Management of Leukocytosis (WBC 14.3 × 10⁹/L)
For a patient with moderate leukocytosis (WBC 14.3) and elevated hemoglobin/hematocrit, the immediate priority is determining whether this represents reactive leukocytosis from infection/inflammation versus a primary hematologic disorder, while simultaneously assessing for any signs of leukostasis or systemic infection that require urgent intervention. 1
Immediate Assessment
Obtain a peripheral blood smear with differential immediately to evaluate white blood cell types, maturity, and morphology, as this distinguishes benign reactive causes from malignancy far more effectively than the total count alone. 1, 2 The differential will reveal whether this is neutrophilic (suggesting infection/stress), lymphocytic (viral illness), or shows immature forms (concerning for leukemia). 2, 3
Key Clinical Features to Evaluate
- Assess for infection systematically: fever, localizing symptoms (pneumonia, urinary tract infection, soft tissue infection), and notably diarrhea, as Clostridium difficile infection causes leukocytosis in 16-25% of cases with WBC >15,000. 4
- Screen for physiologic stress: recent surgery, trauma, emotional stress, or exercise can double the WBC count within hours due to demargination from bone marrow storage pools. 2, 3
- Review medications: corticosteroids, lithium, and beta-agonists commonly cause leukocytosis. 3
- Evaluate for symptoms suggesting malignancy: fever with weight loss, bruising, fatigue, or lymphadenopathy warrant immediate hematology referral. 2, 5
Risk Stratification
At WBC 14.3 × 10⁹/L, leukostasis is not a concern as this medical emergency typically occurs only at WBC >100,000/μL. 1, 3 However, the elevated hemoglobin (16.6) and hematocrit (50.9) suggest possible polycythemia vera or secondary erythrocytosis, which changes the differential diagnosis significantly.
When to Suspect Hematologic Malignancy
Refer urgently to hematology/oncology if: 1, 2
- Peripheral smear shows immature cells (blasts, promyelocytes, myelocytes)
- Concurrent unexplained anemia or thrombocytopenia (though this patient has elevated RBC parameters)
- Constitutional symptoms (fever, night sweats, weight loss)
- Splenomegaly or hepatomegaly on examination
Management Based on Most Likely Etiology
If Infection is Suspected
Obtain blood cultures before starting antibiotics if fever is present, then initiate empirical broad-spectrum antimicrobials for febrile patients. 1 For confirmed bacterial infections, the leukocytosis typically resolves with appropriate antimicrobial therapy. 2, 4
Consider C. difficile testing even without diarrhea, as this infection is present in 25% of patients with WBC >30,000 who lack hematologic malignancy, and can occur with minimal gastrointestinal symptoms. 4
If Reactive/Physiologic Cause is Identified
Repeat CBC in 1-2 weeks after addressing the underlying cause (treating infection, discontinuing offending medications, allowing recovery from stress). 2 Most reactive leukocytosis resolves once the stimulus is removed. 3
If Polycythemia Vera is Suspected
The combination of leukocytosis (14.3), elevated RBC count (5.93), hemoglobin (16.6), and hematocrit (50.9) raises concern for a myeloproliferative disorder, particularly polycythemia vera. 5 This requires:
- JAK2 mutation testing
- Erythropoietin level
- Bone marrow biopsy if JAK2 positive
- Hematology referral for definitive diagnosis and management
Critical Pitfalls to Avoid
Never assume malignancy without reviewing the peripheral smear, as reactive leukocytosis from infection or inflammation is exponentially more common than leukemia. 1, 2 In one study, 53% of patients with WBC ≥15,000 had infection as the cause. 4
Do not delay treatment of confirmed infection while investigating the leukocytosis, as the elevated WBC is often the appropriate physiologic response. 1, 3
Avoid extensive antibiotic courses for "unexplained" leukocytosis in hospitalized patients, as this often represents persistent inflammation-immunosuppression and catabolism syndrome (PICS) rather than active infection, and prolonged antibiotics lead to C. difficile colonization and resistance without benefit. 6