What causes elevated white and red blood cell counts?

Elevated White and Red Blood Cell Counts: Causes and Clinical Approach

The simultaneous elevation of both white blood cells (WBCs) and red blood cells (RBCs) most commonly occurs with hemoconcentration from dehydration, though infection with volume depletion, polycythemia vera, chronic hypoxia, or smoking can also cause this pattern.

Primary Mechanism: Hemoconcentration

Volume depletion is the most frequent cause of concurrent WBC and RBC elevation, as both cell lines become concentrated when plasma volume decreases 1. This occurs with:

• Dehydration from any cause (inadequate intake, vomiting, diarrhea, excessive sweating) 1
• Infection with volume depletion - bacterial infections cause true leukocytosis while concurrent dehydration concentrates both cell lines 2, 3
• Diuretic use leading to intravascular volume contraction 1

Infectious Causes of Leukocytosis

When infection is present, bacterial infection is the leading cause and should be your first consideration 2, 3. Key diagnostic markers include:

• Absolute band count ≥1,500 cells/mm³ (likelihood ratio 14.5 for bacterial infection) 4
• Neutrophil percentage >90% (likelihood ratio 7.5) 4
• Left shift ≥16% bands (likelihood ratio 4.7) - this can occur even with normal total WBC count 4, 5
• Total WBC ≥14,000 cells/mm³ 2

Critical pitfall: Normal WBC does not exclude bacterial infection, particularly in elderly or immunosuppressed patients 3, 4. Left shift with normal total WBC still indicates bacterial infection and warrants evaluation 5.

Common bacterial sources include respiratory tract infections, urinary tract infections, skin/soft tissue infections, and gastrointestinal infections 2, 4.

Physiological and Stress-Related Causes

Physical and emotional stress cause acute WBC elevation through catecholamine and cortisol release, mobilizing neutrophils from bone marrow storage pools 2, 3. This includes:

• Exercise (particularly intense or prolonged) 3
• Emotional stress, anxiety 3, 4
• Surgery, trauma, seizures 6, 7

Medication-Induced Leukocytosis

Corticosteroids are the most common medication cause 2, 4. Other culprits:

• Lithium consistently causes leukocytosis - WBC <4,000/mm³ would be unusual in lithium-treated patients 2, 3
• Beta-agonists 4, 6
• Epinephrine 4

Chronic Conditions Causing Persistent Elevation

• Smoking and obesity - associated with higher baseline WBC counts 2, 3
• Chronic inflammatory conditions including inflammatory bowel disease 2, 3
• Chronic hypoxia (COPD, high altitude, sleep apnea) - causes secondary polycythemia with elevated RBCs 6

Primary Hematologic Disorders

Polycythemia vera causes true elevation of RBC mass with frequent concurrent leukocytosis and thrombocytosis 6, 7. Suspect when:

• Persistent elevation without clear secondary cause
• Splenomegaly present 4
• Concurrent platelet abnormalities 7

Extreme leukocytosis (>100,000/mm³) represents a medical emergency due to risk of cerebral infarction and hemorrhage 4, 7.

Diagnostic Algorithm

1. Obtain CBC with manual differential to assess absolute neutrophil count, band forms, and immature cells 2, 3, 4

2. Assess clinical context systematically:

• Fever, localizing symptoms, signs of sepsis mandate infection evaluation 3, 4
• Volume status assessment (orthostatics, mucous membranes, skin turgor) 1
• Medication review: corticosteroids, lithium, beta-agonists 3, 4

3. Risk stratification based on WBC pattern:

• WBC ≥14,000 with left shift = high suspicion for bacterial infection 2, 3
• Left shift with normal WBC = still indicates possible bacterial infection 4, 5
• Isolated mild elevation without left shift = consider physiologic causes, medications, chronic conditions 2, 3

4. Consider additional testing if indicated:

• Blood cultures if fever or sepsis suspected 1, 4
• Site-specific cultures based on symptoms 1
• Repeat CBC after hydration to assess for hemoconcentration 1

Critical Pitfalls to Avoid

Do not overinterpret a single mildly elevated WBC without clinical context - transient elevations occur with exercise, stress, or diurnal variations 3, 4

Do not ignore high neutrophil percentage (>84%) when total WBC is normal - left shift can occur with normal WBC and still indicate bacterial infection 3, 4, 5

Do not assume absence of infection based on normal or low WBC - sensitivity is poor, especially in elderly patients 3, 4

Serial measurements are more informative than single values for persistent unexplained elevation 2, 3

In hospitalized patients without infection, malignancy, or immune dysfunction, WBC up to 14.5 × 10⁹/L may be normal - be cautious interpreting values between 11-14.5 8