Myeloproliferative Disorders Flashcards
Myeloproliferative Disorders are
occur due to uncontrolled proliferation of a single type of stem cell. They are considered a type of bone marrow cancer. They include
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia
Primary Myelofibrosis is
the result of proliferation of the hematopoietic stem cells. Polycythaemia vera is the result of proliferation of the erythroid cell line. Essential thrombocythaemia is the result of proliferation of the megakaryocytic cell line
Myeloproliferative disorders have the potential to progress and transform into
primary myeloid leukaemia
These conditions are associated with mutations in certain genes:
JAK2
MPL
CALR
TOM TIP: Remember the JAK2 mutation for your exams. This can be the target of JAK2 inhibitors such as ruxolitinib.
What is Myelofibrosis
Myelofibrosis is where the proliferation of the cell line leads to fibrosis of the bone marrow. The bone marrow is replaced by scar tissue. This is in response to cytokines that are released from the proliferating cells. One particular cytokine is fibroblast growth factor. This fibrosis affects the production of blood cells and can lead to anaemia and low white blood cells (leukopenia).
When the bone marrow is replaced with scar tissue the production of blood cells (haematopoiesis) starts to happen in other areas such as the liver and spleen. This is known as extramedullary haematopoiesis and can lead to hepatomegaly and splenomegaly. This can lead to portal hypertension. If it occurs around the spine it can lead to spinal cord compression.
How does Myelofibrosis present
Initially, myeloproliferative disorders can be asymptomatic.
They can present systemic symptoms:
Fatigue
Weight loss
Night sweats
Fever
There may be signs and symptoms of underlying complications:
Anaemia (except in polycythaemia)
Splenomegaly (abdominal pain)
Portal hypertension (ascites, varices and abdominal pain)
Low platelets (bleeding and petechiae)
Thrombosis is common in polycythaemia and thrombocythaemia
Raised red blood cells (thrombosis and red face)
Low white blood cells (infections)
How does Polycythemia Vera present
Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
A “ruddy” complexion
Splenomegaly
Raised haemoglobin (more than 185g/l in men or 165g/l in women)
How does Primary Thromboycytothaemia present
Raised platelet count (more than 600 x 109/l)
A blood film in myelofibrosis can sow
an show teardrop-shaped RBCs, varying sizes of red blood cells (poikilocytosis) and immature red and white cells (blasts).
How do diagnosis myelofibrosis
Bone marrow biopsy is the test of choice to establish a diagnosis. Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue.
Testing for the JAK2, MPL and CALR genes can help guide management.
Management of Primary Myelofibrosis
Patients with mild disease with minimal symptoms might be monitored and not actively treated.
Allogeneic stem cell transplantation is potentially curative but carries risks.
Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.
Supportive management of the anaemia, splenomegaly and portal hypertension.
Management of polycythaemia vera
Venesection can be used to keep the haemoglobin in the normal range. This is the first line treatment.
Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).
Chemotherapy can be used to control the disease.
Management of Thrombocytopaenia
Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).
Chemotherapy can be used to control the disease.
