What is the management approach for patients with elevated hematocrit (Hct) and thrombocytosis (elevated platelet count)?

Management of Elevated Hematocrit and Thrombocytosis

Immediate Priority: Rule Out Polycythemia Vera

The most critical first step is to evaluate for polycythemia vera (PV), a myeloproliferative neoplasm that requires specific management to prevent life-threatening thrombotic complications. 1, 2

Essential Diagnostic Workup

• Test for JAK2 mutation immediately - this is present in virtually all PV cases and its absence makes the diagnosis unlikely 2, 3, 4
• Measure serum erythropoietin level - normal or increased levels combined with absent JAK2 mutation effectively excludes PV 3, 4
• Obtain bone marrow biopsy with morphology assessment, as this remains the cornerstone of diagnosis 2
• Screen for additional driver mutations (CALR, MPL) if JAK2 is negative, as these may indicate other myeloproliferative neoplasms 2, 3
• Perform complete genetic assessment including ASXL1 and SRSF2 for prognostic stratification 1

If Polycythemia Vera is Confirmed

Immediate Thrombosis Prevention Strategy

All PV patients must maintain hematocrit below 45% through phlebotomy, as this is the single most important intervention to prevent thrombotic events. 1, 2, 4

The CYTO-PV trial demonstrated that maintaining hematocrit <45% versus 45-50% reduced cardiovascular death and major thrombosis from 9.8% to 2.7% (HR 3.91,95% CI 1.45-10.53) 1. This represents strong evidence that higher hematocrit targets are dangerous.

Phlebotomy Protocol

• Induction phase: Remove 300-450 ml weekly or twice weekly until hematocrit <45% is achieved 1
• Maintenance phase: Continue same volume per phlebotomy, with intervals determined by hematocrit levels 1
• Never allow hematocrit to exceed 45% - this threshold is non-negotiable 1, 2

Aspirin Therapy

• Initiate low-dose aspirin 81 mg once daily in all patients unless contraindications exist 1, 2, 4
• Screen for acquired von Willebrand syndrome before starting aspirin if platelet count exceeds 1,000 × 10⁹/L 3, 4

Risk Stratification for Cytoreductive Therapy

High-risk patients (age >60 years OR prior thrombosis history) require cytoreductive therapy in addition to phlebotomy and aspirin. 1, 2, 4

Additional indications for cytoreduction include: 1

• Poor tolerance to phlebotomy
• Symptomatic or progressive splenomegaly
• Severe disease-related symptoms
• Platelet count >1,500 × 10⁹/L
• Leukocyte count >15 × 10⁹/L

First-Line Cytoreductive Therapy

• Hydroxyurea is the first-line agent at any age, though use cautiously in young patients 1, 2, 4
• Recombinant interferon-alpha (rIFNα) is an equally acceptable first-line option 1, 2, 4
• Second-line options include busulfan or switching between hydroxyurea and interferon 2, 4
• Ruxolitinib should be reserved for severe protracted pruritus or marked splenomegaly unresponsive to standard therapy 2, 4

Cardiovascular Risk Management

• Aggressively manage all cardiovascular risk factors including hypertension, diabetes, hyperlipidemia, and smoking 1
• Recent data suggest JAK2V617F mutation and cardiovascular risk factors are additional thrombosis risk factors beyond age and history 3, 4

If Reactive (Secondary) Thrombocytosis

Reactive thrombocytosis does not require cytoreductive therapy unless platelet count exceeds 1,500 × 10⁹/L or thrombotic/hemorrhagic symptoms develop. 5

Key Distinguishing Features

• Platelet counts in reactive thrombocytosis are typically <1,500 × 10⁹/L 5
• Risk of thrombosis is NOT increased when platelets are <1,500 × 10⁹/L 5
• Common causes include iron deficiency, inflammation, infection, malignancy, post-surgical state, and blood loss 5

Management Approach

• Treat the underlying cause - this is the primary intervention 5
• Initiate low-dose aspirin (81-100 mg daily) once bleeding risk has decreased, but only if platelets remain <1,500 × 10⁹/L 5
• Use standard thromboprophylaxis (low molecular weight heparin) for high-risk situations like major surgery 5
• Avoid cytoreductive agents (hydroxyurea, anagrelide) regardless of platelet count, as these have significant adverse effects and are not indicated for reactive thrombocytosis 5

When to Refer to Hematology

• Immediate referral if platelet count exceeds 1,500 × 10⁹/L at any time 5
• Refer if cause of thrombocytosis remains unclear after initial workup 6, 7
• Refer if thrombotic or hemorrhagic symptoms develop 5

Critical Pitfalls to Avoid

• Never allow hematocrit to remain above 45% in PV - this dramatically increases thrombotic risk 1, 2
• Do not assume elevated platelets alone indicate need for cytoreduction - the underlying diagnosis determines management 5, 2
• Extremely high platelet counts (>1,500 × 10⁹/L) paradoxically increase bleeding risk more than thrombosis risk due to acquired platelet dysfunction 5
• Do not use direct oral anticoagulants if platelets drop below 50 × 10⁹/L - use LMWH instead 6, 7
• In PV, platelet count elevation alone (when <1,500 × 10⁹/L) does not predict thrombotic events - hematocrit control is paramount 8, 2