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:
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.Retin Cases Brief Rep. 2015 Spring;9(2):127-30. doi: 10.1097/ICB.0000000000000114. 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.
Here is what I found so far:
BMJ Case Rep. 2016 Oct 20;2016. pii: bcr2016216417. doi: 10.1136/bcr-2016-216417.
Central retinal artery occlusion as a presenting manifestation of polycythaemia vera.
Jak2 mutation-positive polycythemia vera presenting as central retinal artery occlusion.
What Is Primary Myelofibrosis (MF)?
Risk factors associated with MF include:
Common lab tests to diagnose MF include:
Available treatments and therapies for MF include:
Novel Approaches and Clinical Trials
Ready to Change Your Prognosis?
J Am Optom Assoc. 1997 Nov;68(11):734-8.
Retinopathy secondary to anemia from myeloid metaplasia in polycythemia vera.
Here is the whole list of Search Words: Polycythemia Vera:
From Wikipedia, the free encyclopedia
|Classification and external resources|
|Specialty||Oncology and Hematology|
Myelofibrosis, also known as osteomyelofibrosis, is a relatively rare bone marrow cancer. 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.
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
The primary sign of myelofibrosis is reactive bone marrow fibrosis, but it is often accompanied by:
- Abdominal fullness related to an enlarged spleen (splenomegaly).
- Bone pain
- Bruising and easy bleeding due to inadequate numbers of platelets
- Cachexia (loss of appetite, weight loss, and fatigue)
- Enlargement of both the liver and spleen
- Gout and high uric acid levels
- Increased susceptibility to infection, such as pneumonia
- Pallor and shortness of breath due to anemia
- In rarer cases, a raised red blood cell volume
- Cutaneous myelofibrosis is a rare skin condition characterized by dermal and subcutaneous nodules.:746
There is an association between mutations to the JAK2, CALR, or MPL gene and myelofibrosis. 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.
The V617F mutation to the JAK2 protein is found in approximately half of individuals with primary myelofibrosis. 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 erythropoietin, thrombopoietin, most interleukins and interferon. 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.
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.
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) 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.
The cause and risk factors for primary myelofibrosis are unknown.
Sites of hematopoiesis
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 cells, white 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.
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. 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. A physical exam of the abdomen may reveal enlargement of the spleen, the liver, or both.
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 cells, white 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. Other treatment options are largely supportive, and do not alter the course of the disorder (with the possible exception of ruxolitinib, as discussed below). These options may include regular folic acid, allopurinol or blood transfusions. Dexamethasone, alpha-interferon and hydroxyurea (also known as hydroxycarbamide) may play a role.
Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.
Frequent blood transfusions may also be required. If the patient is diabetic and is taking a sulfonylurea, this should be stopped periodically to rule out drug-induced thrombocytopenia.
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.
In November 2011, the FDA approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis. 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.
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, who published a description under the term “osteosclerosis” in 1907.
It was characterised as a myeloproliferative condition in 1951 by Dameshek. The Leukemia and Lymphoma Society describes myelofibrosis as a rare type of blood cancer, manifesting as a type of chronic leukemia.
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