What is the best course of action for a stable adult patient with a one-year history of elevated white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and hematocrit (Hct)?

Evaluation and Management of Persistent Polycythemia

A stable adult patient with one-year elevation of WBC, RBC, hemoglobin, and hematocrit requires immediate hematology referral to evaluate for polycythemia vera (PV), a myeloproliferative neoplasm that significantly increases thrombotic risk and mortality if untreated.

Initial Diagnostic Workup

The persistent elevation of all cell lines over one year strongly suggests a primary hematologic disorder rather than a reactive process. The following evaluation is essential:

Laboratory Assessment

• Measure serum erythropoietin level - Low or inappropriately normal EPO in the setting of elevated hemoglobin/hematocrit is characteristic of PV 1
• Obtain peripheral blood smear to assess cell morphology and maturity 2
• Check JAK2 mutation status - Present in the vast majority of PV cases and is a key diagnostic marker 1
• Bone marrow biopsy with histology - Now considered more diagnostically accurate than red cell mass measurement for PV 1
• Assess iron stores (serum ferritin, transferrin saturation) - Iron deficiency can mask the true severity of polycythemia 3

Rule Out Secondary Causes

• Evaluate for chronic hypoxemia - Check oxygen saturation, consider sleep study if indicated, assess for cyanotic heart disease 3
• Review medication history - Certain drugs can cause leukocytosis 2
• Assess for chronic inflammatory conditions - Can cause reactive leukocytosis and thrombocytosis 2
• Screen for smoking, obesity - Both associated with secondary erythrocytosis 2

Risk Stratification for Thrombosis

If polycythemia vera is confirmed, thrombotic risk assessment is critical as thrombosis is the leading cause of morbidity and mortality in PV patients.

Hematocrit Management

• Target hematocrit <45% - Patients with Hct ≥45% have significantly higher thrombotic event rates (HR 1.61) compared to those maintained <45% 4
• This threshold is supported by both prospective trials and real-world Veterans Health Administration data 4

White Blood Cell Count Monitoring

• WBC count independently predicts thrombotic risk in PV patients 4
• Patients with WBC ≥8.5 × 10⁹/L have higher thrombotic rates (HR 1.47) compared to WBC <7 × 10⁹/L 4
• Risk escalates further with WBC ≥11 × 10⁹/L (HR 1.87) 4

Treatment Algorithm

For Confirmed Polycythemia Vera

Cytoreductive therapy is indicated to maintain Hct <45% and reduce thrombotic risk:

1. Therapeutic phlebotomy - First-line for Hct control, removing 1 unit of blood with equal volume replacement 3

   • Avoid aggressive/repeated phlebotomy as this depletes iron stores and paradoxically increases stroke risk 3
   • Monitor iron status during phlebotomy therapy 3

2. Consider myelosuppressive therapy if:

   • Phlebotomy requirements are excessive
   • WBC count remains elevated despite Hct control
   • Patient has high thrombotic risk factors 4

Critical Pitfalls to Avoid

• Do NOT perform routine repeated phlebotomies without monitoring iron status - Iron deficiency reduces oxygen-carrying capacity and increases stroke risk despite lowering hematocrit 3
• Do NOT ignore elevated WBC counts - These independently increase thrombotic risk even when Hct is controlled 4
• Do NOT delay hematology referral - PV requires specialized management to prevent life-threatening thrombotic complications 4

Monitoring Strategy

Ongoing Assessment

• Serial CBC monitoring to assess response to therapy and maintain Hct <45% 4
• Regular WBC count evaluation as part of thrombotic risk assessment 4
• Periodic iron studies to prevent iron deficiency during phlebotomy therapy 3
• Clinical surveillance for thrombotic events - Including stroke, myocardial infarction, deep vein thrombosis 4

Multiorgan Complications

• Renal function monitoring - PV can cause glomerular abnormalities and hyperuricemia 3
• Cardiovascular assessment - Increased risk of ischemic events 4
• Screen for hepatosplenomegaly - Common in myeloproliferative disorders 3

The one-year duration of elevation makes reactive causes less likely and mandates exclusion of PV, which carries significant mortality risk from thrombosis if left untreated. 4