Myelofibrosis and Central Retinal Artery Occlusion

Myelofibrosis and 

Central Retinal Artery Occlusion

As far as I can find on Pubmed and Johns Hopkins list of all papers published, there are no case reports of Myelofibrosis causing Central Retinal Artery Occlusion (CRA). There are cases, though of Polycythemia Vera (PCV) causing CRAO. Likely cases of Myelofibrosis with CRAO have the same underlying issue as those with PCV

Here is what I found so far:


 2016 Oct 20;2016. pii: bcr2016216417. doi: 10.1136/bcr-2016-216417.

Central retinal artery occlusion as a presenting manifestation of polycythaemia vera.


A 60-year-old woman with no premorbidities presented with symptoms of sudden painless vision loss in the left eye (LE). Best-corrected visual acuity in the LE was counting fingers close to face. A relative afferent pupillary defect was observed in the LE. Ocular fundus examination of LE was suggestive of central retinal artery occlusion. Systemic evaluation revealed splenomegaly and normal cardiac and carotid arteries. Haematological investigations revealed increased haemoglobin, haematocrit, platelet count and leucocytosis with low erythrocyte sedimentation rate (ESR). Features of myeloproliferative neoplasm were noted on bone marrow aspiration. An assay for JAK2 mutation was positive. Since erythropoietin levels were normal, a diagnosis of primary polycythaemia vera was made and treated with aspirin and phlebotomy twice weekly until the target haematocrit of under 45% was achieved.

2. 2015 Spring;9(2):127-30. doi: 10.1097/ICB.0000000000000114.

Jak2 mutation-positive polycythemia vera presenting as central retinal artery occlusion.

Author information

Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York.



To report the case of a 49-year-old man who presented with profound visual loss in his right eye because of a central retinal artery occlusion, accompanied by a stroke in the ipsilateral middle cerebral artery with left upper extremity sequelae.


The patient underwent a comprehensive ophthalmologic examination, fluorescein angiography, thorough neuroophthalmology evaluation, including magnetic resonance imaging and magnetic resonance angiography, 12-lead electrocardiogram, transesophageal echocardiogram, bilateral carotid artery Doppler, Holter monitoring, comprehensive laboratory testing, bone marrow biopsy, and genetic testing.


Despite an initially normal hematocrit, the etiology of the central retinal artery occlusion and that of the nearly concomitant stroke in the right medial cerebral artery territory was confirmed by bone marrow biopsy to be polycythemia vera (positive JAK2 mutation). Patient received treatment with aspirin, serial phlebotomies, and hydroxyurea, demonstrating a slight improvement in vision and substantial normalization of neurologic and hematological status. At the time of this report, 2 years later, patient remains stable.


Central retinal artery occlusion, a disease with a frequently devastating visual outcome, is often not an “isolated” ocular occurrence. In the absence of an obvious local trigger, a thorough work-up is always warranted, especially in younger patients, as the ocular pathology oftentimes may herald severe cerebro-cardiovascular events.

What Is Primary Myelofibrosis (MF)?

Primary myelofibrosis (MF) is a chronic blood cancer in which excessive scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells.
Researchers believe MF may be caused by abnormal blood stem cells in the bone marrow. The abnormal stem cells produce mature cells that grow quickly and take over the bone marrow, causing both fibrosis (scar tissue formation) and chronic inflammation. As a result, it becomes more difficult for the bone marrow to create normal blood cells and blood cell production may move to the spleen (causing enlargement) or to other areas of the body.
Classified as a myeloproliferative neoplasm (MPN), MF can arise on its own or as a progression of polycythemia vera (post-PV-MF) or essential thrombocythemia (post-ET-MF). The manifestations of MF, post-PV-MF and post-ET-MF are virtually identical and treatment is generally the same for all three.
No one knows exactly what triggers the start of myelofibrosis or other myeloproliferative neoplasms. In the majority of cases, myelofibrosis is not inherited genetically — you cannot pass the disease on to your children or inherit it from your parents (although some families do demonstrate a clear predisposition).
Recently, researchers have discovered that these diseases may be caused by acquired gene mutations (changes in DNA that not inherited). Some of these mutations affect proteins that work in signaling pathways in your cells.

