What medical conditions can cause elevated white and red blood cell counts?

Medical Conditions Causing Simultaneous Elevation of White and Red Blood Cells

Polycythemia vera is the most critical diagnosis to exclude when both WBC and RBC counts are elevated simultaneously, as it represents a clonal myeloproliferative disorder requiring urgent hematology referral. 1, 2

Primary Myeloproliferative Disorders (Most Important)

Polycythemia Vera is characterized by:

• JAK2V617F mutation present in >95% of cases 2
• Trilineage myeloproliferation affecting red cells, white cells, and platelets 2
• Hemoglobin >18.5 g/dL (men) or >16.5 g/dL (women) with concurrent WBC elevation 2
• Subnormal serum erythropoietin levels (distinguishes from secondary causes) 2
• Requires bone marrow examination showing hypercellularity with trilineage growth 2

Critical pitfall: Do not assume dehydration alone when both cell lines are elevated—this is a clonal disorder requiring specific treatment and carries thrombotic risk. 1

Secondary Polycythemia with Reactive Leukocytosis

Chronic Hypoxic Conditions:

• Chronic obstructive pulmonary disease (COPD) causes elevated RBC through chronic hypoxia and simultaneously elevates WBC through chronic inflammation 1
• Cyanotic congenital heart disease produces compensatory erythrocytosis with concurrent reactive leukocytosis from chronic hypoxemia 2
• Chronic smoking causes true polycythemia from carbon monoxide exposure plus persistent leukocytosis 1

Key distinction: Secondary polycythemia shows normal or elevated erythropoietin levels and absence of JAK2 mutation. 2

Medication-Induced Causes

Corticosteroid therapy:

• Causes leukocytosis (particularly neutrophilia) 1, 3
• Can unmask or exacerbate underlying polycythemia 1
• Associated with higher WBC counts in hospitalized patients 4

Lithium therapy:

• Consistently causes leukocytosis (WBC <4,000/mm³ would be unusual) 1
• Listed as common medication associated with leukocytosis 3

Inflammatory and Metabolic Conditions

Adult-Onset Still's Disease (AOSD):

• Leukocytosis with striking neutrophilia (50% have WBC >15×10⁹/L, 37% have WBC >20×10⁹/L) 5
• Anemia of chronic disease that paradoxically can show reactive thrombocytosis 5
• Fever, rash, arthritis, and markedly elevated ferritin (4,000-30,000 ng/mL) 5

Metabolic Syndrome:

• Both platelet and white blood cell counts are elevated in patients with metabolic syndrome 6
• WBC increases progressively with number of metabolic syndrome risk factors 6
• Body mass index, diabetes, chronic kidney disease, and COPD associated with higher WBC counts 4

Diagnostic Algorithm

Immediate evaluation required:

1. Obtain complete blood count with manual differential to assess absolute neutrophil count, band forms, and RBC indices 1
2. Check JAK2V617F mutation if both cell lines persistently elevated 2
3. Measure serum erythropoietin level to distinguish primary from secondary polycythemia 2
4. Assess for splenomegaly (moderate or massive suggests alternative diagnosis beyond simple polycythemia vera) 2

If JAK2 positive or splenomegaly present:

• Urgent hematology referral for bone marrow examination with flow cytometry and cytogenetic testing 1, 2
• Evaluate for thrombotic risk factors 2

If JAK2 negative:

• Evaluate for chronic hypoxemia (pulse oximetry, arterial blood gas, chest imaging) 1
• Review medication list for corticosteroids, lithium, beta-agonists 1, 3
• Assess for infection systematically (fever, localizing symptoms, signs of sepsis) 1
• Consider AOSD if fever, rash, arthritis, and markedly elevated ferritin present 5

Critical Management Points

For confirmed polycythemia vera with elevated WBC:

• Phlebotomy to reduce thrombotic risk 2
• Cytoreductive therapy (hydroxyurea) when WBC >12×10⁹/L with controlled hematocrit 2

Common pitfall to avoid: Overlooking polycythemia vera when both cell lines are elevated, as this requires specific treatment beyond simple observation. 1 The presence of persistent elevation after rehydration mandates consideration of primary bone marrow disorders. 1