Makindo Medical Notes Comprehensive Medical Encyclopedia | Education for Healthcare Professionals

Makindo Medical Notes "One small step for man, one large step for Makindo"
Download all this content in the Apps now Android App and Apple iPhone/Pad App

MEDICAL DISCLAIMER: The contents are under continuing development and improvements and despite all efforts may contain errors of omission or fact. This is not to be used for the assessment, diagnosis, or management of patients. It should not be regarded as medical advice by healthcare workers or laypeople. It is for educational purposes only. Please adhere to your local protocols. Use the BNF for drug information. If you are unwell please seek urgent healthcare advice. If you do not accept this then please do not use the website. Makindo Ltd.

Myelofibrosis

About

Anaesthetics and Critical Care

Obstetrics Gynaecology

Oncology

Ophthalmology

Oral Medicine and Dentistry

Statistics and Research

Stroke

Surgery

Toxicology

Trauma and Orthopaedics

Twitter

Urology

🩸 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. ⚠️ A minority of cases transform to acute myeloid leukaemia (AML).

📖 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: 60–70 years.
Can be primary or evolve secondarily from polycythaemia vera / essential thrombocythaemia.

🧬 Aetiology / Pathogenesis

Clonal proliferation of megakaryocytes → release of platelet-derived growth factor (PDGF) and TGF-β → marrow fibrosis.
Haematopoiesis shifts to spleen and liver → massive hepatosplenomegaly.
Mutations: JAK2 V617F (~50%), CALR (~30%), MPL (~10%).
Complications: anaemia, splenic infarction, portal hypertension, AML transformation (~10–20%).

🩺 Clinical Features

Constitutional symptoms: fever, night sweats, weight loss (“B symptoms”).
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.

🔍 Investigations

Classic finding = leukoerythroblastic blood film with “teardrop” poikilocytes. 🧐

FBC: anaemia; early stages → raised WCC and platelets; later → pancytopenia.
Blood film: teardrop cells, nucleated RBCs, immature granulocytes, giant platelets.
Bone marrow: “dry tap” (aspiration failure); trephine biopsy shows fibrosis.
Cytogenetics: no Philadelphia chromosome (distinguishes from CML).
Raised LDH and uric acid (cell turnover).
LAP score: normal or ↑ (low in CML).

🔎 Differential: Myelofibrosis vs CML

Myelofibrosis: marrow fibrosis, teardrop cells, splenomegaly, ↑/↓ LAP, no BCR-ABL.
CML: marked leucocytosis, basophilia, BCR-ABL fusion gene, ↓ LAP score.

💊 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: ~3–5 years (longer in indolent disease, shorter in aggressive forms).
Common causes of death: infection, haemorrhage, AML transformation.

📚 References

Cases — Myelofibrosis

Case 1 — 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 ×10⁹/L, platelets 80 ×10⁹/L. Blood film shows tear-drop poikilocytes (dacrocytes). Bone marrow aspirate is “dry tap”; trephine biopsy shows fibrosis. Diagnosis: Primary myelofibrosis.
Case 2 — 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 — 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 ×10⁹/L, platelets 600 ×10⁹/L. JAK2 mutation positive. Film shows tear-drop red cells, nucleated RBCs, and immature myeloid cells. Diagnosis: Myelofibrosis (proliferative phase, JAK2-positive).

Teaching Commentary 🌿

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).

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

Edit