Myelofibrosis

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Overview

Myelofibrosis with myeloid metaplasia, also known as agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, and primary myelofibrosis, was first described in 1879 and is currently classified as a myeloproliferative disease caused by the growth and proliferation of an abnormal bone marrow stem cell, resulting in the replacement of the bone marrow with fibrous connective tissue. An eponym for the disease is Heuck-Assmann disease, or Assmann's Disease.

Pathophysiology

The bone marrow is replaced by collagen fibrosis, impairing the patient's ability to generate new blood cells resulting in a progressive pancytopenia. It is usually reactive following other myeloproliferative disorders, such as polycythemia rubra vera or essential thrombocytosis. Extramedullary hematopoeisis occurs as the haemopoetic cells migrate away from the bone marrow, to the liver and spleen. Patients often have hepatosplenomegaly and poikilocytosis.

In primary myelofibrosis, a progressive scarring (fibrosis) of the bone marrow occurs. As a result, blood forms in sites other than the bone marrow, such as the liver and spleen. This causes an enlargement of these organs. The cause and risk factors are unknown. It commonly occurs in the spent phase of Polycythemia rubra vera, possibly in response to the medication hydroxyurea poisoning the marrow.

Genetic associations with JAK2 and MPL have been described.

Signs and symptoms

• Abdominal fullness related to an enlarged spleen (splenomegaly).
• Bone pain
• Bruising and easy bleeding due to inadequate numbers of platelets
• Fatigue
• Increased susceptibility to infection, such as pneumonia or diarrhea
• Pallor and shortness of breath while doing physical work due to anemia

Diagnosis

Diagnosis is based upon:

• Normochromic normocytic anaemia
• Red cell poikilocytosis on blood film (tear-drop shaped RBCs)
• JAK 2 mutation on Val 617 Phe locus in 50%
• Raised levels of lactate dehydrogenase
• Raised neutrophil alkaline phosphatase score
• Bone marrow biopsy may show increased cellularity and fibrosis

The patient with the myelofibrosis should be tested for Tuberculosis even if the patient doesn't manifest the symptoms of TB. There is strong evidence of myelofibrois improvement with the antituberculous treatment.

Diagnostic Findings

MRI

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  Myelofibrosis

Treatment

The only known cure is allogeneic stem cell transplantation, but this approach involves significant risks.

Other treatment options are largely supportive, and do not alter the course. These options may include regular folic acid, allopurinol or blood transfusions. Dexamethasone, alpha-interferon and hydroxycarbamide may play a role.

Lenalidomide and Thalidomide may be used in its treatment, though they can cause gout and leave the patient susceptible to diseases such as pneumonia.

Frequent blood transfusions may also be required.

Prognosis

Myelofibrosis leads to progressive bone marrow failure. The mean survival is five years and causes of death include infection, bleeding, organ failure, portal hypertension, and leukemic transformation.

References

Template:Hematology