Risk factors associated with MF include:

Myelofibrosis is most often diagnosed in people over the age of 60, although there are known cases of myelofibrosis in the young.
JAK2 Mutation
Approximately 50% to 60% of people with MF have a mutation of the JAK2 gene within their blood-forming cells. Mutant JAK2 tells blood cells to grow and divide even when the body is not asking for more blood cells. Between 5 and 10% of patients will have a mutation in another gene named MPL, which also affects the JAK signaling pathway.
About 23.5% of people with myelofibrosis and essential thrombocythemia have a mutation called Calreticulin, or CALR. This genetic marker was discovered in 2013 by two independent laboratories, including one funded by the MPN Research Foundation. Research is still ongoing, but there are potential implications for treatments and prognosis for those with the CALR mutation.
Physicians review a wide range of factors before making a diagnosis of myelofibrosis. Since every case of MF is different, a medical history, a physical examination, laboratory tests and a bone marrow examination are usually required to diagnose the disease.
Even though some people living with myelofibrosis may not have symptoms (things you feel), they frequently exhibit signs (things a doctor notices during a physical examination).
Common signs of MF during physical examinations may include:
  • An enlarged spleen (splenomegaly) 
  • Pale mucous membranes (pallor), if anemia is present
  • Loss of muscle mass
  • Cachexia (wasting syndrome characterized by weight loss, muscle atrophy, weakness and fatigue)

Common lab tests to diagnose MF include:

Blood Tests
A complete blood count (CBC) often shows abnormal blood cell counts. Red blood cells (erythrocytes), white blood cells (leukocytes), platelets (thrombocytes) or other blood cell types are commonly affected by MF, and counts may be either too high or too low. 
Bone Marrow Biopsy
An examination of bone marrow under a microscope may reveal that suggest MF, including scar tissue formation and the atypical appearance of bone marrow precursors. 
Gene Mutation Analysis of Blood Cells
Specific mutations associated with some cases of MF (e.g., JAK2, CALR, and MPL) can be identified through gene mutation analysis.
Imaging Tests
An ultrasound of the spleen or other tests may be done to determine whether the spleen is enlarged.
Myelofibrosis symptoms are often caused by an enlarged spleen and/or insufficient numbers of normal blood cells and chronic inflammation.
Common MF symptoms and signs may include: 
  • Tiredness, weakness, or shortness of breath with mild exertion
  • Fullness, discomfort or pain in the left upper area of the abdomen
  • Fever
  • Night sweats
  • Weight loss or malnutrition
  • Bone pain 
  • Itching (pruritus)
  • Easy bleeding or bruising
  • Susceptibility to infection
  • Joint pain or gout 
  • Abdominal distension/fluid retention (if portal hypertension or increased blood pressure within the portal vein is present)
  • Compromised liver function
  • Abnormal growth of blood forming cells outside of the bone marrow
Routine medical examinations including complete blood counts (CBCs) are important for diagnosing MF and other MPNs, since some MF patients exhibit no symptoms (especially during the early course of the disease).
There is no single prognosis for people who suffer from myelofibrosis– the prognosis of MF is different for every patient. While some individuals live for many years without developing major symptoms, others find that the disease progresses more quickly. 
Factors that can influence an MF prognosis are age, white blood cell counts, number of “blasts” (immature blood cells) in the blood, “constitutional symptoms” (e.g., night sweats, weight loss, fever), anemia (low red blood cells), transfusion dependence, low platelets and abnormal chromosome analysis. 
For most patients, an MF prognosis requires the management of several symptoms and signs, including:
  • Anemia (not enough red blood cells to carry oxygen)
  • Splenomegaly (enlarged spleen)
  • Extramedullary hematopoiesis (production of blood cells in organs outside the bone marrow, such as the spleen and liver)
  • Thrombosis and thrombohemorrhagic complications (blood clotting or bleeding complications)
  • Leukocytosis (too many white blood cells)
  • Thrombocytosis (too many platelets) or thrombocytopenia (low platelet counts)
  • Constitutional and systemic (“whole body”) symptoms (e.g., fatigue, night sweats, weight loss, pruritus, fever, bone and joint pain)
  • Gout
For a small number of patients, MF can transform to acute myeloid leukemia (AML), a serious blood and bone marrow cancer. When AML does arise from MF, it progresses quickly and can be difficult to treat.
There is no single treatment that is effective for all MF sufferers. Each patient has a unique set of symptoms and circumstances that require different treatment options, as prescribed by a doctor. Also, some patients with MF remain symptom-free for many years and may not require immediate treatment. However, anyone who has been diagnosed with MF needs to be monitored over time for signs or symptoms that suggest the disease has worsened.

