What is the most likely diagnosis for a patient with leukocytosis (white blood cell count), neutrophilia (absolute neutrophil count), anemia (low hemoglobin and hematocrit), and thrombocytosis (elevated platelet count)?

Differential Diagnosis: Infection vs. Inflammatory vs. Hematologic Disorder

The most likely diagnosis is an active bacterial infection, given the combination of leukocytosis (WBC 12.43), marked neutrophilia (ANC 9.94), anemia (Hgb 10.5), and thrombocytosis (platelets 530), which collectively point to an acute inflammatory/infectious process rather than a primary hematologic malignancy. 1, 2

Immediate Diagnostic Priority: Rule Out Bacterial Infection

The laboratory pattern strongly suggests bacterial infection based on established likelihood ratios:

• Absolute neutrophil count of 9.94 K/μL represents significant neutrophilia, and when WBC exceeds 10 × 10⁹/L (as in this case at 12.43), it carries a likelihood ratio of 3.7 for bacterial infection 1, 3
• The neutrophil percentage is approximately 80% (9.94/12.43), which approaches the threshold of >90% that carries a likelihood ratio of 7.5 for bacterial infection 1, 2
• Critical next step: Obtain a manual differential count (not automated) to assess for band forms and calculate absolute band count—if ≥1,500 cells/mm³, this carries the highest likelihood ratio (14.5) for documented bacterial infection 1, 3
• A left shift (≥16% bands) has a likelihood ratio of 4.7 for bacterial infection, even with only mild WBC elevation 1, 2

Secondary Findings Supporting Infection

The combination of anemia (Hgb 10.5, Hct 34.8) and thrombocytosis (platelets 530) strongly supports an infectious/inflammatory etiology:

• Infection is the most common cause of secondary thrombocytosis, accounting for nearly half of all cases in one large series of 801 patients 4
• Clinical and laboratory characteristics associated with infectious thrombocytosis include neutrophilia, leukocytosis, and anemia—all present in this patient 4
• The anemia likely represents anemia of chronic disease/inflammation, which is normocytic-normochromic and commonly accompanies active infection 5

Mandatory Workup to Identify Infection Source

Obtain these tests immediately:

• Blood cultures if any fever, chills, or systemic symptoms are present 1, 3
• Urinalysis with culture for urinary tract infection, particularly if dysuria, flank pain, or costovertebral angle tenderness exists 3
• Chest X-ray if any respiratory symptoms (cough, dyspnea, pleuritic pain) are present 1
• C-reactive protein or ESR to quantify inflammatory burden 2, 3
• Focused examination for specific infection sites: respiratory tract, urinary tract, skin/soft tissue, gastrointestinal tract, and in patients with cirrhosis, consider spontaneous bacterial peritonitis 1, 2

Alternative Diagnoses to Consider (Lower Priority)

Adult-Onset Still's Disease (AOSD)

• AOSD presents with marked leukocytosis and neutrophilia: 50% of patients have WBC >15×10⁹/L, and this patient's WBC of 12.43 is below that threshold 5, 2
• AOSD typically presents with high spiking fevers, salmon-pink rash, arthritis, sore throat, and extremely elevated ferritin (often >4,000 ng/mL and up to 250,000 ng/mL) 5
• Thrombocytosis is common in AOSD, but the diagnosis requires clinical features beyond laboratory findings alone 5

Chronic Myeloid Leukemia (CML)

• CML is unlikely because this patient's WBC (12.43) is far below the typical presentation of CML, where WBC often exceeds 100 × 10⁹/L 5
• CML chronic phase is associated with <15% blasts, basophilia, eosinophilia, and splenomegaly in 40-50% of cases 5
• About 50% of CML patients are asymptomatic at diagnosis, but the degree of leukocytosis here is insufficient for CML 5
• If CML is suspected, diagnosis requires cytogenetics showing t(9;22)(q34;q11) and BCR-ABL1 transcripts by RT-PCR 5

Iron Deficiency Anemia with Reactive Changes

• Severe iron deficiency can cause extreme thrombocytosis and leukocytosis, though this is quite exceptional 6
• The anemia here (Hgb 10.5) is moderate, not severe, making this less likely 6
• Check iron studies: serum iron, TIBC, ferritin, and transferrin saturation to exclude iron deficiency 5

Myeloproliferative Neoplasms

• Primary bone marrow disorders should be suspected when WBC counts are extremely elevated (>100,000/mm³) or when concurrent abnormalities in RBC or platelet counts suggest clonal disease 7
• This patient's WBC of 12.43 does not reach the threshold for hyperleukocytosis emergency 2, 7
• Weight loss, bleeding, bruising, hepatosplenomegaly, or lymphadenopathy would increase suspicion for marrow disorder 7

Critical Pitfalls to Avoid

• Do not ignore neutrophilia when total WBC is only mildly elevated—left shift can occur with normal or near-normal WBC and still indicate serious bacterial infection 1, 2
• Do not assume the absence of infection based on moderate WBC elevation—bacterial infections can present with variable WBC counts, particularly in elderly or immunosuppressed patients 2
• Do not rely on automated differential alone—manual differential is essential to assess band forms and immature granulocytes 1, 3
• Do not overlook thrombocytosis as a clue to infection—it is often dismissed but represents an important diagnostic finding when combined with neutrophilia and anemia 4
• Do not delay evaluation if any signs of sepsis develop (fever ≥38.3°C, hypotension, tachycardia, altered mental status)—mortality increases with each hour of delay in septic patients 1

Clinical Context Matters

Essential clinical information needed to refine the diagnosis:

• Presence of fever (single temperature ≥38.3°C or sustained ≥38.0°C for ≥1 hour markedly increases probability of bacterial infection) 1
• Localizing symptoms: cough, dysuria, abdominal pain, diarrhea, skin lesions 1, 2
• Recent surgery, trauma, or hospitalization 3
• Medication history: corticosteroids, lithium, beta-agonists can cause leukocytosis 2, 7
• Chronic conditions: cirrhosis (risk of spontaneous bacterial peritonitis), diabetes, immunosuppression 1, 2