The Intern At Work: Internal Medicine When the Bone Marrow Breaks Down: Primary Myelofibrosis
Jan 25, 2026
A concise tour of bone marrow biology and what happens when it scars. A clear run-through of driver mutations and how they fuel abnormal blood production. Practical guidance on diagnosis, testing and imaging is covered. Risk stratification and curative transplant options are discussed. New and recently approved therapies, including the JAK inhibitor story, are reviewed.
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Mutation-Driven Marrow Fibrosis
- Primary myelofibrosis is a clonal myeloproliferative neoplasm driven by JAK2, CALR, or MPL mutations and JAK-STAT overactivation.
- Excess megakaryocyte activity stimulates fibroblasts to produce collagen, causing marrow fibrosis and extramedullary hematopoiesis.
Stabilize And Screen Systematically
- Assess stability first: check GCS, ABCs, and vitals before further workup.
- Screen thoroughly for constitutional symptoms, bleeding, infections, thrombosis history, and hepatosplenomegaly on exam.
Key Labs And Mandatory Biopsy
- Order CBC with differential, hemolysis labs, LFTs, LDH, uric acid, CRP/ESR, and peripheral smear.
- Request a bone marrow core biopsy (expect dry tap sometimes) and send molecular and cytogenetic testing for JAK2/CALR/MPL.