Skip to main content

Saturn Medic

Clinical Subject Page

Myelofibrosis (MF)

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm (MPN) characterized by abnormal megakaryocyte proliferation, progressive bone marrow fibrosis, ineffective hematopoiesis, and extramedullary hematopoiesis. It commonly causes anemia, constitutional symptoms, and splenomegaly

Also called

Primary Myelofibrosis

ICD-10

D47.4

Specialty

Hematology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

Myelofibrosis (MF) is a clonal myeloid disorder in which abnormal megakaryocytes release fibrogenic cytokines, causing progressive scarring of the bone marrow. Normal blood-cell production becomes impaired, resulting in anemia and other cytopenias. The body compensates by producing blood cells outside the bone marrow, especially in the spleen and liver, causing marked splenomegaly.

Etiology & Risk Factors

Myelofibrosis (MF) results from an acquired clonal abnormality of hematopoietic stem cells, commonly involving:

  • JAK2
  • CALR
  • MPL

-Risk Factors

  • Increasing age
  • Male sex
  • Previous myeloproliferative neoplasm
  • Previous Polycythemia Vera (PV)
  • Previous Essential Thrombocythemia (ET)
  • Rare familial predisposition

Pathophysiology

Clonal mutation in hematopoietic stem cells → abnormal megakaryocyte proliferation → release of fibrogenic cytokines such as TGF-β and PDGF → progressive bone marrow fibrosis → ineffective hematopoiesis → anemia and other cytopenias → extramedullary hematopoiesis in the spleen and liver → massive splenomegaly and hepatomegaly → progressive bone marrow failure and possible transformation to AML.

Clinical Presentation

-Symptoms

  • Fatigue

  • Weakness

  • Weight loss

  • Fever

  • Night sweats

  • Early satiety

  • Abdominal fullness

  • Left upper quadrant discomfort

  • Bone pain

  • Dyspnea

-Signs

  • Massive splenomegaly

  • Hepatomegaly

  • Pallor

  • Cachexia

  • Petechiae or bruising

  • Signs of anemia

History Taking

-Ask about:

  • Fatigue
  • Weight loss
  • Fever
  • Night sweats
  • Abdominal fullness
  • Early satiety
  • Bone pain
  • Bleeding
  • Previous thrombosis
  • Previous PV or ET

Physical Examination

-General Examination

Look for:

  • Pallor

  • Weight loss

  • Cachexia

  • Petechiae

  • Ecchymoses

-Abdominal Examination

Assess for:

  • Massive splenomegaly

  • Hepatomegaly

-Additional Examination

Look for:

    • Signs of anemia

    • Bleeding manifestations

    • Lymphadenopathy (uncommon)

Investigations

Complete Blood Count (CBC)

Typical findings:

  • Anemia

  • Variable leukocyte count

  • Variable platelet count

  • Thrombocytopenia in advanced disease

  • Pancytopenia in severe disease

Peripheral Blood Film

Characteristic findings:

  • Teardrop cells (dacrocytes)

  • Leukoerythroblastic picture

  • Nucleated RBCs

  • Immature granulocytes

  • Abnormal platelets

Bone Marrow Aspiration & Biopsy

Typical findings:

  • Dry tap on aspiration

  • Hypercellularity in early disease

  • Megakaryocytic proliferation and atypia

  • Increased reticulin/collagen fibrosis

Molecular Testing

  • JAK2 mutation

  • CALR mutation

  • MPL mutation

Additional Investigations

  • LDH

  • Uric acid

  • Renal function

  • Liver function

  • Abdominal ultrasound or CT for splenomegaly

  • Cytogenetic testing

-Prognostic Assessment

Risk assessment may use:

    • DIPSS

    • DIPSS-Plus

    • MIPSS70

Diagnosis

-Diagnosis is based on:

  • Bone marrow biopsy showing megakaryocytic proliferation and fibrosis
  • JAK2, CALR, or MPL mutation when present
  • Characteristic peripheral blood findings
  • Splenomegaly and constitutional symptoms
  • Exclusion of other myeloid neoplasms
Home / Home / Clinical Cases / Hematology System Clinical Cases / Myelofibrosis (MF)
Related Topics

Management

-Asymptomatic / Low-Risk Disease

  • Observation

  • Regular CBC and clinical monitoring

-Symptomatic Disease

  • Ruxolitinib

  • Fedratinib in selected patients

  • Treatment of anemia

  • Blood transfusions when required

-Anemia Management

  • Erythropoiesis-stimulating agents in selected patients

  • Transfusion support

  • Other anemia-directed therapy depending on the cause

-Severe Splenomegaly

  • JAK inhibitor therapy

  • Splenectomy in selected patients

  • Splenic irradiation rarely

-Curative Treatment

  • Allogeneic hematopoietic stem cell transplantation (HSCT)

Complications

  • Severe anemia
  • Massive splenomegaly
  • Hepatomegaly
  • Portal hypertension
  • Extramedullary hematopoiesis
  • Recurrent infections
  • Bleeding
  • Thrombosis
  • Bone marrow failure
  • Acute Myeloid Leukemia (AML) transformation

Prognosis

Prognosis varies according to disease risk, age, blood counts, symptoms, cytogenetic abnormalities, and molecular mutations. Some patients have an indolent course for many years, while high-risk disease may progress rapidly. Transformation to AML is associated with a poor prognosis.

Key Points / Clinical Pearls

  • Myelofibrosis (MF) is a myeloproliferative neoplasm.
  • Common mutations: JAK2, CALR, and MPL.
  • Abnormal megakaryocytes cause progressive bone marrow fibrosis.
  • Massive splenomegaly is characteristic.
  • Peripheral blood shows teardrop cells and a leukoerythroblastic picture.
  • Bone marrow aspiration may produce a dry tap.
  • Bone marrow biopsy confirms fibrosis.
  • Ruxolitinib is commonly used for symptomatic disease.
  • Allogeneic HSCT is the only potentially curative treatment.
  • MF can progress to bone marrow failure or AML.
  • Thapa B, Fazal S, Parsi M, Rogers HJ. National Center for Biotechnology Information (NIH). Myeloproliferative Neoplasms, StatPearls.
  • Kuykendall AT, Shah S, Talati C, et al. Myelofibrosis in 2019: Moving Beyond JAK2 Inhibition. Blood Cancer J. 2019;9:74. Blood Cancer Journal.
  • JAK2, CALR, and MPL Mutation Profiles in BCR-ABL Negative Myeloproliferative Neoplasms, a Referral Center Experience in the Middle East. PMC8085288.
  • Grinfeld J, Nangalia J, Baxter EJ, et al. Classification and Personalized Prognosis in Myeloproliferative Neoplasms. N Engl J Med. 2018;379:1416-1430.
  • MedlinePlus, National Library of Medicine (NIH). Myelofibrosis: Medical Encyclopedia.