MYELOPROLIFERATIVE DISORDERS Flashcards
What are the myeloproliferative disorders?
CML, polycythaemia rubra vera, essential thrombocytopoenia, myelofibrosis
What is the major dysfunction in:Chronic myeloid leukaemia?Polycythaemia rubra vera?Essential thrmbocytopoenia?Myelofibrosis?
Too many myeloid cells + philadelphia chromosome Too many red cells Too many platelets Excessive fibrosis in the marrow secondary to a probable ET/PRV
What is the most common genetic mutation in MPNs?
JAK2 mutation
What is the clinical presentation of polycythaemia vera?
Signs Plethoric faces Palpable spleen Pruritis (aquagenic) after contact with warm water * Tendency to thrombose * tendency to bleed * HTN * Conjunctival suffusion * Engorged retinal vessels Symptoms * Headache * Dizziness * Blurred vision * dyspnoea * ‘full’ feeling in head
There are several causes of polycythaemia. Other than PRV what are they?
Hypoxia- normal physiological response to low oxygen, smoking, lung disease, cyanotic heart disease, altitude Fibroids Excessive EPO
What is the treatment of PV? What are the objectives of this treatment?
To reduce the risk of thrombosis and haemorrhage To minimise the risk of transformation to acute leukaemia and myelofibrosis. TREATMENT Venesection to Hct<0.45Anti-platelets treatment: aspirin 75mgHydroxycarbamide therapy for thrombocytosis
Is essential thrombothaemia more common men or women?When are the peaks in age?
Women50-55 and 30 in women
What are the clinical features of ET?
Mostly asymptomatic at diagnosisVascular events: thrombosis (arterial more common than venous)Microvascular occlusive symptoms * Erythromelagia * Acroparasthesia * digital ischaemia * Neurological symptoms: TIA, migraine-like headache, dizziness * Vision disturbances: transient blindness, blurred vision, photopsia * Bleeding >plts 1500 * Acquired vWD
What is the first line cytoreductive treatment in ET?
Hydroxycarbamide which acts as a ribonucleotide reductase inhibitor
What are the clinical features of myelofibrosis?
Marrow failure Splenomegaly Hepatomegaly Hypermetabolic symptoms Hyperuricaeniia
What is the stereotypical findings for myelofibrosis on a blood film?
Tear drop shaped RBCNucleated red cell
What treatment is advised for myelofibrosis?
Ruxolitinib an oral JAK inhibitor
Which disease is a type of myeloproliferative disease which results in accumulation of myeloid progenitors, a high WCC and a large spleen?
CML
What is the genetic diagnostic marker for CML? How is it made? What does it code for?
The Philadelphia chromosome of 9 and 22 translocation. The subsequent Bcr-Abl protein is responsible for CML.
What is the treatment for CML and what is its mechanism of action?
Imatinib which binds and inhibits the ATP binding site of the tyrosine kinase.