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

- Fatigue

- 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.

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.

Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:

In 2008, the World Health Organization listed these diagnoses as types of MPD:

- Chronic myelogenous leukemia (BCR-ABL1–positive)

- Chronic neutrophilic leukemia

- Polycythemia vera

- Primary myelofibrosis

- Essential thrombocythemia

- Chronic eosinophilic leukemia (not otherwise specified)

- Mastocytosis

The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek. In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.

The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.

Most people with ET are without symptoms referable to ET at the time of diagnosis, which is usually ultimately made after noting an elevated platelet level on a routine complete blood count (CBC). The most common symptoms are bleeding (due to dysfunctional platelets), blood clots (e.g., deep vein thrombosis or pulmonary embolism), headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities; the most common signs are increased white blood cell count, reduced red blood cell count, and an enlarged spleen.

Polycythemia vera is an uncommon neoplasm in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets.

Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the increased red blood cells. It is more common in the elderly and may be symptomatic or asymptomatic. Common signs and symptoms include itching (pruritus), and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish coloration of the skin. Patients with polycythemia vera are more likely to have gouty arthritis. Treatment consists primarily of phlebotomy.

Myelophthisic anemia (or myelophthisis) is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue either by fibrosis, tumors or granulomas. The word comes from the roots "myelo-", which refers to bone marrow, and "phthysis", shrinkage or atrophy.

People with polycythemia vera can be asymptomatic. A classic symptom of polycythemia vera is pruritus or itching, particularly after exposure to warm water (such as when taking a bath), which may be due to abnormal histamine release or prostaglandin production. Such itching is present in approximately 40% of patients with polycythemia vera. Gouty arthritis may be present in up to 20% of patients. Peptic ulcer disease is also common in patients with polycythemia vera; most likely due to increased histamine from mast cells, but may be related to an increased susceptibility to infection with the ulcer-causing bacterium "H. pylori". Another possible mechanism for the development for peptic ulcer is increased histamine release and gastric hyperacidity related with polycythemia vera.

A classic symptom of polycythemia vera (and the related myeloproliferative disease essential thrombocythemia) is erythromelalgia. This is a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness" (aggregation), resulting in the formation of tiny blood clots in the vessels of the extremity; it responds rapidly to treatment with aspirin.

Patients with polycythemia vera are prone to the development of blood clots (thrombosis). A major thrombotic complication (e.g. heart attack, stroke, deep venous thrombosis, or Budd-Chiari syndrome) may sometimes be the first symptom or indication that a person has polycythemia vera.

Headaches, lack of concentration and fatigue are common symptoms that occur in patients with polycythemia vera as well.

Bone marrow biopsy shows abnormal megakaryocytes, macrocytic erythropoiesis, and defects in neutrophil production and fibrosis of the marrow (myelofibrosis).

Clinically patients present with reduction in the count of all blood cells (pancytopenia), a very few blasts in the peripheral blood and no or little spleen enlargement (splenomegaly).

Cells are usually CD34 positive.

Myelophthisis can occur in the setting of chronic myeloproliferative disease (e.g. myelofibrosis), leukemia, lymphoma, and metastatic carcinoma or myeloma. It is common in people who have chronic idiopathic myelofibrosis. It has been linked to small-cell lung cancer, breast cancer or prostate cancer that metastasizes to the bone marrow.

Historically, the most common cause of displacement of healthy bone marrow was tuberculosis.

Currently, the most common cause is displacement of bone marrow by metastatic cancer (extramedullary hematopoiesis tends to be modest). Other causes include myeloproliferative disorders (especially late-stage or spent polycythemia vera), granulomatous diseases, and (lipid) storage diseases. Myelofibrosis can occur in all of these.

Factors that may contribute to decreased RBC production include a decreased quantity of functioning hematopoietic tissue, disordered metabolism related to the underlying disorder, and, in some cases, erythrophagocytosis.

