Evaluation of Elevated WBC, Neutrophils, and Platelets
The combination of elevated WBC count, neutrophilia, and thrombocytosis requires immediate assessment for bacterial infection first, followed by systematic exclusion of myeloproliferative neoplasms if infection is ruled out.
Initial Diagnostic Approach
Immediate Laboratory Assessment
Obtain a manual differential count immediately to assess for left shift (band forms ≥16% or absolute band count ≥1,500 cells/mm³), as automated analyzers are insufficient for accurate band assessment 1, 2, 3.
Calculate the absolute band count by multiplying total WBC by band percentage—an absolute band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for documented bacterial infection 1, 2.
Assess neutrophil percentage—a neutrophil proportion ≥90% yields a likelihood ratio of 7.5 for bacterial infection 1, 2.
Review the peripheral blood smear to evaluate platelet morphology, assess for immature granulocytes, identify dysplasia, and confirm the automated differential 4, 5.
Clinical Assessment for Infection
Evaluate for signs of bacterial infection or sepsis: fever (>38°C) or hypothermia (<36°C), hypotension (systolic BP <90 mmHg), tachycardia (>100 bpm), tachypnea (>20/min), or altered mental status 1, 2.
Perform targeted symptom assessment based on potential infection sources:
- Respiratory: cough, dyspnea, chest pain—obtain pulse oximetry and chest radiography if hypoxemia is present 1
- Urinary: dysuria, flank pain, increased frequency, new incontinence—obtain urinalysis for leukocyte esterase/nitrite and microscopic examination, then urine culture only if pyuria is present 1, 3
- Skin/soft tissue: erythema, warmth, fluctuance—consider aspiration or biopsy if unusual pathogens suspected 1
- Gastrointestinal: diarrhea, abdominal pain—evaluate for C. difficile if colitis symptoms present 1
Obtain blood cultures immediately before antibiotic administration if bacteremia is suspected clinically 2.
Measure inflammatory markers: CRP >50 mg/L has 98.5% sensitivity for probable or definite sepsis 2.
Management of Suspected Bacterial Infection
Initiate broad-spectrum empiric antibiotics within 1 hour if sepsis is suspected, targeting therapy based on suspected source and local resistance patterns 2.
Provide aggressive fluid resuscitation for hypotension, with vasopressor support if hypotension persists despite fluids 2.
Implement source control measures: remove infected catheters, drain abscesses 2.
Evaluation for Myeloproliferative Neoplasms
If infection is excluded or the patient remains asymptomatic with persistent cytopenias/cytoses, evaluate for primary hematologic disorders.
Essential Thrombocythemia (ET) Evaluation
Assess platelet count threshold: sustained platelet count ≥450 × 10⁹/L during the work-up period meets the first WHO criterion for ET 6.
Exclude reactive thrombocytosis causes: iron deficiency, splenectomy, surgery, infection, inflammation, connective tissue disease, metastatic cancer, and lymphoproliferative disorders 6.
Order JAK2V617F mutation testing or other clonal markers; in mutation-negative patients, clinical assessment is required 6.
Obtain bone marrow biopsy to assess for proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes; no significant increase or left-shift of neutrophil granulopoiesis should be present in ET 6.
Exclude other myeloid neoplasms: ensure criteria are not met for polycythemia vera (PV), primary myelofibrosis (PMF), chronic myeloid leukemia (CML via BCR-ABL testing), or myelodysplastic syndrome (MDS) 6.
Primary Myelofibrosis (PMF) Evaluation
Consider prefibrotic PMF if there is mild to moderate leukocytosis, mild to marked thrombocytosis, hypercellularity with neutrophilic proliferation, megakaryocytic proliferation with atypia (clustering, abnormally lobulated nuclei), and minimal or absent reticulin fibrosis 6.
Obtain cytogenetic studies at the time of diagnostic bone marrow examination to identify abnormalities such as del(20q), del(5q), or unbalanced translocations 6.
Polycythemia Vera (PV) Consideration
- Assess hemoglobin and hematocrit levels to exclude PV; failure of iron replacement therapy to increase hemoglobin to the PV range in the presence of decreased serum ferritin helps exclude PV 6.
Special Population Considerations
Elderly Patients
Do not obtain urinalysis or urine culture in truly asymptomatic elderly patients, even with leukocytosis, as asymptomatic bacteriuria prevalence is 15-50% in non-catheterized long-term care residents and does not indicate infection 1, 3.
Recognize atypical presentations: altered mental status or new confusion may be the sole manifestation of systemic bacterial infection in older adults 1.
Left shift has particular diagnostic importance in elderly patients due to decreased basal body temperature and frequent absence of typical infection symptoms 1, 2, 3.
Critical Pitfalls to Avoid
Do not rely on automated differential alone—manual differential is essential for accurate band assessment 1, 2, 3.
Do not ignore left shift when total WBC is normal—this combination still indicates significant bacterial infection requiring evaluation 1, 2, 3.
Do not dismiss the possibility of ET if a reactive cause is present—the presence of a condition associated with reactive thrombocytosis does not exclude ET if the first three WHO criteria are met 6.
Do not treat with antibiotics based solely on laboratory findings if the patient is truly asymptomatic and hemodynamically stable after thorough assessment 3.
Do not overlook medication-induced causes: corticosteroids, lithium, beta-agonists, and epinephrine can cause neutrophilia with left shift 1, 7.
When to Refer to Hematology
Refer immediately if unexplained cytopenias or cytoses persist after excluding infection and reactive causes 6, 4, 5.
Refer urgently if peripheral smear shows dysplasia, immature cells, or monomorphic lymphocyte populations concerning for lymphoproliferative neoplasm 4, 5.
Refer for bone marrow biopsy consideration if primary hematologic disorder is suspected based on clinical and laboratory findings 6, 4, 5.