Evaluation of a Female Patient with Fever, Headache, Leukocytosis, and Polycythemia
The patient with fever, headache, leukocytosis (WBC 15,000/mm³), and polycythemia (Hb 19 g/dL, HCT 61%) requires urgent evaluation for polycythemia vera with potential hyperviscosity syndrome, along with workup for infectious causes.
Initial Diagnostic Approach
Immediate Laboratory Testing
- Complete blood count with manual differential to confirm leukocytosis and assess for left shift 1
- Blood cultures (at least 2 sets) before initiating antibiotics 1
- Comprehensive metabolic panel to assess organ function
- Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) 1
- Urinalysis and urine culture 1
- Coagulation studies (PT, PTT, INR)
- JAK2 V617F mutation testing (for polycythemia vera)
- Erythropoietin level (will be low in polycythemia vera)
Imaging Studies
- Chest radiograph to evaluate for pneumonia or other pulmonary pathology 1
- Consider contrast-enhanced CT scan of chest/abdomen/pelvis if source of infection unclear 2
- Consider head CT or MRI if neurological symptoms present beyond headache 2
Differential Diagnosis Based on Clinical Presentation
Primary Hematologic Concerns
- Polycythemia vera (most likely given Hb 19, HCT 61)
- Stress erythrocytosis (dehydration, high altitude)
- Secondary polycythemia (hypoxic conditions, smoking)
Infectious Considerations
- Bacterial infections (likelihood ratio for bacterial infection with WBC >14,000/mm³ is 3.7) 1
Other Considerations
- Malignancy with paraneoplastic syndrome
- Autoimmune disorders
- Drug reactions
Management Algorithm
For Polycythemia
If signs of hyperviscosity present (headache, visual disturbances, confusion):
- Immediate therapeutic phlebotomy to reduce hematocrit below 45%
- Hydration with IV fluids
For confirmed polycythemia vera:
- Hematology consultation
- Low-dose aspirin (81-100 mg daily) if no contraindications
- Consider cytoreductive therapy based on risk stratification
For Infectious Etiology
If sepsis suspected (based on vital signs, clinical appearance):
- Start empiric broad-spectrum antibiotics after cultures 1
- Consider vancomycin plus piperacillin-tazobactam or cefepime
If CNS infection suspected (meningeal signs, altered mental status):
If respiratory infection suspected:
- Respiratory fluoroquinolone or β-lactam plus macrolide 1
Special Considerations
Polycythemia with Fever
- Polycythemia vera can present with constitutional symptoms including fever
- However, concurrent infection must be ruled out as patients with polycythemia are at increased risk for thrombotic events and complications
Headache Evaluation
- Headache in the setting of polycythemia may indicate hyperviscosity syndrome requiring urgent intervention
- Consider cerebral venous sinus thrombosis, particularly with severe or persistent headache 4
- Evaluate for meningitis/encephalitis if fever and headache are accompanied by neck stiffness or altered mental status 2
Common Pitfalls to Avoid
- Attributing all symptoms to a single diagnosis: Both polycythemia and infection may be present simultaneously
- Delaying phlebotomy: In symptomatic polycythemia, therapeutic phlebotomy should not be delayed
- Overlooking occult infection: Fever and leukocytosis warrant thorough infectious workup even when another diagnosis seems likely 1
- Failing to consider travel history: Important for tropical diseases like malaria which can present with fever, headache, and hematologic abnormalities 2
- Relying on a single CBC measurement: Serial monitoring is essential to track response to interventions 1
Follow-up Recommendations
- Daily CBC to monitor response to phlebotomy and/or antibiotics
- Hematology consultation within 24-48 hours for management of polycythemia
- Infectious disease consultation if source of infection unclear or patient not responding to empiric therapy