Essential thrombocythemia (ET) is a rare chronic blood condition characterised by the overproduction of platelets by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid leukemia or myelofibrosis. It is one of four myeloproliferative neoplasms (blood cancers that occur when the body makes too many white or red blood cells, or platelets).

Acute panmyelosis with myelofibrosis (APMF) it is a poorly defined disorder that arises as either a clonal disorder, or following toxic exposure to the bone marrow.

Very rarely, chloroma can occur without a known pre-existing or concomitant diagnosis of acute leukemia, acute promyleocytic leukemia or MDS/MPS; this is known as primary chloroma. Diagnosis is particularly challenging in this situation (see below). In almost all reported cases of primary chloroma, acute leukemia has developed shortly afterward (median time to development of acute leukemia 7 months, range 1–25 months). Therefore, primary chloroma could be considered an initial manifestation of acute leukemia, rather than a localized process, and could be treated as such. Where disease development or markers indicate progresses to acute promyleocytic leukemia (AML3) treatment should be tailored to this form of disease.

Chloromas may occur in virtually any organ or tissue. The most common areas of involvement are the skin (also known as "leukemia cutis") and the gums. Skin involvement typically appears as violaceous, raised, nontender plaques or nodules, which on biopsy are found to be infiltrated with myeloblasts

Other tissues which can be involved include lymph nodes, the small intestine, the mediastinum, the lung, epidural sites, the uterus, the ovaries, and the orbit of the eye. Symptoms of chloroma at these sites are related to their anatomic location; chloromas may also be asymptomatic and be discovered incidentally in the course of evaluation of a person with acute myeloid leukemia.

Central nervous system involvement, as described above, most often takes the form of "meningeal leukemia", or invasion of the subarachnoid space by leukemic cells. This condition is usually considered separately from chloroma, as it requires different treatment modalities. True chloromas (i.e. solid leukemic tumors) of the central nervous system are exceedingly rare, but has been described.

In hairy cell leukemia, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets. Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count. Leukemic cells may gather in the spleen and cause it to swell; this can have the side effect of making the person feel full even when he or she has not eaten much.

Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers of one or more kinds of normal blood cells, or after unexplained bruises or recurrent infections in an otherwise apparently healthy patient.

Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect. It may result in somewhat more mild bruises than would otherwise be expected for a given platelet count or a mildly increased bleeding time for a minor cut. It is likely the result of producing slightly abnormal platelets in the overstressed bone marrow tissue.

Patients with a high tumor burden may also have somewhat reduced levels of cholesterol, especially in patients with an enlarged spleen. Cholesterol levels return to more normal values with successful treatment of HCL.

Acute megakaryoblastic leukemia (AMKL) is a form of leukemia where a majority of the blasts are megakaryoblastic.

It is classified under AML-M7 category of the French-American-British classification.

The latest WHO classification (2008, Lyon), classifies Acute Myeloid Leukemia into distinct subtypes, based on clinico-pathological and molecular features. Acute megakaryoblastic leukemia is placed under the AML-Not Otherwise Specified subcategory.

Diagnosis requires more than 20% Blasts in the marrow/ peripheral blood with more than 50% demonstrating megakaryocytic derivation by morphology, immunophenotypic or electron microscopic studies.

Anemia may lead to malaise, pallor and associated symptoms such as palpitations.

Low platelet counts (thrombocytopenia) if present is associated with an increased risk of hemorrhage, bruising and petechiae. Low white blood cell counts (leukocytopenia) if present leads to an increased risk of infections which can be severe.

Aplastic anemia is a rare disease in which the bone marrow and the hematopoietic stem cells that reside there are damaged. This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). "Aplastic" refers to inability of the stem cells to generate mature blood cells.

It is most prevalent in people in their teens and twenties, but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about half the cases, the cause is unknown.

The definitive diagnosis is by bone marrow biopsy; normal bone marrow has 30–70% blood stem cells, but in aplastic anemia, these cells are mostly gone and replaced by fat.

