Primary myelofibrosis
Description: any MPN leading to bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly
Epidemiology
Peak incidence is between 50 and 74 years of age.
Etiology
Pathophysiology
Genetic mutations → hyperplasia of atypical megakaryocytes → ↑ TGF-β → ↑ fibroblast activity → bone marrow obliteration due to fibrosis → displacement of hematopoietic stem cells → extramedullary hematopoiesis
Clinical features
- Constitutional symptoms
- Anemia
- Symptomatic splenomegaly
- Thromboembolic events
- Due to thrombocytosis and leukocytosis in the prefibrotic proliferative phase
- Petechial bleeding
- Increased infections
Myelofibrosis vs Aplastic anemia
- Myelofibrosis: splenomegaly
- Evidence of extra medullary hematopoesis
- Aplastic anemia: no
- Explanation: In myeloproliferative disorders like myelofibrosis, niche in marrow is disturbed by slow fibrosis of marrow so stem cells migrate and extra medullary haematopoiesis occurs. But in aplastic anemia (whether primary or secondary to drugs etc) stem cells themselves are destroyed or affected so haematopoiesis not possible anywhere. So we don't get hepatosplenomegaly and other evidences of extramedullary haematopoiesis.
Diagnostics
- CBC
- Classic presentation: anemia, thrombocytosis, and leukocytosis
- Patients may additionally present with:
- Thrombocytopenia (33%)
- Pancytopenia (10%)
- ↑ Leukocyte alkaline phosphatase, LDH
- Peripheral blood smear: dacrocytes (teardrop cells)
- JAK2 mutation
- Bone marrow studies
- Aspiration often fails (dry tap) because of severe marrow fibrosis.