Management of Leukocytosis, Thrombocytosis, Neutrophilia, and Proteinuria
The immediate priority is to rule out infection as the cause of this patient's leukocytosis with neutrophilia and proteinuria, while simultaneously evaluating for a primary myeloproliferative neoplasm or chronic myeloid leukemia (CML). 1, 2, 3
Initial Diagnostic Workup
Immediate Laboratory Testing
- Peripheral blood smear review is mandatory to assess white blood cell morphology, maturity, and to exclude spurious counts from platelet clumping 4, 5
- BCR-ABL1 testing via FISH or RT-PCR must be performed immediately to confirm or exclude CML, as this fundamentally changes management 1, 2
- Metabolic panel with uric acid, LDH, and phosphate to assess for tumor lysis syndrome risk 2
- Urinalysis with microscopy and urine culture given the proteinuria and epithelial cells 6
Clinical Assessment for Infection
The combination of neutrophilia (8.22 × 10⁹/L), leukocytosis (WBC 12 × 10⁹/L), and proteinuria strongly suggests an infectious etiology, particularly given that infection accounts for nearly half of all secondary thrombocytosis cases 3. Key clinical features to evaluate include:
- Fever, tachycardia, or weight loss - these are strongly associated with infectious causes of thrombocytosis 3
- Fresh-water exposure history - the combination of proteinuria, fever, and leukocytosis could indicate leptospirosis 6
- Indwelling prostheses, dementia, diabetes, or paralysis - demographic factors associated with infectious thrombocytosis 3
Management Algorithm
If Infection is Suspected or Confirmed
Empirical broad-spectrum antimicrobial therapy must be initiated immediately if the patient is febrile, even before culture results return 7. First-line options include:
- Levofloxacin 500mg orally daily, or
- Ciprofloxacin 500mg orally twice daily 7
- For severe cases: ceftazidime, meropenem, or other IV broad-spectrum antibiotics 7
For suspected leptospirosis (given proteinuria and potential water exposure): penicillin or tetracycline antibiotics during the bacteremic phase, though severe disease may progress despite therapy 6
If CML is Confirmed (BCR-ABL1 Positive)
Tyrosine kinase inhibitor therapy should be started immediately 1, 2:
- Imatinib is the first-line treatment for chronic phase CML 1, 2
- Hydroxyurea 50-60 mg/kg/day can be used for rapid cytoreduction if symptomatic leukocytosis is present 1, 2
- BCR-ABL transcript levels every 3 months during treatment 1, 2
- Bone marrow cytogenetics at 6 and 12 months from therapy initiation 1, 2
If Primary Myeloproliferative Neoplasm is Suspected
Hydroxyurea is the first-line cytoreductive agent for both symptomatic thrombocytosis and leukocytosis 1:
- For thrombocytosis: 2-4 g per day to restore platelets <400 × 10⁹/L 1
- For leukocytosis: 50-60 mg/kg per day until WBC <10-20 × 10⁹/L 1
Monitoring Strategy
- Complete blood counts weekly until stable, then every 2-4 weeks 1
- Daily fever trends and renal function if infection suspected, until afebrile 7
- Repeat urinalysis after treatment to document clearance of proteinuria 6
Critical Pitfalls to Avoid
Do not assume thrombocytosis is benign - it may be the first clue to underlying infection or malignancy 3. The combination of leukocytosis, neutrophilia, and thrombocytosis has a higher mortality risk when secondary to infection compared to non-infectious causes 3.
Verify automated counts with peripheral smear - spurious leukocytosis can occur from platelet clumping being counted as WBCs, leading to unnecessary investigations 5.
Do not delay BCR-ABL testing - CML requires immediate tyrosine kinase inhibitor therapy, and delays worsen outcomes 1, 2.