Myeloproliferative Diseases Flashcards
What are myeloproliferative diseases characterized by?
Clonal proliferation of myeloid haemopoietic cells in the bone marrow
Myeloproliferative diseases are a group of disorders characterized by the overproduction of blood cells.
List the three main types of myeloproliferative diseases.
- Polycythaemia vera (PV)
- Essential thrombocytosis (ET)
- Primary myelofibrosis (MF)
These diseases are closely related and can evolve from one form to another.
What are the key genes involved in myeloproliferative diseases?
- JAK2
- MPL
- CALR
These genes are associated with acquired mutations that lead to these diseases.
What mutation is commonly associated with Polycythaemia vera?
JAK2V617F mutation
This mutation is present in about 97% of patients with Polycythaemia vera.
Define primary polycythaemia.
Increase in haemoglobin concentration above the upper limit of normal for the patient’s age and sex
The red cell mass is greater than 125% of the expected.
What are the cut-off values for diagnosing primary polycythaemia in men and women?
- Hb greater than 185 g/L or haematocrit above 0.52 in men
- Hb greater than 165 g/L or haematocrit above 0.48 in women
These values help distinguish primary polycythaemia from normal variations.
What is the difference between absolute and relative polycythaemia?
- Absolute polycythaemia: increased red cell mass
- Relative polycythaemia: reduced plasma volume
Relative polycythaemia can cause a pseudo rise in packed cell volume.
What are some congenital causes of secondary polycythaemia?
- Defects of the oxygen-sensing pathway
- VHL gene mutation
- PHD2 mutations
- HIF-2α mutations
These genetic defects can lead to increased erythropoietin production.
What are some acquired causes of secondary polycythaemia?
- Tumours (e.g., cerebellar haemangioblastoma, renal cell cancer)
- Drug-associated (e.g., erythropoietin administration)
Acquired causes can significantly influence erythropoietin levels.
Describe the clinical features of Polycythaemia vera.
- Hyperviscosity symptoms
- Plethora
- Splenomegaly
- Thrombosis and bleeding
- Gout and itching
These symptoms arise due to increased red cell mass and associated complications.
What laboratory findings are indicative of Polycythaemia vera?
- JAK2 mutation
- Hct >0.48 in female and >0.52 in male
- Low erythropoietin
- High LDH and uric acid
- Neutrophil leukocytosis
These findings can assist in the diagnosis of the disease.
What is the first-line treatment for Polycythaemia vera?
- Venesection
- Hydroxocarbamide (HU)
- JAK inhibitors (e.g., ruxolitinib)
- Interferon
Treatment aims to reduce symptoms and complications.
What characterizes Essential Thrombocythemia?
Sustained increase in platelet count due to megakaryocyte proliferation
Platelet count is greater than 450,000/cmm.
What are the major diagnostic criteria for Essential Thrombocythemia?
- Pathogenetic mutation (e.g. in JAK2 or CALR)
- No other myeloid malignancy
Diagnosis requires specific criteria to rule out other conditions.
What are common findings in patients with Essential Thrombocythemia?
- Asymptomatic
- Thrombosis
- Bleeding
- Splenomegaly
- Erythromalgia
- Giant platelets
These findings can vary significantly among patients.
What is the treatment for Essential Thrombocythemia?
- Antiplatelets (e.g., aspirin, clopidogrel)
- Hydroxocarbamide
- Anagrelide
- JAK2 inhibitors
Treatment is aimed at managing symptoms and reducing thrombotic risks.
What is primary myelofibrosis?
Development of haemopoiesis in the spleen and liver
It leads to significant clinical symptoms and complications.
What are the clinical features of primary myelofibrosis?
- Anaemia
- Massive splenomegaly
- Hypermetabolic symptoms
- Bleeding
- Bone pain
These features arise from ineffective haemopoiesis and splenic involvement.
What laboratory findings are associated with primary myelofibrosis?
- Leucoerythroblastic features on PBF
- Hypercellular marrow
- High LDH and uric acid
Findings may indicate ineffective haemopoiesis.
What is the median survival for patients with primary myelofibrosis?
About 5 years
Prognosis can vary based on individual circumstances.