First line treatment for aplastic anemia consists of immunosuppressive drugs, typically either anti-lymphocyte globulin or anti-thymocyte globulin, combined with corticosteroids and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related matched marrow donor.

Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.

If only two parameters from the full blood count are low, the term bicytopenia can be used. The diagnostic approach is the same as for pancytopenia.

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.

Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope.

The most common causes of splenomegaly in developed countries are infectious mononucleosis, splenic infiltration with cancer cells from a hematological malignancy and portal hypertension (most commonly secondary to liver disease, and sarcoidosis). Splenomegaly may also come from bacterial infections, such as syphilis or an infection of the heart's inner lining (endocarditis).

The possible causes of moderate splenomegaly (spleen <1000 g) are many, and include:

The causes of massive splenomegaly (spleen >1000 g) are fewer, and include:

- visceral leishmaniasis (kala-azar)

- chronic myelogenous leukemia

- myelofibrosis

- malaria

- splenic marginal zone lymphoma

Iatrogenic causes of pancytopenia include chemotherapy for malignancies if the drug or drugs used cause bone marrow suppression. Rarely, drugs (antibiotics, blood pressure medication, heart medication) can cause pancytopenia.

The antibiotics Linezolid and Chloramphenicol can cause pancytopenia in some individuals.

Rarely, pancytopenia may have other causes, such as mononucleosis, or other viral diseases. Increasingly, HIV is itself a cause for pancytopenia.

- Familial hemophagocytic syndrome

- Aplastic anemia

- Gaucher's disease

- metastatic carcinoma of bone

- Multiple Myeloma

- overwhelming infections

- Lymphoma

- myelofibrosis

- Dyskeratosis congenita

- Myelodysplastic syndrome

- Leukemia

- Leishmaniasis

- Severe Folate or vitamin B12 deficiency

- Systemic lupus erythematosus

- Paroxysmal nocturnal hemoglobinuria (blood test)

- Viral infections (such as HIV, EBV--undetermined virus is most common).

- Alimentary toxic aleukia

- Copper deficiency

- Pernicious anemia

- Medication

- Hypersplenism

- Osteopetrosis

- Organic acidurias (Propionic Acidemia, Methylmalonic Aciduria, Isovaleric Aciduria)

- Low dose arsenic poisoning

- Sako disease (Myelodysplastic-cytosis)

- Chronic radiation sickness

- LIG4 syndrome

Complete remission and long-term survival are more common in children than adults.

Prognosis depends upon the cause. One third of cases is associated with a t(1;22)(p13;q13) mutation in children. These cases carry a poor prognosis.

Another third of cases is found in Down syndrome. These cases have a reasonably fair prognosis.

The last third of cases may be heterogeneous, and carry a poor prognosis.

Polycythemia (also known as polycythaemia or polyglobulia) is a disease state in which the hematocrit (the volume percentage of red blood cells in the blood) is elevated.

It can be due to an increase in the number of red blood cells ("absolute polycythemia") or to a decrease in the volume of plasma ("relative polycythemia"). Polycythemia is sometimes called erythrocytosis, but the terms are not synonymous, because polycythemia refers to any increase in red blood cells, whereas erythrocytosis only refers to a documented increase of red cell mass.

The emergency treatment of polycythemia (e.g., in hyperviscosity or thrombosis) is by phlebotomy (removal of blood from the circulation). Depending on the underlying cause, phlebotomy may also be used on a regular basis to reduce the hematocrit. Cytostatics such as busulfan and hydroxyurea are sometimes used for long-term management of polycythemia.

The overproduction of red blood cells may be due to a primary process in the bone marrow (a so-called myeloproliferative syndrome), or it may be a reaction to chronically low oxygen levels or, rarely, a malignancy. Alternatively, additional red blood cells may have been received through another process—for example, being over-transfused (either accidentally or, as blood doping, deliberately) or being the recipient twin in a pregnancy, undergoing twin-to-twin transfusion syndrome.