Essential Thrombocytosis (Primary Thrombocythemia) Treatment

What is Essential Thrombocytosis?

Essential thrombocytosis is a myeloproliferative disorder characterized by an elevated platelet count without a secondary explanation. The disease is caused by clonal proliferation of platelets in the bone marrow, likely related to certain genetic mutations (e.g., JAK2). About 50% of individuals are asymptomatic during diagnosis – these patients are incidentally found to have an elevated platelet count on routine CBC (complete cell count). Other patients may experience symptoms such as headache, dizziness, or visual changes. Woman are more often affected with the disease than men.

Additional symptoms may occur due to complications of the disease, such as hemorrhage or thrombosis. Thrombosis can result in devastating conditions such as heart attack, stroke, or pulmonary embolism. Occasionally, patients with progress to leukemia or develop myelofibrosis. Due to the importance of this condition, it is critical that patients understand its causes, symptoms, and treatment. By the end of this article, you will have the answers to these essential questions:

What causes Essential Thrombocytosis?

Essential thrombocytosis is a clonal stem cell disease that results in excessive platelet production. The precise cause is uncertain, although there are severe key genetic mutations (including JAK2) closely associated with the disease. The presence of these mutations on genetic testing help determine prognosis and guide treatment.

The majority of cases of essential thrombocytosis are sporadic, not familial. There is some evidence to suggest that the disease is related to an increased sensitivity of circulating hematopoietic progenitor cells to thrombopoeitin. Thrombopoeitin is the hormone that stimulates platelet production in the bone marrow. Occasionally, essential thrombocytosis can be complicated by leukemia or myelofibrosis.

Reactive thrombocytosis is defined as thrombocytosis that occurs due to an underlying medical condition. This form of thrombocytosis is not clonal and is much more prevalent than essential thrombocytosis. Conditions such resulting in systemic inflammation, infection, and iron deficiency are common causes of secondary thrombocytosis.

How common is Essential Thrombocytosis?

Essential thrombocytosis is a relatively uncommon myeloproliferative disorder that is often incidentally detected by your primary care doctor. The condition often requires referral to a hematology and oncology specialist for consideration of bone biopsy.

The incidence of essential thrombosis is approximately 1-2.5 per 100,000 people per year. The prevalence of the disease is about 9-24 cases per 100,000 people. Women are also twice as likely to be affected by the disease than men. The mean age at diagnosis of essential thrombocytosis is 60 years.

What are the symptoms and signs of Essential Thrombocytosis?

Essential thrombocytosis is asymptomatic in approximately 50% of individuals and often discovered incidentally during a routine complete blood count (CBC) showing thrombocytosis (elevated platelet count). Patients with symptoms often experience the following:

  • Headache
  • Dizziness
  • Visual changes

Individuals may also develop symptoms related to complications of the disease, including:

  • Thrombosis – stroke, heart attack, deep vein thrombosis, pulmonary embolism
  • Hemorrhage – intracranial or gastrointestinal bleeding
  • Spontaneous abortion

How is Essential Thrombocytosis diagnosed?

Essential thrombocytosis is based on 4 criteria set by the World Health Organization. These criteria include a platelet count ≥450,000/microL. Bone marrow biopsy showing megakaryocyte proliferation – megakaryocytes are platelet cell precursors. An absence of significant neutrophilia or erythropoiesis. The diagnosis of other myeloproliferative disorders must not be met and specific mutations (e.g., JAK2) or clonal markers should also be demonstrated in the blood. There may be no other identifiable cause for the thrombocytosis such as infection, inflammation, or iron deficiency.

Commonly ordered blood tests include a CMP (comprehensive metabolic panel), CBC (complete blood cell count) with peripheral blood smear, and urine analysis. Patients with headache, dizziness, and visual changes will also typically be checked for abnormal thyroid function (e.g., TSH, free T4). Neuroimaging with head CT or brain MRI may also be necessary in some cases to exclude stroke or brain tumor. Your doctor may also want to assess the electrical activity of your heart with an electrocardiogram (EKG).

How is Essential Thrombocytosis treated?

Most patients with essential thrombosis live a normal life-expectancy. General treatment measures include smoking cessation, weight loss, and optimization of cardiovascular risk factors (e.g., diabetes, hypertension, hyperlipidemia).

Treatments available for essential thrombocytosis are not curative but may help prevent complications such as bleeding or thrombosis, and can alleviate symptoms. Therapy depends on the individual’s risk for complications, which is determined based on factors such as age, history of thrombosis, and JAK2 mutation status. In general, treatment usually includes one of the following cytoreductive agents:

  • Hydrea (hydroxyurea)
  • Agrylin (anagrelide)
  • Interferon - preferred agent for use in pregnancy

These agents work by reducing the platelet count. Your doctor will normally try to achieve platelet concentration values between 100,000 to 400,000/microL. Patients are also often treated antiplatelet agents such as low-dose aspirin to prevent thrombosis and vasomotor symptoms.

Essential Thrombocytosis Patient Summary:

  • Essential thrombocytosis is a myeloproliferative disorder characterized by an elevated platelet count (≥450,000/microL) without a secondary explanation.
  • The disease is caused by clonal proliferation of platelets, likely related to certain genetic mutations (e.g., JAK2).
  • About 50% of individuals are asymptomatic during diagnosis – these patients are incidentally found to have an elevated platelet count on routine CBC (complete cell count). Other patients may experience as headache, dizziness, or visual changes.
  • Additional symptoms occur due to complications of the disease, such as hemorrhage or thrombosis. Occasionally, patients with progress to leukemia or develop myelofibrosis.
  • Most patients live a normal life-expectancy. General treatment measures include smoking cessation, weight loss, and optimization of cardiovascular risk factors.
  • Treatments available for essential thrombocytosis are not curative but may help prevent complications such as bleeding or thrombosis, and can alleviate symptoms.
  • In general, treatment usually includes one of the following cytoreductive agents: Hydrea (hydroxyurea), Agrylin (anagrelide), or Interferon (preferred for use in pregnancy).
  • These agents work by reducing the platelet count. Your doctor will normally try to achieve platelet concentration values between 100,000 to 400,000/microL.
  • Patients are also often treated antiplatelet agents such as low-dose aspirin to prevent thrombosis and vasomotor symptoms.

References:

  1. Barbui T, Finazzi G, Carobbio A, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 2012; 120:5128.
  2. Barbui T, Vannucchi AM, Buxhofer-Ausch V, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J 2015; 5:e369.
  3. Wolanskyj AP, Lasho TL, Schwager SM, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005; 131:208.

Popular Essential Thrombocytosis Medications

The above information is an educational aid only. It is not intended as medical advice for individual conditions or treatments. Talk to your doctor, nurse or pharmacist before following any medical regimen to see if it is safe and effective for you.