an absolute neutrophil count (ANC) <500 cells/mm³.
Pseudomonas aeruginosa is the most common and dangerous Gram-negative pathogen in febrile neutropenia, necessitating immediate empiric coverage with anti-pseudomonal beta-lactams like cefepime, piperacillin-tazobactam, or meropenem.
Patients with febrile neutropenia often lack the classic signs of inflammation, such as purulence or erythema, because they cannot mount an adequate neutrophilic response to infection.
The MASCC (Multinational Association for Supportive Care in Cancer) risk index is used to stratify patients into low-risk or high-risk categories to determine if outpatient oral antibiotic therapy is appropriate.
Granulocyte colony-stimulating factor (G-CSF), such as filgrastim, is indicated for secondary prophylaxis in patients who have experienced a prior episode of febrile neutropenia or for those at high risk of complications.
Cyclic neutropenia is a rare autosomal dominant disorder characterized by regular, periodic oscillations in neutrophil counts, typically occurring every 21 days.
Severe chronic neutropenia (e.g., Kostmann syndrome) significantly increases the risk of periodontitis, gingivitis, and recurrent skin abscesses due to impaired host defense.
Vignette unlocked
A 54-year-old woman with metastatic breast cancer currently undergoing chemotherapy presents to the emergency department with a fever of 38.5°C (101.3°F). She reports no cough, dysuria, or abdominal pain. Physical examination reveals a port-a-cath site that is clean without erythema or tenderness. Her absolute neutrophil count (ANC) is 200 cells/mm³.
What is the most appropriate next step in management?
Initiation of empiric intravenous anti-pseudomonal beta-lactam monotherapy
The patient meets the criteria for febrile neutropenia (ANC <500 and fever), requiring immediate empiric coverage for high-risk pathogens like Pseudomonas, even in the absence of a clear infectious source.
Full handout
High yield triage
Etiology / Epidemiology
Defined as ANC < 1500/µL. Common causes include chemotherapy, leukemia, and drug-induced suppression.
Clinical Manifestations
Often asymptomatic until infection occurs. Fever is the hallmark sign; look for stomatitis or cellulitis.
Diagnosis
Diagnosis via Complete Blood Count (CBC) with differential. ANC < 500/µL defines severe neutropenia.
Treatment
Treat febrile neutropenia with Cefepime or Piperacillin-tazobactam. Avoid rectal exams to prevent translocation.
Prognosis
Risk of sepsis is high. Mortality correlates with duration of ANC < 100/µL.
Full handout
Epidemiology & Etiology
Neutropenia is most frequently iatrogenic, secondary to cytotoxic chemotherapy. Other etiologies include aplastic anemia, myelodysplastic syndromes, and severe B12/folate deficiency. Viral infections like EBV or HIV are common transient causes.
Pertinent Anatomy
Neutrophils are produced in the bone marrow and released into the peripheral blood. They migrate to tissues via diapedesis to combat bacterial and fungal pathogens.
Pathophysiology
Reduced production or increased peripheral destruction leads to a failure of the innate immune response. Without neutrophils, the body cannot form pus, leading to atypical infection presentations. The risk of opportunistic infection increases exponentially as the ANC drops below 500/µL.
Clinical Manifestations
Patients often present with fever > 38.3°C as the only sign of occult infection. Physical exam may reveal oral ulcers, gingivitis, or perirectal abscesses. Septic shock can develop rapidly; monitor for hypotension and altered mental status.
Diagnosis
The Absolute Neutrophil Count (ANC) is calculated as (Total WBC) × (% Neutrophils + % Bands). ANC < 1500/µL is mild, < 1000/µL is moderate, and < 500/µL is severe. A bone marrow biopsy is indicated if the cause remains unexplained after initial workup.
Treatment
Febrile neutropenia is a medical emergency requiring empiric broad-spectrum antibiotics within 60 minutes. Cefepime or Piperacillin-tazobactam are the first-line choices. Do not use NSAIDs as they mask fever. Use Filgrastim (G-CSF) to stimulate marrow recovery in high-risk patients.
Prognosis
The primary complication is sepsis and multi-organ failure. Patients with ANC < 100/µL require strict neutropenic precautions and prophylactic antifungals/antibiotics.
Differential Diagnosis
Leukemia: presence of blasts on peripheral smear
Aplastic Anemia: pancytopenia with hypocellular marrow
B12 Deficiency: macrocytic anemia with hypersegmented neutrophils
Drug-induced: history of recent medication initiation
Viral infection: transient drop with lymphocytosis