Related Subjects:
|Iron deficiency Anaemia
|Haemolytic anaemia
|Macrocytic anaemia
|Megaloblastic anaemia
|Microcytic anaemia
|Myelodysplasia
|Myelofibrosis
๐ฉธ Primary myelofibrosis is a myeloproliferative neoplasm where bone marrow is progressively replaced by fibrous tissue (reticulin and collagen).
This leads to ineffective haematopoiesis, extramedullary haematopoiesis, and massive splenomegaly. โ ๏ธ
A minority of cases transform to acute myeloid leukaemia (AML).
๐ About
- One of the BCR-ABL negative myeloproliferative neoplasms (alongside polycythaemia vera and essential thrombocythaemia).
- Characterised by marrow fibrosis, abnormal megakaryocyte proliferation, and extramedullary haematopoiesis.
- Median age of onset: 60โ70 years.
- Can be primary or evolve secondarily from polycythaemia vera / essential thrombocythaemia.
๐งฌ Aetiology / Pathogenesis
- Clonal proliferation of megakaryocytes โ release of platelet-derived growth factor (PDGF) and TGF-ฮฒ โ marrow fibrosis.
- Haematopoiesis shifts to spleen and liver โ massive hepatosplenomegaly.
- Mutations: JAK2 V617F (~50%), CALR (~30%), MPL (~10%).
- Complications: anaemia, splenic infarction, portal hypertension, AML transformation (~10โ20%).
๐ฉบ Clinical Features
- Constitutional symptoms: fever, night sweats, weight loss (โB symptomsโ).
- Massive splenomegaly (often palpable well below costal margin).
- Hepatomegaly (extramedullary haematopoiesis).
- Anaemia-related symptoms: fatigue, dyspnoea.
- Bone pain (marrow expansion / fibrosis).
- Complications: infections, gout (hyperuricaemia), thrombosis, bleeding.
๐ Investigations
Classic finding = leukoerythroblastic blood film with โteardropโ poikilocytes. ๐ง
- FBC: anaemia; early stages โ raised WCC and platelets; later โ pancytopenia.
- Blood film: teardrop cells, nucleated RBCs, immature granulocytes, giant platelets.
- Bone marrow: โdry tapโ (aspiration failure); trephine biopsy shows fibrosis.
- Cytogenetics: no Philadelphia chromosome (distinguishes from CML).
- Raised LDH and uric acid (cell turnover).
- LAP score: normal or โ (low in CML).
๐ Differential: Myelofibrosis vs CML
- Myelofibrosis: marrow fibrosis, teardrop cells, splenomegaly, โ/โ LAP, no BCR-ABL.
- CML: marked leucocytosis, basophilia, BCR-ABL fusion gene, โ LAP score.
๐ Management
- Supportive: transfusions, folate, allopurinol (prevent gout).
- Hydroxycarbamide: reduces splenomegaly and blood counts.
- JAK2 inhibitors (e.g., ruxolitinib): reduce symptoms and splenomegaly.
- Splenectomy / irradiation: palliative for massive splenomegaly.
- Allogeneic stem cell transplant: only curative option; reserved for younger patients with high-risk disease.
- Median survival: ~3โ5 years (longer in indolent disease, shorter in aggressive forms).
- Common causes of death: infection, haemorrhage, AML transformation.
๐ References
Cases โ Myelofibrosis
- Case 1 โ Splenomegaly and Cytopenia:
A 68-year-old man presents with weight loss, night sweats, and early satiety. Exam: massive splenomegaly. FBC: Hb 9.0 g/dL, WCC 4.0 ร10โน/L, platelets 80 ร10โน/L. Blood film shows tear-drop poikilocytes (dacrocytes). Bone marrow aspirate is โdry tapโ; trephine biopsy shows fibrosis. Diagnosis: Primary myelofibrosis.
- Case 2 โ Post-Polycythaemia Vera Myelofibrosis:
A 72-year-old woman with a 12-year history of polycythaemia vera now develops progressive anaemia, night sweats, and bone pain. Spleen is palpable 12 cm below costal margin. Bloods: pancytopenia with leukoerythroblastic film. Diagnosis: Secondary myelofibrosis following PV.
- Case 3 โ Young Adult with Constitutional Symptoms:
A 40-year-old man presents with severe fatigue, weight loss, and bone pain. FBC: Hb 10.5 g/dL, WCC 18 ร10โน/L, platelets 600 ร10โน/L. JAK2 mutation positive. Film shows tear-drop red cells, nucleated RBCs, and immature myeloid cells. Diagnosis: Myelofibrosis (proliferative phase, JAK2-positive).
Teaching Commentary ๐ฟ
Myelofibrosis is a myeloproliferative neoplasm where clonal proliferation of haematopoietic stem cells leads to cytokine-driven bone marrow fibrosis. Blood film shows a leukoerythroblastic picture with tear-drop RBCs. Patients often have constitutional symptoms (fever, sweats, weight loss), massive splenomegaly (extramedullary haematopoiesis), and cytopenias. Mutations: JAK2, CALR, MPL. Prognosis is variable, with risk of transformation to AML. Management:
- Supportive (transfusions, hydroxycarbamide for cytoreduction),
- JAK inhibitors (ruxolitinib) for splenomegaly/symptoms,
- Allogeneic stem cell transplantation in fit younger patients (curative option).
