Essential Thrombocytosis

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Essential Thrombocytosis

• AM Report
• Bridger Clarke
• 12/10/2007

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Essential Thrombocytosis

• Presence of a chronic nonreactive thrombocythemic
  state that is not accounted for by one of the
  other chronic myeloproliferative disorders
  chronic myelogenous leukemia (CML), polycythemia
  vera (PV), primary myelofibrosis (PMF).

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Epidemiology

• 2.5 new cases/100,000 population per year
• Approximately 6,000 people are diagnosed each
  year in the US.
• Female to male ratio of approximately 21
• Median age at diagnosis is 60 years

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Clinical Features of ET

• Up to one-half of patients with ET may be totally
  asymptomatic at presentation.
• The remaining patients may report "vasomotor"
  symptoms or manifest thrombohemorrhagic
  complications.

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Clinical Features of ET

• Vasomotor Symptoms
• Headache
• Lightheadedness
• Syncope
• Atypical chest pain
• Acral paresthesia
• Livedo reticularis
• Erythromelalgia (burning pain of the hands or
  feet associated with erythema and warmth)
• Transient visual disturbances (eg, amaurosis
  fugax, scintillating scotomata, ophthalmic
  migraine)

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Erythromelalgia
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Clinical Features of ET

• Thrombosis and Hemorrhage
• Stroke, transient ischemic attacks
• Retinal artery or venous occlusions
• Coronary artery ischemia
• Pulmonary embolism
• Hepatic or portal vein thrombosis
• Deep vein thrombosis
• Digital ischemia

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Diagnostic Criteria

• Platelet count gt600,000/microL
• Megakaryocytic hyperplasia on bone marrow
  aspiration and biopsy

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Diagnostic Criteria

• Absence of the Philadelphia chromosome
• Absence of infection, inflammation, and other
  causes for reactive thrombocytosis
• Normal red blood cell (RBC) mass or a hemoglobin
  concentration lt13 g/dL
• Presence of stainable iron in a bone marrow
  aspiration or 1 g/dL increase in hemoglobin
  concentration after a one month trial of oral
  iron therapy.

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JAK2 Mutation

• Approximately 50 percent of patients with ET have
  shown presence of the JAK2 V617F mutation

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Prognosis

• Most patients with ET enjoy a normal life
  expectancy without associated disease-related
  complications
• Risk factors for inferior survival
• Low hemoglobin level (lt12 g/dL in females and
  lt13.5 in males)
• Age 60 years
• Leukocyte count 15,000/microL
• Smoking, diabetes mellitus, prior venous
  thrombosis

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Disease Transformation

• Transformation into polycythemia vera, primary
  myelofibrosis, or acute myeloid leukemia (AML)
  occurs on the order of 1-4
• Risk factors for disease transformation
• Low hemoglobin level (lt12 g/dL in females, lt13.5
  in males)
• Platelet count 1,000,000/microL
• Increased age

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Treatment

• Low dose aspirin is the treatment of choice for
  vasomotor symptoms
• Hydroxyurea has been shown to reduce the risk of
  thrombosis
• Maintenance of the platelet count lt400,000/microL
  may be associated with further reduction in
  thrombotic risk

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Hydroxyurea

• Impairs DNA repair by inhibiting ribonucleotide
  reductase
• Varying degrees of neutropenia and megaloblastic
  anemia accompany the platelet-lowering effect of
  HU
• Rising MCV is indicative of appropriate drug
  action

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Anagrelide

• Inhibits platelet aggregation via platelet
  anti-cyclic AMP phosphodiesterase activity
• Interference with megakaryocyte proliferation and
  maturation, resulting in platelet underproduction
• Toxicity
• Related to the drug's direct vasodilatory and
  inotropic effects
• headache (34 percent), palpitations/tachycardia
  (23 percent), fluid retention (14 percent), and
  diarrhea (8 percent)

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The End