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Symptoms

Myelofibrosis (MF) is a rare hematologic cancer affecting hematopoietic stem cells in the bone marrow. It is characterized by extensive scar tissue accumulation in the bone marrow, resulting in problems with normal blood cell production, including red blood cells, platelets, and white blood cells.^1,2

As normal blood cell production becomes increasingly affected, this leads to severe anemia, thrombocytopenia/thrombocytosis, and leukopenia/leukocytosis, each with their own respective signs and symptoms.^1,2

Anemia Signs and Symptoms

Anemia in MF is caused by bone marrow failure and splenic sequestration.³ Common signs and symptoms of anemia include^1,2:

Extreme fatigue
Weakness
Dyspnea
Pallor
Exercise/activity intolerance

Read more about MF complications

Thrombocytopenia Signs and Symptoms

Low platelet counts of less than 100×10⁹/L may occur in patients with primary or secondary MF, often predicting a poorer prognosis for the patient. Patients with MF with platelet counts below 50×10⁹/L demonstrate increased red blood cell transfusion dependence, higher blast counts, more severe anemia, and more unfavorable karyotypes.⁴ Signs and symptoms of thrombocytopenia include^1,2,5:

Easy bruising/ecchymosis/petechiae (20% of patients)
Easy bleeding or bleeding that does not stop quickly

Read more about MF prognosis

Thrombocytosis Signs and Symptoms

A small percentage of patients with essential thrombocythemia (ET) develop secondary MF. The initial phase of ET is characterized by thrombocytosis, or the production of too many platelets, with a high risk of vascular complications, including thrombosis. Patients with secondary MF from pre-existing ET (post-ET MF) also demonstrate these characteristics.⁶

Most symptoms accompanying thrombocytosis or thrombocythemia are secondary to an increased incidence of thrombosis, most commonly in the brain, hands, and feet.⁷These symptoms include⁷:

Chronic headaches, migraines, or dizziness (due to brain thrombosis)
Transient ischemic attacks, strokes, or seizures (extreme cases of brain thrombosis)
Confusion or altered speech (secondary to brain thrombosis)
Burning or throbbing pain/numbness/redness in the feet or hands (due to thromboses in these regions)
Chest pain
Shortness of breath (possible pulmonary embolism)
Nausea
Weakness
Complications with pregnancy

Another seemingly contradictory symptom of thrombocytosis is easier bruising/bleeding, especially in mucous membranes (nosebleeds, gingival bleeding, blood in feces). This symptom results from decreased numbers of platelets circulating in the peripheral blood after the formation of blood clots, leading to platelet deficiency and the inability to repair damage to blood vessel walls.⁷

Read more about MF types

Leukopenia Signs and Symptoms

While leukopenia (<4×10⁹/L) occurs the least frequently out of all the cytopenias in patients with MF, it is still a possible feature of certain MF phenotypes.⁸ Decreased white blood cell counts result in an increased risk of infection. Common signs and symptoms that may indicate leukopenia include²:

Frequent or recurrent infections
Fever

Read more about MF risk factors

Leukocytosis Signs and Symptoms

In contrast with leukopenia, leukocytosis is a sign of disease progression, both in MF and other underlying myeloproliferative neoplasms, such as polycythemia vera (PV), which may transform into secondary MF in its more advanced stages (post-PV MF). The presence of persistent leukocytosis predicts more aggressive disease progression and a worse prognosis.⁹Signs and symptoms of leukocytosis include¹⁰:

Fever
Fatigue
Pain
Dyspnea
Wheezing
Night sweats
Rash
Unexpected weight loss

Read more about MF life expectancy

Leukoerythroblastosis Signs and Symptoms

Leukoerythroblastosis, another common feature of MF, is one of the 5 possible minor criteria used to diagnose overtly fibrotic primary MF.¹¹ It develops in more advanced stages of overtly fibrotic MF, indicating the extent that bone marrow has been replaced with fibrotic scar tissue.A peripheral blood smear finding leukoerythroblastosis reveals nucleated red blood cells and immature white blood cells circulating in the peripheral blood.¹²