Available treatments and therapies for MF include:

Jakafi (ruloxitinib) is the first drug approved by the FDA for treating MF patients. Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MFAs a targeted therapy, Jakafi is designed to be more specific for abnormal cells. Taken orally, Jakafi partially inhibits the activity of JAK2 and the related protein JAK1. During clinical trials, it was shown to reduce spleen size, abdominal discomfort, early satiety, bone pain, night sweats and itching in MF patients as well as the level of “pro-inflammatory cytokines” in the blood, which may cause some symptoms such as fatigue, fever, night sweats and weight loss. Patients are observed for low blood counts, headache, dizziness, bruising or infection. For more about Jakafi, click here (will be directed to the manufacturer’s website).
Allogenic Stem Cell Transplantation (ASCT) 
ASCT is the only curative treatment for MF. Patients need to carefully discuss whether or not they may be eligible for such a procedure, given the complexity and possibility for complications. With ASCT, hematopoietic (blood-forming) stem cells are transferred from a donor to the patient, essentially replacing defective stem cells with healthy ones. Before the stem cell infusion, the patient receives chemotherapy and/or radiation therapy to eradicate diseased bone marrow. Since age and the presence of other diseases elevate the risks associated with ASCT, the decision to pursue ASCT should be made in close consultation with your physician.

Symptom-Specific Treatments 

In many cases, therapies for MF patients target specific signs. These signs and related treatments can include:
  • Anemia may be treated with corticosteroids, androgens (including danazol and halotestin), thalidomide, lenalidomide, blood   transfusions, or erythropoiesis stimulating agents (ESAs). There are also some drugs currently in clinical trial that aim to improve anemia for people with myelofibrosis.
  • Splenomegaly may be treated with Jakafi, hydroxyurea (HU), cladibrine, interferon, or, in severe cases when drug therapy has failed, radiation or splenectomy. 
  • Risk of thrombosis may be managed with low-dose aspirin therapy or hydroxyurea. 
  • Non-liver and spleen extramedullary hematopoiesis may be treated with radiation therapy. 
  • Constitutional symptoms, such as night sweats, pruritus, weight loss and fever may be treated with Jakafi. 

Novel Approaches and Clinical Trials 

For many patients with MF, available treatment approaches may not be effective, and experimental treatments (which involve receiving a novel drug or treatment on a clinical trial), may be an appropriate option.
So far, only Jakafi (ruxolitinib) has been FDA approved for MF therapy. But other novel therapies are currently in clinical trial, including multiple mechanisms of action:
JAK Inhibitors
A number of other drugs that inhibit JAK2 (“JAK inhibitors”) are currently in clinical trials, including momelotinib, pacrtinib and NS-018. The results of these studies will determine whether these drugs may also be effective for treating MF patients. 
Epigenetic Drugs
Epigenetic drugs change the way genes are organized to make them more or less accessible for use by the cell. Recent studies with epigenetic drugs have found that the HDAC inhibitor, Givinostat, and two hypomethylating agents, azacitidine and decitabine, were minimally effective in treating MF in early studies (in contrast to their effectiveness in treating PV). Another HDAC inhibitor, panobinostat, is under study.
Pomalidomide has been shown to effectively treat anemia in early studies. It targets the patient’s immune system to attack abnormal cells in order to make room for the normal cells that make red blood cells. With enhanced anti-cancer activity and lower toxicity compared to the other drugs in its class, pomalidomide has shown promise in initial studies and is now in phase 3 clinical trials for its use as first line therapeutic for treating anemia in MF patients who have the V617F mutation.
Everolimus (also known as RAD001) is an inhibitor of the mTOR/AKT pathway, which is highly active in MF blood producing cells and appears to contribute to abnormal cell growth. In phase 1 and 2 clinical trials, Everolimus was well tolerated and able to reduce both spleen size and systemic symptoms. 

Ready to Change Your Prognosis?

