How should an adult with a white blood cell count of about 40 × 10⁹/L and a hemoglobin of 19 g/dL be evaluated and managed?

Urgent Evaluation for Polycythemia Vera and Myeloproliferative Neoplasm

This patient requires immediate hematology referral and workup for polycythemia vera (PV) or another myeloproliferative neoplasm, as the combination of marked leukocytosis (WBC 40.41 × 10⁹/L) and elevated hemoglobin (19.1 g/dL) strongly suggests a primary bone marrow disorder rather than a reactive process. 1, 2

Immediate Diagnostic Steps

Essential Laboratory Tests

• Order CBC with manual differential immediately to identify which white blood cell line is elevated, calculate absolute counts, and assess for left shift or immature forms 1
• Obtain peripheral blood smear review to examine WBC morphology, assess for blast cells, dysplastic features, or other malignant cells that would indicate acute leukemia 1
• Order comprehensive metabolic panel including BUN, creatinine, electrolytes, calcium, and LDH to monitor for tumor lysis syndrome and assess organ function 1

Critical Red Flags Present

• The hemoglobin of 19.1 g/dL exceeds the diagnostic threshold for PV (>16.5 g/dL in men, >16 g/dL in women), making this a major criterion for diagnosis 3
• The WBC of 40.41 × 10⁹/L represents marked leukocytosis that, when combined with elevated hemoglobin, strongly suggests a myeloproliferative disorder rather than reactive leukocytosis 4
• Immediate hematology referral is indicated because peripheral smear abnormalities, splenomegaly, or lymphadenopathy require urgent specialist evaluation 1

Why This Is Likely Polycythemia Vera

Diagnostic Reasoning

• PV classically presents with elevated hemoglobin and often concurrent leukocytosis, with approximately 30% of PV patients having WBC counts ≥11.0 × 10⁹/L 4
• The combination of these two elevated cell lines indicates trilineage proliferation, a hallmark of myeloproliferative neoplasms 3
• Reactive causes of leukocytosis (infection, inflammation, stress) do not cause sustained hemoglobin elevation to 19.1 g/dL 2, 5

Thrombotic Risk Assessment

• This patient faces significantly elevated thrombotic risk - WBC ≥11.0 × 10⁹/L in PV patients carries a hazard ratio of 1.87 (95% CI 1.44-2.43) for thrombotic events compared to WBC <7.0 × 10⁹/L 4
• Even WBC 8.5-11.0 × 10⁹/L increases thrombotic risk (HR 1.47), and this patient's WBC of 40.41 × 10⁹/L places them at extreme risk 4

Required Hematology Workup

Genetic and Bone Marrow Testing

• JAK2V617F mutation testing is mandatory - this mutation is present in >95% of PV cases and is a major diagnostic criterion 3
• Bone marrow aspirate and biopsy should be performed to assess for hypercellularity with trilineage growth (erythroid, granulocytic, and megakaryocytic proliferation) characteristic of PV 3
• Serum erythropoietin level should be measured - subnormal levels support PV diagnosis if JAK2 mutation is absent 3

Additional Testing

• Assess for splenomegaly on physical examination or imaging, as this is common in myeloproliferative neoplasms 3
• Screen for prior thrombotic events including unusual sites (portal vein, hepatic vein, splenic vein), as these may be the first presentation of masked PV 3

Urgent Management Considerations

Thrombosis Prevention

• Do not delay evaluation - patients with PV and leukocytosis have substantially increased thrombotic risk requiring prompt cytoreductive therapy 4
• Consider hydroxyurea (50-60 mg/kg/day) to reduce WBC count to <10-20 × 10⁹/L once PV diagnosis is confirmed, as this addresses both the elevated WBC and hemoglobin 6

Critical Pitfalls to Avoid

• Do not attribute the elevated hemoglobin to dehydration or hemoconcentration when WBC is also markedly elevated - this combination indicates a primary marrow process 3
• Do not assume this is reactive leukocytosis from infection - reactive processes do not cause hemoglobin of 19.1 g/dL 2, 5
• Do not delay referral waiting for symptoms - asymptomatic patients with these laboratory values still require urgent hematology evaluation, as thrombotic events may be the first clinical manifestation 3
• Do not overlook the need for thrombosis screening - investigate for prior unusual site thromboses (portal, hepatic, splenic veins) even if the patient is currently asymptomatic 3

Prognosis and Risk Stratification

• Patients with JAK2-positive PV presenting with leukocytosis have poorer prognosis, particularly in older age groups 3
• The degree of leukocytosis correlates directly with thrombotic risk - this patient's WBC of 40.41 × 10⁹/L places them in the highest risk category 4