What is the diagnosis and treatment for a patient with leukocytosis (high White Blood Cell (WBC) count), thrombocytosis (high platelet count), anemia (low hemoglobin (Hb)), normal Mean Corpuscular Volume (MCV), and normal Mean Corpuscular Hemoglobin (MCH)?

Diagnostic Approach to High WBC, High Platelets, Low Hemoglobin with Normal MCV/MCH

This constellation of findings—leukocytosis, thrombocytosis, and normocytic anemia—most commonly represents either a reactive process (secondary to inflammation, infection, or tissue damage) or a primary myeloproliferative disorder, and requires immediate systematic evaluation to distinguish between these entities and guide appropriate management. 1

Initial Diagnostic Workup

Obtain the following tests immediately:

• Reticulocyte count to assess bone marrow response to anemia 1
• Peripheral blood smear to evaluate cell morphology, left shift, blast cells, and toxic granulations 1, 2
• Inflammatory markers: CRP, ESR to detect active inflammation 1
• Iron studies: serum ferritin, transferrin saturation to identify iron deficiency 1
• Differential white blood cell count with specific attention to basophils, eosinophils, and immature forms 1

Distinguishing Primary vs. Secondary Causes

Features Suggesting Secondary (Reactive) Thrombocytosis and Leukocytosis:

• Most common causes (87.7% of thrombocytosis cases): tissue damage (42%), infection (24%), malignancy (13%), chronic inflammation (10%) 3
• Anemia of chronic disease (ACD) with normal or low MCV/MCH in the setting of inflammation 1
• Elevated inflammatory markers (CRP, ESR, leukocyte count) 1
• Platelet count typically <1000 × 10⁹/L 3
• No splenomegaly on physical examination 3

Features Suggesting Primary Myeloproliferative Disorder:

• Higher platelet counts (often >1000 × 10⁹/L) 3
• Splenomegaly on physical examination 1, 4
• Left-shifted granulopoiesis with basophilia or eosinophilia 1
• Constitutional symptoms: fever, weight loss, night sweats 2
• History of thrombotic events (arterial or venous) 3, 5
• Leukocytosis is an independent risk factor for thrombosis in myeloproliferative disorders 5

Critical Next Steps Based on Peripheral Smear

If Blast Cells Present (≥15-20%):

Urgent hematology referral and bone marrow evaluation are mandatory 1

• Bone marrow aspirate and biopsy with morphology, cytogenetics (minimum 15 metaphases), and FISH 1
• Flow cytometry to define myeloid vs. lymphoid phenotype 1
• BCR::ABL1 testing by RT-PCR or FISH to exclude chronic myeloid leukemia (CML) 1
• Tyrosine kinase domain mutation analysis if CML suspected 1

If No Blasts but Left Shift with Basophilia:

Consider CML in chronic phase 1

• BCR::ABL1 fusion transcript testing (e13a2, e14a2, or rare variants) is diagnostic 1
• Cytogenetic analysis for Philadelphia chromosome (22q-) 1
• CML presents with leukocytosis, left-shifted myeloid maturation, basophilia, and thrombocytosis 1

If Reactive Appearance:

Focus on identifying underlying cause:

• Search for infection: blood cultures, imaging for occult abscess or pneumonia 2
• Evaluate for tissue damage: recent surgery, trauma, burns 3
• Screen for malignancy: age-appropriate cancer screening, CT imaging if indicated 3
• Assess for chronic inflammatory conditions: inflammatory bowel disease, rheumatologic disorders 1

Anemia Evaluation in This Context

The normocytic anemia with normal MCH requires specific attention:

• If ferritin <30 μg/L without inflammation: iron deficiency anemia 1
• If ferritin <100 μg/L with inflammation present: functional iron deficiency 1
• If reticulocytes low/normal: inadequate bone marrow response suggesting ACD or deficiency 1
• If reticulocytes elevated: consider hemolysis (check haptoglobin, LDH, bilirubin) 1

A high RDW despite normal MCV may indicate coexisting microcytosis and macrocytosis (e.g., iron deficiency plus B12/folate deficiency), which can mask each other 1

Management Priorities

If Hyperleukocytosis (WBC >100,000/μL):

Immediate intervention required to prevent leukostasis:

• Aggressive IV hydration at 2.5-3 liters/m²/day 6, 7
• Hydroxyurea 50-60 mg/kg/day to achieve 50% WBC reduction within 1-2 weeks 6, 7
• Monitor for tumor lysis syndrome: allopurinol or rasburicase prophylaxis 6
• Avoid leukapheresis in acute promyelocytic leukemia due to hemorrhage risk 6, 7

If Primary Myeloproliferative Disorder Confirmed:

Risk stratification determines treatment intensity:

• High-risk patients (age >60 or prior thrombosis) require cytoreductive therapy 8
• Hydroxyurea is first-line for controlling proliferative cells and reducing organomegaly 7
• Leukocytosis independently predicts thrombosis and should influence treatment decisions 5

If Secondary/Reactive Process:

Treat underlying cause:

• Infection: prompt empiric broad-spectrum antibiotics without waiting for cultures 7
• Iron deficiency: oral or IV iron replacement based on severity and inflammation 1
• Inflammatory conditions: disease-specific anti-inflammatory therapy 1

Common Pitfalls to Avoid

• Do not delay workup in patients with constitutional symptoms, splenomegaly, or very high counts (>1000 × 10⁹/L platelets or >100,000/μL WBC) 6, 7
• Do not assume reactive thrombocytosis is benign if other risk factors for thrombosis are present 3
• Do not overlook functional iron deficiency in inflammatory states where ferritin may be falsely elevated 1
• Do not perform bone marrow biopsy without peripheral smear review first unless acute leukemia strongly suspected 1
• Hematology consultation is appropriate if the cause remains unclear after initial workup or if primary bone marrow disorder suspected 1