At the MPN Research Foundation, we’re dedicated to providing advocacy, education and support services for MF patients and their families. Sign up to receive the latest news and updates about myelofibrosis treatments and other topics, and let’s change your MF prognosis together.

 1997 Nov;68(11):734-8.

Retinopathy secondary to anemia from myeloid metaplasia in polycythemia vera.



Polycythemia vera is a chronic clonal disorder associated with excessive proliferation of erythrocytes, leukocytes, and thrombocytes, as well as an accompanying splenomegaly. Ocular manifestations of polycythemia vera include occipital cortex transient ischemic attacks, transient monocular blindness, vaso-occlusive disease, and retinal hemorrhages.


A 56-year old man with longstanding polycythemia vera sought treatment for a chief symptom of blurred vision in the left eye and a red tinge to things first noticed on awakening that morning. He had preretinal and intraretinal hemorrhages and was subsequently found to be severely anemic as a result of postpolycythemic myeloid metaplasia after years of phlebotomy. Splenectomy controlled his anemia and thrombocytopenia, allowing transient improvement of the retinal hemorrhages. Acute leukemia subsequently developed and the patient died 7 weeks after initial examination.


In this case, preretinal and intraretinal hemorrhages were found in a patient with longstanding polycythemia vera. The exact origin of these hemorrhages is uncertain. They are probably secondary to anemia, but the possibility that they are sites of extramedullary hematopoiesis must be considered. The appearance of retinal hemorrhages warrants careful investigation to rule out diabetes, hypertension, and anemia, as well as the various other blood dyscrasias.

Here is the whole list of Search Words: Polycythemia Vera:

Search results

Items: 23

Rostron E, Dickerson MP, Heath G.
BMJ Case Rep. 2017 Jan 30;2017. pii: bcr2016214955. doi: 10.1136/bcr-2016-214955.


Rao K, Shenoy SB, Kamath Y, Kapoor S.
BMJ Case Rep. 2016 Oct 20;2016. pii: bcr2016216417. doi: 10.1136/bcr-2016-216417.


Marton I, Simon Z, Borbényi Z.
Orv Hetil. 2016 Oct;157(44):1743-1751. Hungarian.


Dhrami-Gavazi E, Lee W, Horowitz JD, Odel J, Mukkamala SK, Blumberg DM, Weiss M, Winn BJ.
Retin Cases Brief Rep. 2015 Spring;9(2):127-30. doi: 10.1097/ICB.0000000000000114.


Michiels JJ, Berneman Z, Gadisseur A, Lam KH, De Raeve H, Schroyens W.
Acta Haematol. 2015;133(1):56-63. doi: 10.1159/000360388.


Rue KS, Hirsch LK, Sadun AA.
Clin Ophthalmol. 2012;6:1763-5. doi: 10.2147/OPTH.S33456.




Free PMC Article

Zhang H, Yang Y, Cui J, Zhang Y.
Indian J Dermatol Venereol Leprol. 2012 Sep-Oct;78(5):532-44. doi: 10.4103/0378-6323.100516. Review.




Free Article

Wautier MP, Héron E, Picot J, Colin Y, Hermine O, Wautier JL.
J Thromb Haemost. 2011 May;9(5):1049-55. doi: 10.1111/j.1538-7836.2011.04251.x.




Free Article

Mahendradas P, Shetty R, Avadhani K, Ross C, Gupta A, Shetty BK.
Ocul Immunol Inflamm. 2010 Aug;18(4):319-21. doi: 10.3109/09273941003798767.


Nithyanandam S.
Indian J Ophthalmol. 2009 Jul-Aug;57(4):325. doi: 10.4103/0301-4738.53067. No abstract available.




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Parija S, Mohapatra MM, Pattnaik BK.
Indian J Ophthalmol. 2008 Jul-Aug;56(4):327-9.




Free PMC Article

Tönz MS, Rigamonti V, Iliev ME.
Klin Monbl Augenheilkd. 2008 May;225(5):504-6. doi: 10.1055/s-2008-1027304.


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J Neurol Sci. 2007 Jul 15;258(1-2):151-3.


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J Mal Vasc. 2005 Feb;30(1):46-52. Review. French.


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AANA J. 2004 Aug;72(4):285-92. Review.


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Acta Neurol Scand. 2000 Nov;102(5):299-302.


