In a female patient with leukocytosis (white‑blood‑cell count 14.6 ×10^3/µL), neutrophilia (absolute neutrophil count 10,147/µL) and thrombocytosis (platelet count 447 ×10^3/µL), what is the most likely cause and how should it be managed?

Evaluation and Management of Leukocytosis with Neutrophilia and Thrombocytosis in a Female Patient

Most Likely Diagnosis

The most likely cause is a reactive process secondary to bacterial infection, given the combined presence of leukocytosis (WBC 14.6 × 10³/µL), marked neutrophilia (ANC 10,147/µL), and thrombocytosis (platelets 447 × 10³/µL). 1

Immediate Clinical Assessment

Fever and Infection Screening

• Check temperature immediately—a single reading ≥38.3°C or sustained ≥38.0°C for ≥1 hour markedly increases the probability of bacterial infection and mandates empiric antibiotics. 1
• Assess for systemic infection indicators: altered mental status, hypotension, tachycardia, or other signs of sepsis require urgent intervention. 1
• Evaluate for specific infection sources: respiratory symptoms (pneumonia), urinary symptoms (UTI), abdominal pain or peritoneal signs (intra-abdominal infection), skin/soft tissue infections. 1

Key Diagnostic Markers for Bacterial Infection

The neutrophil elevation of 10,147/µL (69.5% of total WBC) carries significant diagnostic weight:

• An absolute band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for documented bacterial infection. 1
• A neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection. 1
• Total WBC ≥14,000 cells/mm³ (this patient has 14,600) has a likelihood ratio of 3.7 for bacterial infection. 1

Thrombocytosis as an Infection Marker

• Infection accounts for nearly half of all secondary thrombocytosis cases in hospitalized patients. 2
• Clinical features associated with infectious thrombocytosis include fever, tachycardia, neutrophilia, leukocytosis, and hypoalbuminemia. 2
• Thrombocytosis secondary to infection typically normalizes more rapidly than non-infectious causes. 2

Immediate Diagnostic Workup

Essential Laboratory Tests

• Obtain two sets of blood cultures from separate sites before initiating antibiotics if fever is present. 1
• Perform urinalysis with culture if urinary symptoms are present. 1
• Order chest radiograph if respiratory symptoms, hypoxemia, or tachypnea are present. 1
• Site-specific cultures as indicated by clinical findings. 1

Additional Testing to Consider

• In patients with cirrhosis and ascites, perform diagnostic paracentesis immediately—any neutrophilia warrants evaluation for spontaneous bacterial peritonitis. 1
• Recent tick exposure requires consideration of tick-borne rickettsial diseases, particularly with headache, fever, or confusion. 1
• Measure inflammatory markers (ESR, CRP) to assess degree of systemic inflammation. 3

Management Algorithm

If Fever Present (≥38.3°C single or ≥38.0°C sustained ≥1 hour)

1. Initiate empiric broad-spectrum antibiotics within 2 hours without delay. 1
2. Obtain all cultures before antibiotics but do not delay treatment. 1
3. Reassess at 48-72 hours: if pathogen identified, de-escalate to targeted therapy; if afebrile and improving, continue current regimen. 1

If Afebrile but Symptomatic

1. Evaluate systematically for occult infection sources: gastrointestinal tract, urinary tract, respiratory tract, skin/soft tissue. 1
2. Consider imaging studies directed at suspected infection source. 1
3. Monitor temperature every 4-6 hours and educate patient to seek immediate care if fever develops. 1

If Completely Asymptomatic

1. Repeat CBC with manual differential in 2-4 weeks to determine if this is transient or persistent. 4
2. Comprehensive medication review to identify drugs that may cause neutrophilia (lithium, beta-agonists, epinephrine). 1
3. Assess for physiologic stressors: recent surgery, trauma, intense exercise can produce neutrophilia with normal or mildly elevated WBC. 1

Differential Diagnosis Beyond Infection

Inflammatory Conditions

• Adult-onset Still's disease (AOSD) presents with leukocytosis (often >15 × 10⁹/L), neutrophilia, thrombocytosis, fever, rash, and arthralgia. 3
• 50% of AOSD patients have WBC counts >15 × 10⁹ cells/L, and 37% have counts >20 × 10⁹ cells/L. 3
• Reactive thrombocytosis is common in AOSD due to chronic inflammation. 3

Myeloproliferative Neoplasms (Less Likely at These Levels)

• Essential thrombocythemia is the most common cause of primary thrombocytosis and typically presents with extreme (>800 × 10⁹/L) and prolonged (>1 month) platelet elevation. 2
• Polycythemia vera can present with neutrophilia and thrombocytosis, but typically has elevated hemoglobin/hematocrit. 5
• Chronic myeloid leukemia classically presents with marked leukocytosis (often >25 × 10⁹/L), left-shifted neutrophilia, basophilia, and thrombocytosis—but this patient's counts are too modest. 6

Critical Pitfalls to Avoid

• Do not ignore neutrophilia of 10,147/µL even though total WBC is only mildly elevated (14.6 × 10³/µL)—the absolute neutrophil count is the critical parameter. 1
• Do not delay empiric antibiotics while awaiting culture results if fever is present—the 2-hour window is mandatory. 1
• Do not assume thrombocytosis is benign—it may be the first clue to an underlying infection, particularly in patients with comorbidities. 2
• Do not treat asymptomatic patients with antibiotics based solely on elevated neutrophil counts without evidence of infection. 1
• Do not overlook spontaneous bacterial peritonitis in cirrhotic patients—any neutrophilia mandates diagnostic paracentesis. 1

Monitoring and Follow-Up

• If infection is confirmed, continue antibiotics for appropriate duration based on pathogen and source. 1
• Repeat CBC after infection resolution to ensure normalization of WBC, neutrophils, and platelets. 2
• If counts remain elevated after 4-6 weeks without identified infection, consider bone marrow evaluation to exclude myeloproliferative neoplasm. 7
• Weekly CBC monitoring is appropriate if neutrophilia persists without clear etiology. 4