PMF arises due to genetic mutations in bone marrow stem cells, but the cause of these changes is unknown.


The clinical signs and symptoms of PMF include:

  • Cytopenia including severe anaemia
  • Hepatosplenomegaly
  • Fatigue
  • Night sweats
  • Fever
  • Bone pain
  • Pruritus

Complications include bleeding, thrombosis, and progression to acute leukaemia, the latter occurring in approximately 20% of patients.


Clinical and laboratory parameters are assessed according to the 2016 World Health Organisation (WHO) diagnostic criteria, which distinguish a pre-fibrotic and an overtly fibrotic stage of the disease.

All of the following major criteria for must be met for diagnosis of PMF:

  • Typical megakaryocyte changes accompanied by reticulin/collagen fibrosis (≥ grade 2 for overtly fibrotic PMF and ≤ grade 1 for pre-fibrotic PMF)
  • Presence of JAK2, CALR or MPL mutations, or presence of other clonal markers, or absence of evidence for reactive bone marrow fibrosis
  • WHO criteria for other myeloid neoplasms not met

Additionally, one of the following minor WHO criteria must be met:

  • Unexplained anemia
  • Leukocytosis ≥ 11 × 109 /L
  • Palpable splenomegaly
  • Increased serum lactate dehydrogenase
  • A leukoerythroblastic blood smear (applies only for pre-fibrotic PMF)



Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021 Jan;96(1):145-162.

Arber DA, Orazi A, Hasserjian R et al.. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405.