What causes elevated white blood cell (WBC) count and elevated red blood cell (RBC) count?

Simultaneous Elevation of WBC and RBC: Key Causes and Evaluation

The most common causes of concurrent leukocytosis and erythrocytosis are polycythemia vera (a myeloproliferative neoplasm), chronic hypoxia-driven secondary polycythemia with concurrent infection or inflammation, and smoking-related effects on both cell lines. 1, 2

Primary Myeloproliferative Disorders

Polycythemia vera (PV) is the most important diagnosis to exclude when both WBC and RBC counts are elevated simultaneously. 1

• PV is a clonal myeloproliferative disorder characterized by true increase in red blood cell mass, often accompanied by leukocytosis and thrombocytosis 1
• This represents a primary bone marrow disorder requiring urgent hematology referral 2
• Extreme leukocytosis (>100,000/mm³) with elevated RBC represents a medical emergency due to risk of cerebral infarction and hemorrhage 2, 3
• Splenomegaly and lymphadenopathy are red flags requiring immediate hematology consultation 2

Secondary Polycythemia with Concurrent Leukocytosis

Hypoxia-driven secondary polycythemia can coexist with leukocytosis when infection or inflammation is present. 1, 2

Chronic Hypoxic States:

• Chronic obstructive pulmonary disease (COPD) causes elevated RBC through chronic hypoxia and can simultaneously elevate WBC through chronic inflammation 4, 5
• Smoking causes both true polycythemia (from chronic carbon monoxide exposure) and persistent leukocytosis 1, 4
• High altitude residence or chronic lung disease with superimposed bacterial infection 1, 2

Concurrent Infection in Polycythemic Patients:

• Bacterial infections cause neutrophil-predominant leukocytosis with left shift (≥1,500 bands/mm³ has likelihood ratio of 14.5 for bacterial infection) 2, 4
• WBC counts ≥14,000 cells/mm³ or left shift (≥6% bands) strongly suggest bacterial infection even without fever 4
• Respiratory tract infections, urinary tract infections, and skin/soft tissue infections are most common 2

Physiological and Medication-Related Causes

Certain medications and physiological stressors can elevate both cell lines simultaneously. 2, 4

• Corticosteroid therapy causes leukocytosis (particularly neutrophilia) and can unmask or exacerbate underlying polycythemia 2, 4, 3
• Lithium therapy consistently causes leukocytosis (WBC <4,000/mm³ would be unusual) 2, 4
• Acute physical or emotional stress elevates WBC through catecholamine and cortisol release, while potentially unmasking relative polycythemia through plasma volume contraction 1, 2, 4
• Dehydration causes relative polycythemia (contracted plasma volume) with stress-induced leukocytosis 1

Critical Diagnostic Algorithm

Immediate Assessment:

1. Obtain complete blood count with manual differential to assess absolute neutrophil count, band forms (left shift), and RBC indices 2, 4
2. Assess for infection systematically: fever, localizing symptoms, signs of sepsis mandate evaluation for bacterial infection 2, 4
3. Review current medications: corticosteroids, lithium, beta-agonists 2, 4

Distinguish True from Apparent Polycythemia:

• Evaluate for plasma volume depletion: severe dehydration, diarrhea, vomiting, diuretic use 1
• Smoking history: smoker's polycythemia is real and resolves with cessation 1
• Clinical context: most factors causing relative polycythemia are clinically obvious and do not require red cell mass measurements 1

Red Flags Requiring Urgent Hematology Referral:

• Extreme leukocytosis (>100,000/mm³) represents medical emergency 2, 3
• Splenomegaly or lymphadenopathy 2
• Constitutional symptoms: fever, weight loss, bruising, fatigue suggesting hematologic malignancy 6, 3
• Concurrent abnormalities in platelet counts 3
• Persistent unexplained elevation on serial measurements 2, 4

Common Pitfalls to Avoid

• Do not overlook polycythemia vera when both cell lines are elevated—this is a clonal disorder requiring specific treatment 1
• Do not assume dehydration alone without considering primary bone marrow disorders, especially if elevation persists after rehydration 1
• Do not ignore smoking history—it causes both true polycythemia and persistent leukocytosis 1, 4
• Serial measurements are more informative than single values for persistent unexplained elevation 2, 4
• Normal WBC does not exclude bacterial infection in patients with polycythemia—sensitivity is low, particularly in elderly or immunosuppressed patients 4
• Do not over-interpret single mildly elevated values without clinical context—transient elevations occur with exercise, stress, or diurnal variations 2, 4