What is the best course of action for a patient presenting with leukocytosis, neutrophilia, thrombocytosis, and mild hypochloremia, with a chloride level just below the normal range?

Management of Leukocytosis, Neutrophilia, Thrombocytosis, and Mild Hypochloremia

The most critical first step is to verify these abnormalities are real and not spurious by examining a peripheral blood smear, as platelet clumping can falsely elevate both WBC and platelet counts while simultaneously causing pseudothrombocytopenia. 1

Immediate Verification and Assessment

• Examine a peripheral blood smear immediately to exclude spurious leukocytosis and thrombocytosis caused by platelet clumping, which can be erroneously counted as white blood cells by automated counters 1
• Assess for signs of infection or malignancy, as leukocytosis >17 × 10⁹/L with neutrophilia may indicate infection (commonly chest or urinary), while the combination of leukocytosis, neutrophilia, and thrombocytosis can represent paraneoplastic syndromes from solid tumors or myeloproliferative neoplasms 2, 3
• Evaluate for reactive causes first: trauma, stress, inflammation, or recent surgery commonly cause leukocytosis (45% of cases) and neutrophilia (60% of cases) at presentation 2

Addressing the Hypochloremia

• The mild hypochloremia (just below 98 mEq/L) requires assessment of volume status and concurrent electrolytes to determine if this represents depletion versus dilution 4
• Check serum sodium, potassium, and spot urinary electrolytes to distinguish between true chloride depletion (low urinary chloride) versus renal losses (elevated urinary chloride) 4
• If the patient is on diuretics, consider diuretic-induced hypochloremia, which may require adjustment of diuretic therapy or chloride supplementation 4
• Maintain serum potassium above 4.0 mEq/L and magnesium above 1.8 mg/dL, as electrolyte abnormalities can trigger complications including arrhythmias 2

Ruling Out Myeloproliferative Neoplasms

• Order BCR::ABL1 testing (PCR and/or FISH) and karyotype to exclude chronic myeloid leukemia, which can rarely present without marked leukocytosis (aleukemic phase CML) but still shows neutrophilia, basophilia, and thrombocytosis 5
• Check JAK2 V617F mutation, CALR, and MPL mutations if thrombocytosis persists and myeloproliferative neoplasm is suspected, particularly if platelet count approaches or exceeds 450,000/μL 2, 6
• Perform peripheral blood flow cytometry if chronic lymphocytic leukemia is a consideration, though this typically presents with lymphocytosis rather than neutrophilia 7
• Note that 45% of aleukemic CML cases are initially misdiagnosed before cytogenetic results become available, making molecular testing essential even without marked leukocytosis 5

Management Based on Thrombocytosis Severity

• For platelet counts <1,500,000/μL without symptoms, observation is appropriate as hemorrhagic complications typically occur only at higher thresholds 6
• Aspirin 81-100 mg daily should be considered if cardiovascular risk factors are present or if the patient has essential thrombocythemia, though this requires confirmed diagnosis first 6
• Cytoreductive therapy (hydroxyurea or pegylated interferon-α) is indicated only if platelet count exceeds 1,500,000/μL, symptomatic thrombosis occurs, or confirmed myeloproliferative neoplasm with high-risk features is present, with target platelet count <400,000/μL 6

Infection Surveillance and Prophylaxis

• Monitor for fever, as temperature >38°C (100.4°F) requires immediate evaluation for infection, particularly if neutrophil count is elevated due to underlying infection rather than reactive causes 8
• Obtain cultures (blood, urine, chest imaging) if infection is suspected based on clinical presentation, especially with leukocytosis >17 × 10⁹/L 2
• Antimicrobial prophylaxis is NOT indicated for leukocytosis and neutrophilia; prophylaxis is reserved for neutropenia (ANC <1,000/mm³) 8

Monitoring Strategy

• Repeat complete blood count in 1-2 weeks to determine if abnormalities are persistent or transient reactive changes 2, 7
• If counts normalize, reactive cause is confirmed and no further workup is needed 2
• If leukocytosis, neutrophilia, and thrombocytosis persist beyond 4 weeks, proceed with bone marrow biopsy and comprehensive molecular testing for myeloproliferative neoplasms 2, 5
• Monitor electrolytes weekly until chloride normalizes, particularly if diuretic therapy is adjusted 4

Critical Pitfalls to Avoid

• Do not assume automated counts are accurate without smear verification, as spurious results from platelet clumping are common and lead to unnecessary investigations 1
• Do not overlook aleukemic CML, which presents with neutrophilia and thrombocytosis but without marked leukocytosis in 45% of initially misdiagnosed cases 5
• Do not treat mild hypochloremia aggressively without determining the underlying cause, as inappropriate chloride supplementation can worsen electrolyte imbalances 4
• Do not initiate cytoreductive therapy for thrombocytosis without confirmed diagnosis of myeloproliferative neoplasm, as reactive thrombocytosis requires only observation 6