Neutropenia
Neutropenia is a reduced absolute neutrophil count that raises infection risk sharply once the count falls below 500/microL, most often from chemotherapy or another marrow-suppressing or idiosyncratic drug. Diagnosis rests on a repeat CBC with differential and smear review followed by a directed search for cause, and management centers on stopping the offending agent, treating any underlying disease, and using G-CSF and neutropenic precautions when the count is low or the patient is febrile.
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What this article covers
- Overview
Definition: neutropenia is a reduced absolute neutrophil count (ANC), the product of the white blood cell count and the percentage of neutrophils and bands, below 1500 cells/microL (1.5 x 10^9/L).
- Epidemiology
Chemotherapy-induced neutropenia is the dominant cause in hospital and oncology practice, typically developing 5 to 15 days after cytotoxic chemotherapy as the marrow nadir is reached.
- Risk factors
Recent cytotoxic chemotherapy, especially myelosuppressive regimens and induction chemotherapy for acute leukemia, is the leading risk factor.
- Pathophysiology
Three mechanisms lower the ANC: decreased marrow production, increased peripheral destruction (often antibody-mediated), and redistribution out of the circulating pool, most often into the spleen.
- Clinical features
Neutropenia itself is often asymptomatic, discovered incidentally on a routine CBC, particularly in benign ethnic neutropenia and mild drug effects.
- Differential diagnosis
Sepsis with reactive or consumptive neutropenia: overwhelming infection can itself drive the ANC down through consumption and marginalization, distinguished by severe sepsis or septic shock preceding or accompanying the low count (Sepsis).
- Diagnosis
Establish the diagnosis and grade severity by the absolute neutrophil count: neutropenia is an ANC below 1500 cells/microL (1.5 x 10^9/L), graded mild (roughly 1000-1500/microL), moderate (roughly…
- Management
First, identify and stop any offending drug: review the medication list against known culprits (chemotherapy, clozapine, methimazole/propylthiouracil, sulfonamides, dapsone, carbamazepine…
- Complications
Febrile neutropenia and sepsis: the most immediate and life-threatening complication, especially with ANC below 500/microL and anticipated duration beyond 7 days.
- Prognosis
Outcome depends chiefly on how quickly infection is recognized and treated: delayed empiric antibiotics in febrile neutropenia sharply increase mortality, while prompt treatment allows most episodes to resolve without sequelae.
- Prevention
Primary G-CSF prophylaxis with filgrastim 5 mcg/kg subcutaneously daily (or pegfilgrastim 6 mg subcutaneously as a single dose per cycle) starting at least 24 hours after chemotherapy, for any…
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Related articles
- Neutropenic fever
Neutropenic fever is an oncologic emergency defined as a single oral temperature of 38.3 C or higher, or 38.0 C sustained for 1 hour, with an ANC of 500/microL or lower, most often during the chemotherapy nadir. Management is empiric antipseudomonal beta-lactam therapy within 60 minutes, with vancomycin, antifungal therapy, and growth factors added only for specific indications.
- Aplastic anemia
Aplastic anemia is an acquired or inherited hematopoietic stem cell disorder that produces pancytopenia with a hypocellular, fatty bone marrow and no dysplasia, blasts, or fibrosis. Diagnosis rests on marrow biopsy showing less than 25% cellularity with severity graded by the Camitta criteria, and treatment is allogeneic stem cell transplantation for young fit patients with a matched donor or antithymocyte globulin plus cyclosporine and eltrombopag for everyone else.
- Myelodysplastic syndromes
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- Acute myeloid leukemia
Acute myeloid leukemia is a clonal proliferation of myeloid precursors that fails to differentiate, defined by myeloblasts at or above 20% of the bone marrow or blood, and it presents with cytopenias from marrow replacement plus, in acute promyelocytic leukemia, a coagulopathic emergency. Diagnosis rests on marrow blast count, immunophenotype, and cytogenetic and molecular testing that set both classification and risk, while treatment is intensive induction chemotherapy or ATRA-arsenic trioxide for APL, followed by risk-adapted consolidation.
- Pernicious anemia
Pernicious anemia is autoimmune atrophic gastritis that destroys gastric parietal cells and abolishes intrinsic factor production, causing vitamin B12 malabsorption, megaloblastic macrocytic anemia, and a potentially irreversible myelopathy and neuropathy. Diagnosis rests on a low or borderline B12 with an elevated methylmalonic acid, confirmed by anti-intrinsic factor antibody, and treatment is lifelong vitamin B12 replacement.
- Sepsis
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, identified by an acute rise in SOFA score of 2 points or more in a patient with known or suspected infection. Survival depends on recognizing the pattern early and completing the hour-1 bundle: lactate, blood cultures before antibiotics, broad-spectrum antibiotics such as cefepime 2 g IV every 8 hours, and 30 mL/kg crystalloid for hypotension or a lactate of 4 mmol/L or higher.