What conditions can cause an increase in white blood cells (leukocytosis) and platelet count (thrombocytosis) in an adult patient?

Conditions Causing Combined Leukocytosis and Thrombocytosis

The most important pathologies to consider when both white blood cells and platelets are elevated include myeloproliferative neoplasms (particularly essential thrombocythemia, polycythemia vera, and chronic myeloid leukemia), acute bacterial infections, and inflammatory conditions. 1, 2

Myeloproliferative Neoplasms (Primary Concern)

Essential thrombocythemia (ET) and polycythemia vera (PV) are the most common myeloproliferative neoplasms presenting with both thrombocytosis and leukocytosis. 2

Essential Thrombocythemia

• Characterized by marked thrombocytosis (often >450 × 10⁹/L) with concurrent leukocytosis in many patients 2
• JAK2 mutation is present in 50-70% of ET patients, which distinguishes clonal from reactive thrombocytosis 2
• Leukocytosis (WBC >9.5 × 10⁹/L) in ET patients increases thrombotic risk with a hazard ratio of 1.8 3
• The combination of leukocytosis and thrombocytosis significantly elevates arterial thrombosis risk (RR 1.45) 4

Polycythemia Vera

• PV presents with erythrocytosis, but also features leukocytosis, thrombocytosis, and splenomegaly 2
• Almost all PV patients harbor a JAK2 mutation 2
• Leukocytosis in PV is associated with increased thrombotic risk and shortened survival 2, 4

Chronic Myeloid Leukemia (CML)

• A rare subgroup of CML presents with marked thrombocytosis (>2,000 × 10³/µL) without significant leukocytosis (<12,000/µL), mimicking ET 5
• These atypical CML cases are distinguished by Philadelphia chromosome presence, despite ET-like presentation 5
• Most commonly affects young females with normal neutrophil alkaline phosphatase scores 5

Acute Bacterial Infections (Secondary Reactive Cause)

Bacterial infections commonly cause reactive leukocytosis with neutrophilia, and can produce concurrent reactive thrombocytosis. 1, 6

Diagnostic Markers for Bacterial Infection

• Absolute band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for documented bacterial infection 6, 7
• Neutrophil percentage >90% carries a likelihood ratio of 7.5 for bacterial infection 6
• Left shift (≥16% band neutrophils) has a likelihood ratio of 4.7 for bacterial infection, even with normal total WBC 6, 7
• Total WBC ≥14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 6

Specific Infections to Consider

• Respiratory tract infections, urinary tract infections, skin/soft tissue infections, and gastrointestinal infections commonly cause this pattern 6
• Clostridium difficile infection with leukocytosis ≥15,000 cells/mL indicates severe disease requiring vancomycin or fidaxomicin 1

Inflammatory and Other Reactive Causes

Thrombocytosis can occur as a reactive phenomenon alongside leukocytosis in various inflammatory states. 1

Risk Factors Associated with Both Elevations

• Malignancy can cause both leukocytosis and thrombocytosis as paraneoplastic phenomena 1
• Acute infections, autoimmune diseases, and critical illness can produce combined elevations 1
• Thrombocytosis (defined as elevated platelet count) is recognized as a VTE risk factor in medical inpatients 1

Critical Diagnostic Algorithm

Step 1: Assess for Acute Infection

• Obtain manual differential count to calculate absolute band count (most powerful predictor) 6, 7
• Evaluate for fever, focal infection signs (respiratory, urinary, skin/soft tissue, gastrointestinal) 6, 8
• Perform blood cultures if systemic infection suspected, site-specific cultures as indicated 6

Step 2: If Infection Excluded, Evaluate for Myeloproliferative Neoplasm

• Order JAK2V617F mutation testing—present in 50-70% of ET and nearly all PV cases 2
• Obtain peripheral blood smear to assess for immature myeloid cells, basophilia, and platelet morphology 2, 5
• Check BCR-ABL (Philadelphia chromosome) to exclude CML, especially in young females with extreme thrombocytosis 5
• Measure serum erythropoietin level—normal or increased excludes PV when JAK2 is absent 2

Step 3: Risk Stratification if Myeloproliferative Neoplasm Confirmed

• High-risk criteria: age >60 years OR history of thrombosis 2
• Additional risk factors: JAK2V617F mutation, cardiovascular risk factors, WBC >9.5 × 10⁹/L 2, 3
• Screen for acquired von Willebrand syndrome if platelet count >1,000 × 10⁹/L before starting aspirin 2

Important Caveats and Pitfalls

Do not assume reactive thrombocytosis without excluding clonal disorders—JAK2 mutation testing distinguishes reactive from clonal thrombocytosis. 2

Beware of spurious leukocytosis caused by platelet clumping—automated counters may miscount platelet clumps as WBCs, requiring blood smear verification. 9

Do not overlook atypical CML presenting as ET—check BCR-ABL even when clinical picture suggests ET, particularly in young females with extreme thrombocytosis. 5

Manual differential count is essential—automated analyzers cannot accurately assess band forms needed for infection diagnosis. 6, 7

In elderly patients with cardiovascular comorbidities, combined leukocytosis and thrombocytosis warrants aggressive evaluation for both infection and myeloproliferative disorders, as both significantly increase mortality risk. 8, 4