Myelofibrosis (MF)

Myelofibrosis (MF) is a hematological disorder characterized by bone marrow fibrosis and extramedullary hematopoiesis (EMH).^1,2 MF can develop on its own, as primary MF, or it can develop as a complication of other diseases, such as polycythemia vera (PV) or essential thrombocythemia (ET). These secondary cases are known as post-PV MF and post-ET MF.¹ 

Myelofibrosis occurs more frequently in men than in women, and patients are typically diagnosed around 65 years of age.^2,3 In the United States, MF is estimated to affect less than 50,000 individuals.⁴ More than 20% of patients are asymptomatic, and diagnosis is often discovered through an abnormal blood count or a peripheral blood smear revealing leukoerythroblastosis.²

Constitutional symptoms, such as fever, weight loss, night sweats, and pruritus, are the clinical hallmarks of this disease. These symptoms are most likely linked to abnormal cytokine production, and they can be severe in many patients, requiring management. Typical clinical manifestations of MF also include anemia, hepatomegaly, splenomegaly, cytopenia, and abdominal symptoms.^2,3

Complications of MF can include disease progression to acute leukemia (in up to 20% of patients), thrombohemorrhagic events, organ failure, and infections, which frequently lead to premature death.^2,3 

Anemia and Thrombocytopenia

The progressive bone marrow fibrosis observed in MF leads to worsening cytopenias, specifically thrombocytopenia and anemia. Anemia is the most common laboratory finding in MF, as approximately 50% of patients with primary MF present with hemoglobin levels below 10 mg/dL. The presentation of white blood cell and platelet counts is variable.³

Anemia in MF often leads to fatigue, weakness, palpitations, dyspnea, bone pain, and compensatory tachycardia. It may also support the development of tissue hypoxia-related symptoms and impact pulmonary function in patients with lung disease.²

Thrombocytopenia and the ensuing effects are common complications in patients with MF. Because of patients’ low blood platelet count, bleeding of any grade and severity can occur. Thrombohemorrhagic events are among the main causes of death in patients with MF.² 

Read more about MF signs and symptoms

Extramedullary Hematopoiesis and Hepatosplenomegaly

Extramedullary hematopoiesis can affect various organs and tissues, including the spleen, liver, lymph nodes (leading to lymphadenopathy), serosal surfaces (leading to ascites or pleural effusion), and epidural spaces (leading to nerve or spinal cord compression).² 

Musculoskeletal complaints deriving from EMH include osteosclerosis, hypertrophic osteoarthropathy, and periostitis.² When EMH involves the central nervous system, intracranial hypertension may develop, which may lead to chronic headaches, delirium, gait instability, papilledema, photophobia, alterations in the level of consciousness, and, though uncommon, coma, paralysis, or death. When affecting the gastrointestinal tract, EMH can exacerbate existing abdominal pain or obstructions of the intestinal lumen.²

Splenomegaly in MF results from the splenic sequestration of immature myeloid cells and leads to fatigue, which is the most common symptom experienced by patients.^2,3 A palpable spleen has been observed in over 80% of patients with MF.² Abdominal fullness, early satiety, and left upper quadrant pain can also result from splenomegaly. Acute left upper quadrant pain may develop from spontaneous splenic infarction.³ 

Read more about MF diagnosis

Extramedullary hematopoiesis can also affect the liver, causing hepatomegaly in up to 65% of patients with MF. Hepatomegaly can lead to abnormal liver function tests, coagulopathies, and increased abdominal complaints.²

Potential complications from hepatosplenomegaly include portal hypertension (observed in approximately 7% of patients with MF) and variceal bleeding, which may lead to massive hemorrhage.^2,3

Read more about MF complications

References

1. Tremblay D, Mascarenhas J. Next generation therapeutics for the treatment of myelofibrosis. Cells. 2021;10(5):1034. doi:10.3390/cells10051034

2. Mughal TI, Vaddi K, Sarlis NJ, Verstovsek S. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. Int J Gen Med. 2014;7:89-101. doi:10.2147/IJGM.S51800

3. Abdel-Wahab OI, Levine RL. Primary myelofibrosis: update on definition, pathogenesis, and treatment. Annu Rev Med. 2009;60:233-245. doi:10.1146/annurev.med.60.041707.160528

4. Primary myelofibrosis. National Organization for Rare Disorders (NORD). Accessed December 29, 2022.

Reviewed by Kyle Habet, MD, on 12/31/2022.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.