Blood AM, Lowenthal EA, Nowakowski RW.
J Am Optom Assoc. 1997 Nov;68(11):734-8.


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Schweiz Rundsch Med Prax. 1986 May 27;75(22):671-4. German. No abstract available.


Pouillot B, Pecker J, Guegan Y, Estable A, Baudet D.
Neurochirurgie. 1984;30(2):131-4. French.


Jabaily J, Iland HJ, Laszlo J, Massey EW, Faguet GB, Brière J, Landaw SA, Pisciotta AV.
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From Wikipedia, the free encyclopedia
Classification and external resources
Specialty Oncology and Hematology
ICD10 C94.4D47.4
ICD9-CM 289.83
ICD-O 9931/3, M9961/3
OMIM 254450
DiseasesDB 8616
MedlinePlus 000531
Patient UK Myelofibrosis
MeSH D055728
Myelofibrosis, also known as osteomyelofibrosis, is a relatively rare bone marrow cancer.[1] It is currently classified as a myeloproliferative neoplasm, in which the proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue.[2][3]
The term myelofibrosis alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (cIMF); the terms idiopathic and primary mean that in these cases the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to polycythemia vera or essential thrombocythaemia. Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone marrow, and often the two terms are used synonymously. The terms agnogenic myeloid metaplasia and myelofibrosis with myeloid metaplasia (MMM) are also used to refer to primary myelofibrosis.

Signs and symptoms[edit]

The primary sign of myelofibrosis is reactive bone marrow fibrosis,[3] but it is often accompanied by:


There is an association between mutations to the JAK2CALR, or MPL gene and myelofibrosis.[5] Approximately 90% of those with myelofibrosis have one of these mutations and 10% carry none of these mutations. These mutations are not specific to myelofibrosis, and are linked to other myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia.[3]
The V617F mutation to the JAK2 protein is found in approximately half of individuals with primary myelofibrosis.[6] The V617F mutation is a change of valine to phenylalanine at the 617 position. Janus kinases (JAKs) are non-receptor tyrosine kinases essential for the activation of signaling that is mediated by cytokine receptors lacking catalytic activity. These include receptors for erythropoietinthrombopoietin, most interleukins and interferon.[6] JAK2 mutations are significant because JAK2 plays a role in controlling production of blood cells from hematopoietic stem cells. The V617F mutation appears to make hematopoietic cells more sensitive to growth factors that need JAK2 for signal transduction, which include erythropoietin and thrombopoietin.[7]
The MPL gene codes for a protein that acts as a receptor for thrombopoietin. A mutation in that gene, known as a W515 mutation, leads to the production of an abnormal thrombopoietin receptor protein, which results in the overproduction of abnormal megakaryocytes. The abnormal megakaryocytes stimulate other cells, the fibroblasts, to produce collagen in the bone marrow.[8]


Myelofibrosis is a clonal neoplastic disorder of hematopoiesis, the formation of blood cellular components. It is one of the myeloproliferative disorders, diseases of the bone marrow in which excess cells are produced at some stage. Production of cytokines such as fibroblast growth factor by the abnormal hematopoietic cell clone (particularly by megakaryocytes)[9] leads to replacement of the hematopoietic tissue of the bone marrow by connective tissue via collagen fibrosis. The decrease in hematopoietic tissue impairs the patient’s ability to generate new blood cells, resulting in progressive pancytopenia, a shortage of all blood cell types. However, the proliferation of fibroblasts and deposition of collagen is a secondary phenomenon, and the fibroblasts themselves are not part of the abnormal cell clone.
In primary myelofibrosis, progressive scarring, or fibrosis, of the bone marrow occurs, for the reasons outlined above. The result is extramedullary hematopoiesis, ie. blood cell formation occurring in sites other than the bone marrow, as the haemopoetic cells are forced to migrate to other areas, particularly the liver and spleen. This causes an enlargement of these organs. In the liver, the abnormal size is called hepatomegaly. Enlargement of the spleen is called splenomegaly, which also contributes to causing pancytopenia, particularly thrombocytopenia and anemia. Another complication of extramedullary hematopoiesis is poikilocytosis, or the presence of abnormally shaped red blood cells.
Myelofibrosis can be a late complication of other myeloproliferative disorders, such as polycythemia vera, and less commonly, essential thrombocythaemia. In these cases, myelofibrosis occurs as a result of somatic evolution of the abnormal hematopoietic stem cell clone that caused the original disorder. In some cases, the development of myelofibrosis following these disorders may be accelerated by the oral chemotherapy drug hydroxyurea.[10]
The cause and risk factors for primary myelofibrosis are unknown.

