What is the treatment for thrombocytosis with hydroxyurea (Hydrea)?

Treatment of Thrombocytosis with Hydroxyurea

Hydroxyurea is the first-line cytoreductive therapy for thrombocytosis in high-risk patients with essential thrombocythemia (ET) or polycythemia vera (PV), with a target platelet count below 400 x 10^9/L to reduce thrombotic complications. 1

Indications for Hydroxyurea Treatment

• Cytoreductive therapy with hydroxyurea is indicated in high-risk patients with ET or PV, including those:

  • Over 60 years of age 1
  • With history of thrombosis or hemorrhage 1
  • With platelet count >1,500 x 10^9/L (due to increased bleeding risk) 1

• In low-risk patients, hydroxyurea may be indicated when:

  • Platelet count exceeds 1,500 x 10^9/L 1
  • Progressive myeloproliferation develops (increasing splenomegaly) 1
  • Disease-related symptoms become uncontrolled 1

Dosing and Administration

• Initial dosing:

  • Standard starting dose: 15-20 mg/kg/day 2
  • For patients >80 kg: consider 2.5 g/day 1
  • For patients with renal impairment (CrCl <60 mL/min): reduce dose by 50% to 7.5 mg/kg/day 2

• Dose adjustments:

  • Titrate to achieve target platelet count <400 x 10^9/L 1
  • Maximum dose: typically 2-3 g/day 1, 3
  • In emergency situations with extreme thrombocytosis, higher doses (up to 3g/day) may be used temporarily 3

Monitoring Response

• Monitor complete blood counts at least weekly during initial therapy 2

• Once stabilized, monitor every 4-8 weeks 1

• Target response:

  • Platelet count <400 x 10^9/L 1
  • WBC count <10 x 10^9/L 1
  • Resolution of disease-related symptoms 1

• No routine monitoring of bone marrow response is needed for clinical follow-up 1

• Bone marrow examination is indicated only when assessing for transformation to myelofibrosis or acute leukemia 1

Treatment Efficacy

• Hydroxyurea effectively reduces platelet counts to <500 x 10^9/L within 8 weeks in 80-86% of patients with ET or PV 4
• Reduces thrombotic complications compared to no treatment (3.6% vs 24% thrombotic events) 5
• Control of disease-related symptoms is achieved within 1 year in approximately 78% of patients 4

Resistance and Intolerance

Resistance or intolerance to hydroxyurea is defined by the following criteria:

For Essential Thrombocythemia:

• Platelet count >600 x 10^9/L after 3 months of adequate hydroxyurea dosing 1
• Platelet count >400 x 10^9/L with hemoglobin <10 g/dL at any dose 1
• Platelet count >400 x 10^9/L with WBC <2.5 x 10^9/L at any dose 1
• Presence of leg ulcers or other unacceptable mucocutaneous manifestations 1
• Hydroxyurea-related fever 1

For Polycythemia Vera:

• Need for phlebotomy to maintain hematocrit <45% despite 3 months of hydroxyurea 1
• Uncontrolled myeloproliferation (platelet count >400 x 10^9/L AND WBC >10 x 10^9/L) 1
• Failure to reduce splenomegaly by >50% 1
• Cytopenia at lowest effective dose (ANC <1.0 x 10^9/L, platelets <100 x 10^9/L, or Hb <10 g/dL) 1
• Presence of leg ulcers or other unacceptable toxicities 1

Second-Line Therapy Options

• For patients resistant or intolerant to hydroxyurea:

  • ET patients: anagrelide is the recommended second-line therapy 1
  • PV patients: interferon-alpha is the recommended second-line therapy 1
  • Ruxolitinib may be considered for patients with PV resistant or intolerant to hydroxyurea 1

• For extreme thrombocytosis requiring urgent intervention:

  • Therapeutic thrombocytapheresis may be used as a temporary measure while cytoreductive therapy takes effect 6

Important Considerations and Cautions

• Leukemogenic potential: Long-term use of hydroxyurea may increase risk of acute leukemia, particularly when combined with other cytotoxic agents 7

• Young patients (<40 years): Use hydroxyurea with caution due to long-term leukemogenic risk 1

• Acquired von Willebrand syndrome: Can occur with extreme thrombocytosis (>1,000 x 10^9/L), increasing bleeding risk 3

• Cardiovascular risk factors: Aggressively manage these in all patients with ET or PV 1

• Pregnancy: Consider interferon-alpha instead of hydroxyurea for pregnant patients requiring cytoreductive therapy 1

• Monitor for common side effects:

  • Myelosuppression (most common) 2
  • Mucocutaneous manifestations 1
  • GI symptoms 1
  • Leg ulcers 1