Polycythemia Vera
Polycythemia vera is the disease most likely to present with simultaneous elevation of both red blood cells (erythrocytosis) and white blood cells (leukocytosis), as this myeloproliferative neoplasm causes clonal proliferation of all three myeloid cell lines.
Key Distinguishing Features
Why Not Infection?
While bacterial infections commonly cause leukocytosis with left shift, they do not cause true erythrocytosis (elevated red blood cell mass). The evidence clearly demonstrates:
Bacterial infections cause leukocytosis: WBC ≥14,000 cells/mm³ occurs with likelihood ratio 3.7 for bacterial infection, and left shift (≥16% bands or absolute band count ≥1,500 cells/mm³) strongly indicates bacterial infection 1, 2, 3
Infections do not elevate RBC count: Instead, severe infections like sepsis are associated with anemia and changes in red cell distribution width (RDW), not increased red blood cell numbers 4, 5
Influenza specifically causes low WBC: In pediatric influenza A, WBC <4,000 cells/mm³ occurs in 27% of cases with lymphopenia, contradicting the pattern of elevated WBC 1
Infection-Associated Blood Count Changes
When infections do affect red blood cells, the changes are pathological rather than proliferative:
Eryptosis and hemolysis: Infections trigger premature red blood cell death through phosphatidylserine exposure, leading to anemia rather than erythrocytosis 1
RDW elevation: Sepsis causes increased red blood cell distribution width (baseline RDW elevation and further increases during hospitalization predict mortality), reflecting red blood cell damage and heterogeneity, not increased production 4, 5
Anemia in chronic infection: Autoimmune conditions like SLE cause accelerated eryptosis leading to reduced circulating RBCs and anemia, not erythrocytosis 1
Clinical Context for Dual Elevation
Polycythemia Vera Presentation
This myeloproliferative disorder causes:
- Erythrocytosis: Elevated hemoglobin/hematocrit from clonal RBC proliferation
- Leukocytosis: Often WBC 12,000-25,000 cells/mm³
- Thrombocytosis: Elevated platelet counts
- Splenomegaly: From extramedullary hematopoiesis
Other Myeloproliferative Neoplasms
Essential thrombocythemia and primary myelofibrosis can also show dual elevations, though less consistently than polycythemia vera.
Important Caveats
Relative polycythemia (hemoconcentration from dehydration) can occur with infection-related leukocytosis, but this represents decreased plasma volume rather than true erythrocytosis. The hematocrit is elevated but total red blood cell mass is normal or decreased 6.
Persistent inflammation-immunosuppression and catabolism syndrome (PICS) can cause prolonged leukocytosis (mean WBC 26.4K ± 8.8) in critically ill patients with tissue damage, but this is accompanied by anemia, not erythrocytosis 7.
Diagnostic Approach
When encountering simultaneous RBC and WBC elevation:
Measure absolute values: Confirm true erythrocytosis (elevated hemoglobin >16.5 g/dL in men, >16.0 g/dL in women) versus hemoconcentration 6
Assess for secondary causes: Rule out hypoxia-driven erythrocytosis (COPD, high altitude, sleep apnea) which would not typically cause leukocytosis
Evaluate for myeloproliferative neoplasm: Check JAK2 V617F mutation (positive in >95% of polycythemia vera), serum erythropoietin (low in polycythemia vera), and bone marrow biopsy if indicated 6
Consider clinical context: Infection causes leukocytosis but not true erythrocytosis; the combination strongly suggests clonal myeloid proliferation 1, 3, 6