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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Characteristic Percent or median result (range)
Age 49.8 (17-98)
Sex, percent female 66
Hemoglobin (g/dL) 13.7 (9.1-16.8)
WBC count (x 10(3)/microL) 9.0 (4.1-25.2)
Platelet count (x 10(3)/microL) 1000 (454-3460)
Palpable splenomegaly, percent 34.7
Asymptomatic, percent 45.3
Vasomotor symptoms, percent 13.3
History of fetal loss (women only), percent 11.2
History of thrombosis, percent 21.3
History of hemorrhage, percent 9.3
Normal cytogenetics, percent 87.4
JAK2 mutation, percent 48.7
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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