Clinical meaning
Myelofibrosis is a myeloproliferative neoplasm characterized by clonal hematopoietic stem cell proliferation that triggers reactive bone marrow fibrosis, displacing normal hematopoietic tissue and causing extramedullary hematopoiesis (compensatory blood cell production in the spleen and liver). The most common driver mutations are JAK2 V617F (65%), CALR (25%), and MPL (5%), all of which constitutively activate the JAK-STAT signaling pathway, promoting megakaryocyte proliferation. Abnormal megakaryocytes release fibrogenic cytokines (TGF-beta, PDGF, bFGF) that stimulate reticulin and collagen deposition by marrow fibroblasts, progressively replacing the marrow space. Clinical manifestations include massive splenomegaly (from extramedullary hematopoiesis, often extending below the umbilicus), constitutional symptoms (fatigue, night sweats, weight loss, fever from elevated cytokines), anemia (marrow failure and splenic sequestration), and leukoerythroblastic blood smear (teardrop cells, nucleated red blood cells, immature myeloid forms). The nurse monitors CBC for progressive cytopenias, assesses spleen size (risk of splenic infarction and rupture), monitors for portal hypertension from hepatic extramedullary hematopoiesis, administers JAK inhibitors (ruxolitinib) as prescribed, manages transfusion-dependent anemia, monitors for transformation to acute myeloid leukemia, and supports patients through allogeneic stem cell transplant (the only curative option).