MYELOPROLIFERATIVE DISORDERS Flashcards
What are the classic myeloproliferative disorders?
Non cancer:
Polycythaemia vera
Essential thrombocythaemia
Cancer:
Idiopathic myelofibrosis
(CML)
What defines polycythaemia?
Raised PCV (packed cell volume)
What are the upper limits of packed cell volume in men and women?
- 51 in men
0. 48 in women
What are the causes of polycythaemia?
Primary
Polycytheamia vera
Familial (eg Chuvash polycythaemia)
Secondary
Chronic tissue hypoxia (eg COPD)
Ectopic EPO (eg renal disease or extrarenal neoplasms)
Endocrine causes (exogenous EPO and steroids, or endogenous syndromes such as Conn’s and Cushing’s)
What is the term used to describe a rise in packed cell volume without a rise in red cell mass and what is it caused by?
Apparent polycythaemia caused by a reduction in plasma volume
How might someone with suspected polycythaemia vera present?
History of occlusive vascular lesions (eg stroke, TIA, venous thrombosis) Headache Mental clouding Facial redness Itching Abnormal bleeding Gout
What investigations should be ordered for someone with suspected polycythaemia vera?
FBC Red cell mass Serum ferritin Ultrasound to assess size of spleen Investigations into causes of secondary polycythaemia such as EPO levels Bone marrow cytogenic analysis
What would the full blood count of someone with polycythaemia vera show?
Raised WCC
Raised platelet
Raised PCV
Why is it useful to do a serum ferritin in someone with a normal PCV but in whom there are suspicions of polycythaemia?
Iron deficiency may mask raised PCV
How is someone with polycythaemia vera treated?
Repeated venesection to maintain PCV at less than 0.45
Low dose aspirin
Hydroxyurea or interferon-alpha can be used to maintain lower platelet count
How often is venesection performed in someone with polycythaemia vera?
Quite frequently at first but eventually every 6-10 weeks
What is the prognosis for someone diagnosed with polycythaemia vera?
Usually good
20% incidence of transformation to myelofibrosis and 5% to acute leukaemia
How is apparent polycythaemia treated?
Venesection only done in patients with increased risk of vascular complications for other reasons.
What is the central diagnosis feature of essential thrombocythaemia?
A persisting platelet count of more than 600x10^9/L
What are the causes of a rapid increase in platelet count?
Reactive thrombocytosis: Infection Malignancy Inflammatory diseases Haemorrhage Iron deficiency Post-surgery Post-splenectomy Myeloproliferative disorders CML
What is the genetic mutation associated with the myeloproliferative disorders?
JAK2 V617F
What investigations should be performed in someone with suspected essential thrombocythaemia?
JAK2 V617F mutation FBC Blood film ESR CRP Serum ferritin Bone marrow aspirate Trephine (bone marrow) histology
What might be seen in trephine (bone marrow) histology of someone with essential thrombocythaemia?
Clusters of large megakaryocytes
How might someone with essential thrombocythaemia present?
Microvascular occlusive events Burning pain in extremities Digital ischaemia Major vascular occlusive events Stroke MI Bleeding
What can essential thrombocythaemia transform into in a minority of patients?
Myelofibrosis
Acute leukaemia
How are patients with essential thrombocythaemia treated?
Daily low dose of aspirin
Hydroxyurea
Busulfan
Interferon-alpha (particularly useful in pregnancy)
What are the main features of idiopathic myelofibrosis?
Bone marrow fibrosis - replaced with reticulin
Extramedullary haemopoiesis - liver and spleen
Splenomegaly
Leucoerythroblastic picture (immature red and white blood cells)
How do patients with idiopathic myelofibrosis usually present?
Splenomegaly
Anaemia
Fatigue
Bleeding
Constitutional B symptoms may be present
Other than idiopathic myelofibrosis, what might cause a leucoerythroblastic blood film picture?
Bone marrow infiltration Severe sepsis Severe haemolysis Sick neonate Administration of haemopoietic growth factors Acute or chronic leukaemia
What are the two phases of idiopathic myelofibrosis and what might an FBC in each phase show?
Proliferative phase - normal RCC or even raised, raised WCC, raised platelets
Cytopenic phase - reduced FBC
What is the median survival of symptomatic idiopathic myelofibrosis patients?
3 years
What are the treatment options for someone diagnosed with idiopathic myelofibrosis?
Bone marrow transplantation from a match. This cannot be performed in most patients (esp those over 50) due to the toxicity of the procedure
Supportive treatment such as blood transfusions are frequently given
Antifibrotic agents such as thalidomide may be given with varying success
Splenectomy may improve quality of life but not prognosis, by reducing need for transfusions
JAK2 inhibitors
Why might splenectomy be useful in improving quality of life of idiopathic myelofibrosis patients?
Reduce need for transfusions
What is the cause of death in people with idiopathic myelofibrosis?
Haemorrhage
Infection
Transformation to acute leukaemia
Iron overload from blood transfusions
