see also:

• thrombocytosis
• Janus kinase - STAT signalling

• a myeloproliferative disorder characterised by a high platelet count of > 600 × 10^3/µL for at least 2 months
• incidence ~ 20 new cases per 1 million population per year
• mainly effects middle aged and elderly
• similar to primary myelofibrosis, this condition is due to mutually exclusive acquired somatic gene mutations:
  • 40-50% of cases are associated with a mutation in the JAK2 kinase (V617F) gene
  • 25% of cases are associated with calreticulin gene CALR exon 10 mutation
  • 5-10% of cases are associated with MPL gene mutations
• rarely it may be inherited “Primary Hereditary Thrombocytosis” due to germline mutations which are mostly autosomal dominant ¹⁾ in either:
  • the thrombopoietin gene (THPO)
  • the thrombopoietin receptor gene (MPL) - include MPL-P106L, MPL-S505N (this may increase thrombotic risk), and MPL-W515R, as well as the polymorphism MPL-K39N termed MPL Baltimore
  • JAK2 kinase (V617F) gene - not inherited itself as this is a somatic mutation, but some families have familial predisposition
• prognosis is much better than for myelofibrosis with 10 yr survival rates > 90%, and 20 yr survival rates around 75% for JAK-2 or MPL mutations, and ~85% for CALR mutations
• patients are at risk of:
  • thrombosis (risk is ~ double for JAK-2 patients compared with MPL or CALR, being ~20% over 10yrs and 30% over ~20yrs)²⁾
  • haemorrhage
  • throbbing and burning of the hands and feet due to the occlusion of small arterioles by platelets (erythromelalgia)
  • splenomegaly
  • 3-4% evolve into AML
  • some develop myelofibrosis

• low dose aspirin is often advised to prevent thrombosis but there may be an increased risk of bleeding if aspirin is initiated while the platelet count is very high
• those at risk of complications or with very high platelet count, if not pregnant or lactating, consider either:
  • hydroxyurea
  • interferon-α
  • anagrelide - lower risk of DVT than with hydroxyurea but higher risk of arterial thrombus, severe bleeding and transformation to myelofibrosis
• in patients who have life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis