Management of Leukocytosis with Elevated Hemoglobin/Hematocrit and Low ESR
This patient requires immediate evaluation for a primary myeloproliferative neoplasm, most likely polycythemia vera or chronic myeloid leukemia, given the combination of leukocytosis (WBC 5.91), erythrocytosis (hemoglobin 16.6, hematocrit 50.9), and absence of inflammatory markers (low ESR, no fever).
Initial Diagnostic Approach
The absence of fever and low ESR effectively rules out infectious or inflammatory etiologies that typically present with leukocytosis. 1, 2 In bacteremia and febrile infections, ESR is elevated in 73.2% of cases and CRP is elevated in over 98% of bacteremic episodes. 3, 4 The combination of leukocytosis with polycythemia (elevated hemoglobin and hematocrit) without inflammatory markers is pathognomonic for myeloproliferative disorders rather than reactive processes. 5, 6
Critical Immediate Steps
Obtain peripheral blood smear immediately to assess for basophilia, left shift, immature granulocytes, and blast percentage. 5, 6 The presence of basophilia strongly suggests chronic myeloid leukemia, while its absence with isolated erythrocytosis points toward polycythemia vera. 5
Check for splenomegaly on physical examination. 5 The combination of leukocytosis and splenomegaly immediately raises suspicion for chronic myeloid leukemia, which classically presents with myeloid hyperplasia, splenomegaly, neutrophil leukocytosis, thrombocytosis, and basophilia. 5
Order BCR-ABL testing via RT-PCR or FISH from peripheral blood if CML is suspected based on smear findings or splenomegaly. 5 The Philadelphia chromosome t(9;22) or BCR-ABL fusion gene is present in almost all CML patients. 5
Algorithmic Diagnostic Workup
If Peripheral Smear Shows Left Shift or Basophilia:
Proceed directly to BCR-ABL testing and bone marrow biopsy. 5 Do not delay if blast percentage is elevated (>5%), as this may indicate accelerated phase CML or transformation to acute leukemia. 1
If BCR-ABL is positive: Diagnose chronic myeloid leukemia and initiate imatinib 400 mg daily as first-line therapy. 5 Consider hydroxyurea for rapid cytoreduction if symptomatic leukocytosis or massive splenomegaly is present. 5
If Peripheral Smear Shows Mature Neutrophils Without Left Shift:
Measure JAK2 V617F mutation, serum erythropoietin level, and arterial oxygen saturation. Low or normal erythropoietin with elevated hemoglobin/hematocrit and positive JAK2 mutation confirms polycythemia vera. 5
Perform bone marrow biopsy to assess for hypercellularity with trilineage proliferation (erythroid, granulocytic, and megakaryocytic hyperplasia). 5
Key Differentiating Features
Polycythemia vera presents with isolated erythrocytosis and leukocytosis without basophilia, normal to low ESR (due to increased red cell mass), and JAK2 mutation positivity in >95% of cases. 5, 6
Chronic myeloid leukemia presents with leukocytosis, basophilia, left shift with immature granulocytes, splenomegaly in 50-90% of cases, and BCR-ABL positivity. 5 Approximately 50% of CML patients are asymptomatic at diagnosis. 5
Common Pitfalls to Avoid
Do not attribute leukocytosis to infection in the absence of fever and elevated inflammatory markers. 2, 3 Fever is present in 78.4% of bacteremic episodes, and CRP is elevated in 98.4%. 3 The absence of both makes infection highly unlikely.
Do not delay bone marrow biopsy if blast percentage is >5% on peripheral smear. 1 This requires immediate evaluation for acute leukemia, where induction chemotherapy should include an anthracycline and cytosine arabinoside. 1
Do not confuse reactive leukocytosis with myeloproliferative neoplasms. 6, 7 Reactive processes show toxic granulations, Döhle bodies, and activated neutrophil changes on peripheral smear, which are absent in myeloproliferative disorders. 6
Management Based on Final Diagnosis
If CML is Confirmed:
Start imatinib 400 mg daily immediately. 5 This is the first-line standard therapy for chronic phase CML. 5
Use hydroxyurea for rapid cytoreduction if WBC >100,000/μL or symptomatic splenomegaly is present before imatinib takes effect. 5
If Polycythemia Vera is Confirmed:
Initiate phlebotomy to maintain hematocrit <45% in men and <42% in women to reduce thrombotic risk.
Consider hydroxyurea or interferon-alpha for cytoreduction if high-risk features are present (age >60 years or prior thrombosis).
If Acute Leukemia is Suspected:
Emergency leukapheresis is recommended for symptomatic leukocytosis. 1, 5 Patients with excessive leukocytosis at presentation may require emergency leukapheresis prior to induction chemotherapy. 1
Start ATRA immediately if acute promyelocytic leukemia (APL) is suspected—do not wait for genetic confirmation. 5 APL induction chemotherapy should include an anthracycline and ATRA. 1