Sites of hematopoiesis[edit]

The principal site of extramedullary hematopoiesis in myelofibrosis is the spleen, which is usually markedly enlarged, sometimes weighing as much as 4000 g. As a result of massive enlargement of the spleen, multiple subcapsular infarcts often occur in the spleen, meaning that due to interrupted oxygen supply to the spleen partial or complete tissue death happens. On the cellular level, the spleen contains red blood cell precursors, granulocyte precursors and megakaryocytes, with the megakaryocytes prominent in their number and in their bizarre shapes. Megakaryocytes are believed to be involved in causing the secondary fibrosis seen in this condition, as discussed under “Pathophysiology” above. Sometimes unusual activity of the red blood cellswhite blood cells, or platelets is seen.
The liver is often moderately enlarged, with foci of extramedullary hematopoiesis. Microscopically, lymph nodes also contain foci of hematopoiesis, but these are insufficient to cause enlargement.
There are also reports of hematopoiesis taking place in the lungs. These cases are associated with hypertension in the pulmonary arteries.[11]
The bone marrow in a typical case is hypercellular and diffusely fibrotic. Both early and late in disease, megakaryocytes are often prominent and are usually dysplastic.


Epidemiologically, the disorder usually develops slowly and is mainly observed in people over the age of 50.[12] It may also develop as a side-effect of treatment with some drugs that target hematological disorders, such as polycythemia vera or chronic myelogenous leukemia. Diagnosis of myelofibrosis is made on the basis of bone marrow biopsy.[3] A physical exam of the abdomen may reveal enlargement of the spleen, the liveror both.[3]
Blood tests are also used in diagnosis. Primary myelofibrosis can begin with a blood picture similar to that found in polycythemia vera or chronic myelogenous leukemia. Most people with myelofibrosis have moderate to severe anemia. Eventually thrombocytopenia, a decrease of blood platelets develops. When viewed through a microscope, a blood smear will appear markedly abnormal, with presentation of pancytopenia, which is a reduction in the number of all blood cell types: red blood cellswhite blood cells, and platelets. Red blood cells may show abnormalities including bizarre shapes, such as teardrop-shaped cells, and nucleated red blood cell precursors may appear in the blood smear. (Normally, mature red blood cells in adults do not have a cell nucleus, and the presence of nucleated red blood cells suggests that immature cells are being released into the bloodstream in response to a very high demand for the bone marrow to produce new red blood cells.) Immature white cells are also seen in blood samples, and basophil counts are increased.
When late in the disease progression an attempt is made to take a sample of bone marrow by aspiration, it may result in a dry tap, meaning that where the needle can normally suck out a sample of semi-liquid bone marrow, it produces no sample because the marrow has been replaced with collagen fibers. A bone marrow biopsy will reveal collagen fibrosis, replacing the marrow that would normally occupy the space.


The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks.[13] Other treatment options are largely supportive, and do not alter the course of the disorder (with the possible exception of ruxolitinib, as discussed below).[14] These options may include regular folic acid,[15] allopurinol[16] or blood transfusions.[17] Dexamethasone, alpha-interferon and hydroxyurea (also known as hydroxycarbamide) may play a role.[18][19][20]
Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.[20]
Frequent blood transfusions may also be required.[17] If the patient is diabetic and is taking a sulfonylurea, this should be stopped periodically to rule out drug-induced thrombocytopenia.[citation needed]
Splenectomy is sometimes considered as a treatment option for patients with myelofibrosis in whom massive splenomegaly is contributing to anaemia because of hypersplenism, particularly if they have a heavy requirement for blood transfusions. However, splenectomy in the presence of massive splenomegaly is a high-risk procedure, with a mortality risk as high as 3% in some studies.[21]
In November 2011, the FDA approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis.[22][23] Ruxolitinib serves as an inhibitor of JAK 1 and 2. The New England Journal of Medicine (NEJM) published results from two Phase III studies of ruxolitinib. These data showed that the treatment significantly reduced spleen volume, improved symptoms of myelofibrosis, and was associated with improved overall survival compared to placebo.[24][25]