Read more about MF histology

Splenomegaly or Hepatomegaly Signs and Symptoms

Splenomegaly is another one of the 5 possible minor criteria used to diagnose primary MF.¹¹ It occurs in approximately 90% of patients with MF, and 35% of patients have a spleen that is easily palpated on examination. Hepatomegaly occurs in around 60% to 70% of patients with MF.⁵ Signs and symptoms include⁵:

Abdominal pain or discomfort
Feeling of subcostal fullness
Early satiety
Decreased appetite
Weight loss
Signs of portal hypertension (10% to 18% of patients)

Read more about MF diagnosis

Constitutional Signs and Symptoms

Constitutional symptoms are nonspecific, generalized symptoms that impact the general well-being or health status of a person.13 They may indicate infection, disease flares, or malignancy (especially if unexplained weight loss is present).14 Constitutional symptoms are believed to be cytokine-mediated, resulting in their widespread systemic effects.¹⁵

In addition to anemia, splenomegaly secondary to extramedullary hematopoiesis, and leukoerythroblastosis, constitutional symptoms are one of the hallmark features of MF.¹⁶ They include¹⁴:

Weight loss
Decreased appetite
Fever
Fatigue
Excessive night sweats
Bone or joint pain
Dyspnea
Intractable cough
Pruritus
Lymphadenopathy (10% to 20% of patients)⁵ or peripheral edema

Read more about MF clinical features

Other Signs and Symptoms

Gout occurs in 6% of patients with MF.⁵

Reduction of MF symptoms is the primary goal of treatment.²

Read more about MF treatment

References

Myelofibrosis. Mayo Clinic. June 8, 2021. Accessed December 16, 2022.
Myelofibrosis: signs and symptoms. Leukemia & Lymphoma Society. Accessed December 16, 2022.
Naymagon L, Mascarenhas J. Myelofibrosis-related anemia: current and emerging therapeutic strategies. Hemasphere. 2017;1(1):e1. doi:10.1097/HS9.0000000000000001
Masarova L, Alhuraiji A, Bose P, et al. Significance of thrombocytopenia in patients with primary and postessential thrombocythemia/polycythemia vera myelofibrosis. Eur J Haematol. 2018;100(3):257-263. doi:10.1111/ejh.13005
Lal A. Primary myelofibrosis clinical presentation: physical examination. Medscape. Updated September 21, 2022. Accessed December 16, 2022.
Passamonti F, Rumi E, Arcaini L, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica. 2008;93(11):1645-1651. doi:10.3324/haematol.13346
Platelet disorders: thrombocythemia and thrombocytosis. National Heart, Lung, and Blood Institute. Updated March 24, 2022. Accessed December 16, 2022.
Coltro G, Mannelli F, Loscocco GG, et al. Differential prognostic impact of cytopenic phenotype in prefibrotic vs overt primary myelofibrosis. Blood Cancer J. 2022;12(8):116. doi:10.1038/s41408-022-00713-6
Boiocchi L, Gianelli U, Iurlo A, et al. Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications. Mod Pathol. 2015;28(11):1448-1457. doi:10.1038/modpathol.2015.100
High white blood cell count. Cleveland Clinic. Assessed December 16, 2022.
Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021;96(1):145-162. doi:10.1002/ajh.26050
Leukoerythroblastic peripheral blood smear. UpToDate. Accessed December 16, 2022.
Constitutional symptom. National Library of Medicine. Accessed December 16, 2022.
Constitutional symptoms. Health Jade. Accessed December 16, 2022.
Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33(9):1199-1203. doi:10.1016/j.leukres.2009.01.035
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

Reviewed by Kyle Habet, MD, on 12/20/2022.

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.

Myelofibrosis (MF)