Myeloproliferative Disorders Flashcards
What are myeloproliferative disorders?
Conditions which occur due to uncontrolled proliferation of a single type of stem cell.
What are myeloproliferative disorders considered to be?
A type of bone marrow cancer
What are the three main myeloproliferative disorders?
- Primary myelofibrosis
- Polycythaemia vera
- Essential thrombocythaemia
What is primary myelofibrosis the result of?
The result of proliferation of the hematopoietic stem cells.
What is polycythaemia vera the result of?
The result of proliferation of the erythroid cell line.
What is essential thrombocythemia the result of?
The result of proliferation of the megakaryocytic cell line.
What do Myeloproliferative disorders have the potential to do?
Progress and transform into acute myeloid leukaemia.
What gene mutations are these conditions associated with?
- JAK2
- MPL
- CALR
What gene mutation do the majority of people with polycythaemia vera have?
JAK2 mutation
What is myelofibrosis though to be caused by?
Hyperplasia of abnormal megakaryocytes
What can myelofibrosis be the result of?
- Primary myelofibrosis
- Polycythaemia vera
- Essential thrombocythemia.
What does the proliferation of the cell line lead to in myelofibrosis?
It leads to fibrosis of the bone marrow.
The bone marrow is replaced by scar tissue.
What is fibrosis of the bone marrow the result of?
Cytokines that are released from the proliferating cells.
Especially cytokine- fibroblast growth factor.
What does fibrosis of the bone marrow affect?
The production of blood cells and can lead to anaemia and low white blood cells (leukopenia).
Where does the production of blood cells start to occur when there is fibrosis of the bone marrow?
Liver and Spleen
What is the name of the production of red blood cells in the spleen and liver?
Extramedullary haematopoiesis
What can extramedullary haematopoiesis result in?
hepatomegaly and splenomegaly
How do myeloproliferative disorders present?
- Fatigue (most common presenting symptom)
- Hypermetabolic symptoms: Weight loss, Night sweats, Fever
- Massive splenomegaly
What hypermetabolic symptoms might present with myeloproliferative disorder?
Weight loss
Night sweats
Fever
What might you find on a blood film with primary myeloproliferative disorder?
‘tear-drop’ poikilocytes
What might you find with a FBC?
- anaemia
* high WBC and platelet count early in the disease
What is the management of mild primary myelofibrosis?
Monitored and not actively treated.
What is potentially curative for primary myelofibrosis but carries risk?
Allogenic stem cell transplant
What is the function of chemotherapy in primary myelofibrosis?
Helps to control the disease, improve symptoms and slow progression but is not curative alone
What are 3 key signs of polycythaemia vera?
- Conjunctival plethora (excessive redness to the conjunctiva in the eyes) (red face)
- A “ruddy” complexion
- Splenomegaly
What would you find on a full blood count of someone with polycythaemia vera?
- Raised haemoglobin (more than 185g/l in men or 165g/l in women)
- Primary Thrombocythaemia: Raised platelet count (more than 600 x 109/l)
- Due to proliferation, raised uric acid
What is the first line management of polycythaemia vera?
Venesection
What is the function of venesection?
To keep the haemoglobin in the normal range
What can be used to reduce the risk of developing clots?
Aspirin
What can be used to control the disease of polycythaemia vera?
Chemotherapy
What is the definitive diagnostic test for polycythaemia vera?
Bone marrow biopsy
How does a bone marrow biopsy present with polycythaemia vera?
Dry- all of the aspiration is usually dry
What are the main features of essential thrombocythaemia?
platelet count > 600 * 109/l
both thrombosis (venous or arterial) and haemorrhage can be seen
a characteristic symptom is a burning sensation in the hands
a JAK2 mutation is found in around 50% of patients
What does megakaryocyte proliferation lead to?
Overproduction of platelets
What is the medical management of Essential thrombocythaemia?
Hydroxycarbamide
What is the medical management of essential thrombocythaemia?
Hydroxycarbamide
What is the function of Hydroxycarbamide?
Reduce the platelet count
