What is the initial management for an adult patient presenting with severe leukocytosis (elevated white blood cell count) and thrombocytosis (elevated platelet count)?

Management of Severe Leukocytosis and Thrombocytosis

Immediately obtain a peripheral blood smear and complete blood count with differential to distinguish between reactive and malignant causes, followed by urgent bone marrow aspiration and biopsy if acute leukemia is suspected, while simultaneously initiating aggressive intravenous hydration (2.5-3 liters/m²/day) if white blood cell count exceeds 100,000/μL. 1, 2

Immediate Diagnostic Priorities

Initial Laboratory Assessment

• Examine the peripheral blood smear immediately to identify blasts, dysplasia, immature granulocytes (left shift), basophilia, and assess for monomorphic versus pleomorphic cell populations 2, 3
• Quantify the degree of left shift, blast percentage, basophilia, and confirm the thrombocytosis on manual differential, as automated counts may be inaccurate 4, 2
• Check for Philadelphia chromosome/BCR-ABL by RT-PCR or FISH if chronic myeloid leukemia (CML) is suspected based on the combination of leukocytosis, thrombocytosis, basophilia, and splenomegaly 4
• Screen for JAK2V617F mutation to distinguish clonal from reactive thrombocytosis, as this mutation is present in 50-70% of essential thrombocythemia (ET) and polycythemia vera (PV) cases 5, 6

Urgent Bone Marrow Evaluation

• Perform bone marrow aspiration and biopsy immediately if blast percentage appears elevated (>5%) or if acute leukemia is suspected, as morphologic evaluation remains essential for definitive diagnosis despite molecular advances 1, 2, 7
• Do not delay diagnostic workup, but treatment can be safely postponed for several days in most cases to obtain complete molecular typing, except in symptomatic leukostasis 1

Emergency Management Based on Clinical Presentation

Symptomatic Leukostasis (Neurological, Respiratory, or Hypoxia Symptoms)

• Initiate emergency leukapheresis immediately if symptomatic leukostasis is present, coordinated with the start of definitive chemotherapy 1, 2
• Exception: Avoid leukapheresis in acute promyelocytic leukemia (APL) due to fatal hemorrhage risk 1, 2
• Start ATRA (all-trans retinoic acid) immediately if APL is suspected—do not wait for genetic confirmation given the high risk of hemorrhagic death 2

Hyperleukocytosis (WBC >100,000/μL) Without Leukostasis

• Begin aggressive intravenous hydration at 2.5-3 liters/m²/day to prevent tumor lysis syndrome 1
• Monitor frequently for tumor lysis syndrome with serial measurements of uric acid, potassium, phosphorus, calcium, and renal function 1
• Consider rasburicase for prevention of hyperuricemia and renal insufficiency in high-risk patients, though data are insufficient for a firm universal recommendation 1
• Initiate hydroxyurea 50-60 mg/kg/day for rapid cytoreduction as bridge therapy while awaiting definitive diagnosis 1, 2

Definitive Management Based on Diagnosis

Acute Myeloid Leukemia (AML)

• Begin induction chemotherapy with anthracycline plus cytarabine ("3+7" regimen) urgently once diagnosis is confirmed by bone marrow showing >20% blasts 8, 1, 2
• Perform echocardiography before anthracycline administration to assess cardiac risk factors 1
• Investigate for active infection with clinical examination and CT imaging, and consider delaying chemotherapy until infection is treated in patients planned for intensive treatment 1

Chronic Myeloid Leukemia (CML)

• Start imatinib 400 mg daily as first-line standard therapy once CML diagnosis is confirmed by Philadelphia chromosome or BCR-ABL positivity 4
• Use hydroxyurea for rapid cytoreduction if symptomatic leukocytosis or massive splenomegaly is present before or concurrent with imatinib initiation 8, 4
• Monitor complete blood counts weekly for the first month, biweekly for the second month, then every 2-3 months 9
• Target complete hematologic response defined as leukocyte count <10 × 10⁹/L and platelet count <450 × 10⁹/L with no immature cells in peripheral blood 8

Essential Thrombocythemia or Polycythemia Vera

• Risk stratify immediately: high-risk is defined by age >60 years or history of thrombosis; consider JAK2V617F mutation status and cardiovascular risk factors as additional thrombotic risk factors 5
• For high-risk patients, initiate hydroxyurea in addition to low-dose aspirin 5
• For low-risk patients, use low-dose aspirin alone for thrombosis prevention 5
• Screen for acquired von Willebrand syndrome before administering aspirin if platelet count exceeds 1,000 × 10⁹/L due to bleeding risk 5

Monitoring for Complications

Hematologic Toxicity

• If absolute neutrophil count falls below 1 × 10⁹/L and/or platelets below 50 × 10⁹/L during treatment, stop therapy until recovery to ANC ≥1.5 × 10⁹/L and platelets ≥75 × 10⁹/L, then resume at reduced dose 9

Fluid Retention

• Weigh patients regularly and monitor for signs of fluid retention, as severe fluid retention (pleural effusion, pericardial effusion, pulmonary edema, ascites) occurs in 1.3-6% of patients on imatinib 9
• Manage fluid retention with diuretics and supportive care; for significant pleural/pericardial effusion, consider dose interruption and short course of prednisone 20 mg daily for 3 days 8

Critical Pitfalls to Avoid

• Do not assume all cases are malignant—severe leukocytosis and thrombocytosis can represent leukemoid reactions secondary to infection or other reactive conditions 1, 3
• Never delay ATRA if APL is suspected, as this represents a hematologic emergency with high mortality from hemorrhage 2
• Do not perform leukapheresis in APL due to catastrophic bleeding risk 1, 2
• Perform HLA typing of patient and first- and second-degree relatives at diagnosis in patients who are candidates for allogeneic transplantation 1