essential thrombocythemia

Etiology

• idiopathic

Epidemiology

• less common than secondary thrombocytosis
• 20% of patients with essential thrombocythemia are < 40 years of age

Genetics

• ~50% associated with JAK2 V617F mutation
• autosomal dominant form associated with defects in THPO

Clinical manifestations

• 2/3 of patients with essential thrombocytosis are asymptomatic
• arterial thrombosis
  • transient cerebral ischemia, syncope
  • digital ischemia
  • occlusion of coronary or mesenteric vessels
  • erythromelalgia
    • dysethesia of palms & soles
  • livedo reticularis
  • headache, visual symptoms
• venous thrombosis
  • portal vein
  • hepatic vein
  • splenic vein
• hemorrhage (50% of patients with essential thrombocytosis)
  • generally involves mucous membranes or skin
    • resembles von Willebrand's disease type 2
  • gastrointestinal hemorrhage
  • when platelet count > 1,000,000/uL
• splenomegaly (50%)
• hepatomegaly (20%)

Diagnostic criteria

• essential thrombocythemia
  • elevated platelet count (> 600,000/uL) on 2 different occasions separated by at least 1 month in connection with bone marrow findings
    • hypercellular bone marrow with morphologically abnormal megakaryocytic hyperplasia in connection with elevated platelet count
    • absence of Philadelphia chromosome
  • exclusion of secondary causes of thrombocytosis

Laboratory

• complete blood count (CBC)*
  • elevated platelet count (> 450,00-600,000/uL)
  • platelet count can exceed 1E06/uL for primary or secondary thrombocytosis
  • normal red cell volume (MCV)
  • hemoglobin < 13 g/dL
  • leukocyte count elevated in 1/2 of patients with essential thrombocythemia
  • basophilia may be noted
• impaired platelet aggregation response to:
  • epinephrine
  • collagen
  • adenosine diphosphate
• ristocetin cofactor activity (vWF)
  • low value is contraindication for aspirin
• hyperkalemia if platelets > 1E06/mm3
  • lysis of platelets or leukocytes during clot formation & retraction
  • determine plasma K+ rather than serum K+
• bone marrow biopsy
  • increase in megakaryocytes
  • presence of adequate iron
  • absence of collagen fibrosis
  • absence of Philadelphia chromosome or other bcl-abl gene rearrangements
• stem cell culture
  • spontaneous growth of megakaryocyte colony forming units in essential thrombocythemia
• JAK2 V627F mutation (50%)
• calreticulin (CALR) gene mutation
• thrombopoietin (MPL) receptor gene mutation

* case presented with normal platelet count

Complications

• risks for transformation to leukemia at 10, 20, & 30 years are 1%, 8%, & 24%, respectively
• risks for any myeloid transformation (leukemia, myelodysplastic syndrome, myeloid metaplasia, or polycythemia vera) are 9%, 28%, & 59%, respectively
  • treatment with cytoreductive drugs does not affect risk of myeloid transformation
• hemorrhagic complications
• arterial thrombosis &/or venous thrombosis occur in 20-30% of patients with essential thrombocythemia

Differential diagnosis

• iron deficiency
• hemorrhage
• cancer
• infection
• chronic inflammatory disease

Management

• asymptomatic patients younger than 60 years of age without history of thrombosis can be observed if platelet counts are < 1,000,000/uL
• indications for treatment*
  • patients > 60 years of age
  • platelet count > 1,000,000/uL
  • history of thrombosis
  • increased risk for thrombosis due to cardiovascular risk, i.e.hypertension, diabetes mellitus
• treatment
  • hydroxyurea 500-2000 mg QD + aspirin 81 mg QD
    • lowers risk of arterial thrombosis & bleeding regardless of platelet count achieved
  • anagrelide + aspirin may be less effective than hydroxyurea + aspirin in preventing thrombosis
  • interferon-alpha if pregnant
    • 3 million units SC
  • previous guideline: lower platelet count to < 400,000/uL
• smoking cessation
• control of platelet count, plateletpheresis
  • acute ischemic events
  • platelet count > 1,500,000/uL
• aspirin & dipyridamole are controversial
  • may lead to serious hemorrhage
  • may protect against thrombosis
  • aspirin 81 mg QD
    • indicated in patients with thrombosis despite adequate platelet count control
    • may be used to treat erythromelalgia
• platelet pheresis or platelet transfusion may be required with hemorrhage
• treat thrombosis with anticoagulation

* essential thrombocythemia discovered incidentally on routine health examination requires treatment if indications for treatment are satisfied despite a lack of guidelines for screening

More general terms

• thrombocytosis (thrombocythemia)