Myelofibrosis was first described in 1879 by Gustav Heuck.[26][27]
Older terms include “myelofibrosis with myeloid metaplasia” and “agnogenic myeloid metaplasia”. The World Health Organization utilized the name “chronic idiopathic myelofibrosis”, while the International Working Group on Myelofibrosis Research and Treatment calls the disease “primary myelofibrosis”. In 2008 WHO has adopted the name of “primary myelofibrosis.” Eponyms for the disease are Heuck-Assmann disease or Assmann’s Disease, for Herbert Assmann,[28] who published a description under the term “osteosclerosis” in 1907.[29]
It was characterised as a myeloproliferative condition in 1951 by Dameshek.[30][31] The Leukemia and Lymphoma Society describes myelofibrosis as a rare type of blood cancer, manifesting as a type of chronic leukemia.[32]


  1. Jump up^ “Myelofibrosis Facts” (PDF)The Leukemia and Lymphoma Society. Retrieved 5 October 2014.
  2. Jump up^ myelofibrosis” at Dorland’s Medical Dictionary
  3. Jump up to:a b c d e Tefferi, Ayalew (2014). “Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management”. American Journal of Hematology89 (9): 915–925. doi:10.1002/ajh.23703ISSN 0361-8609.
  4. Jump up^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews’ Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
  5. Jump up^ Tefferi, A; Lasho, T L; Finke, C M; Knudson, R A; Ketterling, R; Hanson, C H; Maffioli, M; Caramazza, D; Passamonti, F; Pardanani, A (2014). “CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons”. Leukemia28 (7): 1472–1477. doi:10.1038/leu.2014.3ISSN 0887-6924.
  6. Jump up to:a b Staerk, Judith; Constantinescu, Stefan N. (2014). “The JAK-STAT pathway and hematopoietic stem cells from the JAK2 V617F perspective”. JAK-STAT1 (3): 184–190. doi:10.4161/jkst.22071ISSN 2162-3996.
  7. Jump up^ Them, Nicole C. C.; Kralovics, Robert (2013). “Genetic Basis of MPN: Beyond JAK2-V617F”. Current Hematologic Malignancy Reports8 (4): 299–306. doi:10.1007/s11899-013-0184-zISSN 1558-8211.
  8. Jump up^ Tefferi, A (2010). “Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1”. Leukemia24 (6): 1128–1138. doi:10.1038/leu.2010.69ISSN 0887-6924.
  9. Jump up^ Chou JM, et al. (2003). “Bone marrow immunohistochemical studies of angiogenic cytokines and their receptors in myelofibrosis with myeloid metaplasia”. Leukemia Research27 (6): 499–504. doi:10.1016/S0145-2126(02)00268-0PMID 12648509.
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  22. Jump up^ “FDA Approves Incyte’s Jakafi(TM) (ruxolitinib) for Patients with Myelofibrosis” (Press release). Incyte. Retrieved 2012-01-02.
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  26. Jump up^ Lichtman MA (July 2005). “Is it chronic idiopathic myelofibrosis, myelofibrosis with myeloid metaplasia, chronic megakaryocytic-granulocytic myelosis, or chronic megakaryocytic leukemia? Further thoughts on the nosology of the clonal myeloid disorders”. Leukemia19 (7): 1139–41. doi:10.1038/sj.leu.2403804PMID 15902283.
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  28. Jump up^ synd/2799 at Who Named It?,
  29. Jump up^ Ansell, Stephen M. (1 January 2008). Rare Hematological Malignancies. Springer Science+Business Media, LLC. pp. 28–. ISBN 978-0-387-73744-7.
  30. Jump up^ Judith E. Karp (2007). Acute myelogenous leukemia. Humana Press. pp. 385–. ISBN 978-1-58829-621-4. Retrieved 13 November 2010.
  31. Jump up^ Dameshek W (April 1951). “Some speculations on the myeloproliferative syndromes”Blood6 (4): 372–5. PMID 14820991.
  32. Jump up^ “Myelofibrosis Facts” (PDF). Leukemia and Lymphoma Society. Retrieved 20 December 2012.
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