What is the management for a patient with elevated red blood cell (RBC) and platelet count, also known as thrombocytosis and erythrocytosis?

Management of Elevated RBC and Platelet Count

Immediate Diagnostic Imperative

The combination of elevated RBC and platelet count strongly suggests polycythemia vera (PV), and you must immediately test for JAK2 mutation, obtain bone marrow morphology, and measure serum erythropoietin level to confirm the diagnosis. 1

The presence of both erythrocytosis and thrombocytosis is characteristic of PV rather than essential thrombocythemia (ET), where isolated thrombocytosis predominates. 2, 3 JAK2 mutation is expected in virtually all PV cases, and its absence combined with normal or increased serum erythropoietin makes PV unlikely. 3

Risk Stratification Framework

Once PV is confirmed, immediately stratify the patient into risk categories based on two critical factors:

• High-risk: Age >60 years OR history of thrombosis 1, 2
• Low-risk: Age ≤60 years AND no thrombosis history 1, 2

Advanced age (>60 years) and prior thrombosis are the most consistent and validated risk factors for recurrent thrombotic events. 1 Leukocytosis at diagnosis is associated with higher thrombosis and hemorrhage risk, though its prognostic significance may be limited to patients <60 years. 1

Critical caveat: Extreme thrombocytosis (platelets >1,000 × 10⁹/L) paradoxically increases bleeding risk through acquired von Willebrand syndrome (AvWS), not thrombosis risk. 1, 3 Screen for AvWS before starting aspirin if platelet count exceeds this threshold.

Mandatory Universal Treatment for All PV Patients

Phlebotomy

All patients with PV require phlebotomy to maintain hematocrit <45%, regardless of risk category. 2, 3 This target is non-negotiable and applies to both low-risk and high-risk patients. 1

Aspirin Therapy

Administer aspirin 81-100 mg once daily to all patients unless contraindications exist (active bleeding, AvWS, allergy). 1, 2 Some evidence suggests twice-daily dosing may be superior, though this requires further validation. 2

Cardiovascular Risk Factor Management

Aggressively manage all modifiable cardiovascular risk factors and counsel smoking cessation. 1

Cytoreductive Therapy Algorithm

High-Risk Patients (Age >60 or Thrombosis History)

High-risk patients require cytoreductive therapy in addition to phlebotomy and aspirin. 1, 2, 3

First-line agent: Hydroxyurea 1, 2

• Standard cytoreductive drug of choice
• Use cautiously in patients <40 years due to theoretical leukemogenic concerns 1

Second-line agents (for hydroxyurea intolerance or resistance):

• Interferon-α (including peginterferon alfa-2a or alfa-2b) 1
  • Preferred for younger patients
  • Preferred for pregnant patients requiring cytoreduction 1
  • Preferred for patients who defer hydroxyurea 1
• Busulfan 1, 2

Third-line consideration:

• Ruxolitinib: Reserved exclusively for severe protracted pruritus or marked splenomegaly unresponsive to hydroxyurea, interferon, or busulfan 1, 2, 3
• FDA-approved for PV with inadequate response to or intolerance of hydroxyurea 1

Low-Risk Patients (Age ≤60 and No Thrombosis History)

Low-risk patients require only phlebotomy and aspirin; cytoreductive therapy is NOT routinely indicated. 1, 2

Indications to initiate cytoreduction in low-risk patients:

• New thrombotic event 1
• Acquired von Willebrand disease with major bleeding 1
• Symptomatic or progressive splenomegaly 1
• Progressive disease-related symptoms (pruritus, night sweats, fatigue) 1
• Poorly tolerated phlebotomy regimen 1
• Progressively increasing leukocyte count 1

Definition of Hydroxyurea Intolerance/Resistance

Switch to second-line therapy when patients demonstrate:

• Inadequate hematologic response despite adequate dosing 1
• Development of cytopenias at necessary doses 1
• Documented intolerance per established criteria 1

Special Clinical Scenarios

Thrombotic Events

• Initiate clinically appropriate anticoagulation (LMWH, direct oral anticoagulant, or warfarin) per ACCP guidelines 1
• Assess need for cytoreductive therapy if not already receiving it 1
• Intensify or switch cytoreductive therapy if disease inadequately controlled 1
• Duration depends on thrombosis severity (abdominal vein thrombosis requires longer treatment than DVT) 1

Bleeding Complications

• Rule out and treat coexisting causes 1
• Withhold aspirin until bleeding controlled 1
• Normalize platelet counts with cytoreductive therapy 1
• Screen for acquired von Willebrand disease, especially with elevated platelet count, splenomegaly, or unexplained bleeding 1
• Consider GI consultation for unexplained GI bleeding with splenomegaly (evaluate for portal hypertension and gastric varices) 1

Surgery

• Emergency surgery: Proceed as necessary with close postoperative surveillance 1
• Elective surgery: Achieve near-normalization of CBC without prohibitive cytopenias before high-risk procedures (orthopedic, cardiovascular) 1
• Extended LMWH prophylaxis for high venous thromboembolism risk procedures (cancer surgery, splenectomy, orthopedic, cardiovascular) 1
• Consider aspirin prophylaxis following vascular surgery 1

Monitoring and Follow-Up

Monitor for:

• Thrombotic or hemorrhagic complications 1
• Disease-related symptoms requiring intervention 1
• Leukemic transformation (occurs in <10% at 20 years) 2
• Fibrotic transformation (post-PV myelofibrosis) 1
• Adverse prognostic mutations (ASXL1, SRSF2, IDH2) associated with inferior survival 3

Important note: Response criteria exist primarily for clinical trials; clinical benefit may not reach IWG-MRT thresholds, so assess based on symptom improvement at clinician discretion. 1