Hematology · White Blood Cell Disorders
The facts most likely to be tested
Febrile neutropenia is defined as an absolute neutrophil count (ANC) < 500/µL with a single oral temperature of ≥ 38.3°C (101°F) or a sustained temperature of ≥ 38.0°C (100.4°F) for over one hour.
Clozapine is the classic medication associated with agranulocytosis, necessitating mandatory serial CBC monitoring to prevent life-threatening infection.
Cyclic neutropenia presents with recurrent fevers, stomatitis, and periodontitis occurring in predictable 21-day cycles due to mutations in the ELANE gene.
Felty syndrome is the clinical triad of rheumatoid arthritis, splenomegaly, and neutropenia.
Bone marrow biopsy is the diagnostic gold standard for persistent, unexplained leukopenia to rule out myelodysplastic syndrome or leukemia.
Pseudoneutropenia occurs due to margination of neutrophils along the vascular endothelium, often seen in patients with splenomegaly or chronic infection.
Empiric broad-spectrum antibiotics covering Pseudomonas aeruginosa (e.g., cefepime, piperacillin-tazobactam) must be initiated immediately in any patient with febrile neutropenia.
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A 58-year-old female with a history of rheumatoid arthritis presents for evaluation of recurrent mouth ulcers and fatigue. Physical examination reveals splenomegaly and tender, swollen joints in the hands. Laboratory studies demonstrate a white blood cell count of 2,200/µL with an absolute neutrophil count of 800/µL. Her hemoglobin is 10.2 g/dL and platelets are 140,000/µL.
What is the most likely diagnosis?
Felty syndrome
The patient presents with the classic triad of rheumatoid arthritis, splenomegaly, and neutropenia, which defines Felty syndrome as outlined in the fourth bet.
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Etiology / Epidemiology
Defined as WBC < 4,000/µL. Common causes include viral infections, autoimmune disorders, and chemotherapy.
Clinical Manifestations
Often asymptomatic; presents with recurrent infections, stomatitis, or fever.
Diagnosis
Complete Blood Count (CBC) with differential is the gold standard. Bone marrow biopsy is indicated for unexplained cases.
Treatment
Treat underlying cause. Granulocyte colony-stimulating factor (G-CSF) for severe cases. Avoid NSAIDs in neutropenic fever.
Prognosis
Risk of sepsis is the primary concern. Mortality correlates with the absolute neutrophil count (ANC).
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Epidemiology & Etiology
Leukopenia is frequently secondary to viral suppression (e.g., HIV, EBV) or bone marrow infiltration. Autoimmune conditions like Systemic Lupus Erythematosus are classic systemic causes. Drug-induced etiologies are common, particularly with chemotherapy and antithyroid medications.
Pertinent Anatomy
The bone marrow is the primary site of leukocyte production. The spleen acts as a reservoir; splenomegaly can cause sequestration, leading to peripheral leukopenia despite normal marrow production.
Pathophysiology
Leukopenia results from decreased production, increased destruction, or peripheral sequestration. Stem cell failure leads to pancytopenia, while selective destruction of neutrophils causes agranulocytosis. The clinical risk is inversely proportional to the ANC < 500/µL, which defines severe risk for opportunistic infection.
Clinical Manifestations
Patients often present with fever of unknown origin or mucosal ulcerations. Neutropenic fever (temp > 38.3°C with ANC < 500) is a medical emergency requiring immediate intervention. Look for gingival necrosis or recurrent skin abscesses as signs of impaired host defense.
Diagnosis
The CBC with differential is the initial diagnostic step. A Bone marrow biopsy is required if the etiology remains unclear or if malignancy is suspected. ANC < 1,500/µL is the clinical threshold for leukopenia, while ANC < 500/µL indicates high infection risk.
Treatment
Management focuses on identifying the offending agent or underlying disease. G-CSF (filgrastim) is the standard for drug-induced or chemotherapy-related neutropenia. Empiric broad-spectrum antibiotics (e.g., cefepime) must be started immediately in patients with fever. Discontinue all suspected myelosuppressive drugs.
Prognosis
The primary complication is sepsis and secondary fungal infections. Patients require serial CBC monitoring until counts normalize. Mortality is significantly higher if the nadir of the neutrophil count is prolonged.
Differential Diagnosis
Aplastic Anemia: pancytopenia with hypocellular marrow
HIV/AIDS: CD4 depletion and viral suppression
SLE: immune-mediated peripheral destruction
Hypersplenism: sequestration of leukocytes
B12/Folate Deficiency: ineffective hematopoiesis