Myeloproliferative disorders Flashcards
What are myeloproliferative disorders?
Myeloproliferative dysorders are a sub-group of haematological malignantcies of myeloid cells, with normal blast cells
Examples include
1. Polycythemia vera (erythroid)
2. Essential thrmocythaemia (megakaryocyte)
3. Primary myelofibrois and
4. CML
What are the philadelphia choromosome posisitve and negative myeloproliferative disorders?
Philadelphia positive: CML
Philadelphia negative
1. Polycythemia vera
2. Essential Thrombocytaemia
3. Primary Myeloid fibrosis
What is polycythemia?
Raise in Hb concentration and Haematocrit %
if Hb >175
Haemmatocrit >0.53
What are differentials for polycythemia?
- Relative (lack of plasma) - pseudo
- Reactive (Secondary), e.g. long-term lung disease (increased EPO)
- Proliferative (primary) - Polycythemia Vera
How can you differentiate between pseudo - and true polcythemia?
Pseudo/ Relative = decrease in plasma volume leads to polycythemia on blood (e.g. alcohol, obesity, diuretics)
True = Red cells truely increased
Differentiate between them can be hard clinically
What systemic conditions can be cause of reactive polycythemia?
Secondary Polycythemia –> due to high EPO
- Appropriately = low oxygen
* high altitiude
* hypoxic lung disease
* cyanotic heart disease
* high affinity haemoglobin (in Hb mutations) - Non-appropriately
* renal disease
* uterine myoma
* other tumours (paraneoplastic syndrome)
What is the pathophysiology of polycythemia rubra vera?
Myeloproliferative disorder with primary malignancy and prolifertion of Red blood cells
- Due to point mutation inJAK 2 (V617F)
- Gain of function mutation of tyrosikne kinase receptor (important in signaling for haematopoiesis)
- Leading to hyperviscocity, hypervolaemia / hypermetabolism
What is the clinical precentation of polycythemia rubra vera?
- often asymptomatic and incidental findings on bloods
But otherwise
- Hyperviscocity syndrome: triad of mucosal bleeding, neurological symptoms, and visual changes
- Plethora: flushed face with cyanotic lips (due to absolute increse in deoxy Hb, even though relatively normal % of doxy Hb)
- Puritus (with warm water –> histamine release - can also cuase peptic ulcers)
- Hypertension
- Hepato-splenomegaly
- gout (due to increased break-down)
What are the gentic mutations most commonly involved in philadelphia-chromosome negative myeloproliferative disorders?
- Polycythemia Vera
- Essential thrombocytohelia
- Primary Myeloid Fibrosis
What is the epidemiology of Polycythemia Vera?
- Annual incidence 2-3/ 100.000
- Slightly more in males 1.2:1
- Mean age at diagnosis 60 years
- 5% below age of 40 years
What is the managmement of Polycythemia?
Overall aim to reduce HCT due to increased risk of stroke
- venesection (especially if veins are good enough)
- cytoreductive therapy hydroxycarbamide –> suppress cell devision
Also controls platelets (can also be higher)
What is essential thrombocythaemia?
What is the epidemiology?
Chronic Myeloproliferative disorder mainly involving megakaryocytic/ platelt lineage
- sustained thrombocytosis (>600)
- incidence 1.5/ 100.000
- Bimodal age distribuation –> 55 and 30
What investigations should be done for the diagnosis of Polycythemia Vera?
- FBC for Hb and Hct
- EPO levels (primary vs. secondary)
- test for JAK 2 mutation –> is positive = polycythemia
What is the clinical presenation of essential polycythaemia?
- Thrombosis: arterial and venous
- Bleeding: mucous membranes and cutaneaous (majority of new platelets are disfunctional)
- Headaches, visual distubances
- modest splenomegaly
What is the management of Essential Thrombocythaemia?
Overall aim: reduce risk of strokes
1 . Aspirin
2. Hydroxycarbamide (reduced prodction of cells)
What is the prognosis of Essential thrombocythaemia?
- Normal life expecancy
- Risk of leukaemic transformation 5% in >10 years
- Myelofibrosis might occur but rarely
What is primary myelofibrosis?
Cloncal myeloproliferative disease associated with reactive bone marrow fibrosis
–> due to production of fibroblast stimmulating factors –> fibrosis
Clinical presentation is triad og
1. Bone marroy fibrosis –> cytopenia (+/- thrombocytosis)
2. Extramedullary haematopoieisis –> Splenomegaly (Massive Hepato-splenomegaly)
3. Hypermetabolic state (B-symptoms + hyeruricaemia)
What is Budd-Chiari syndrome?
Budd-Chiari syndrome
- hepatic vein obstruction that leads to hepatomegaly, ascites, and abdominal discomfort
- most commonly due to a thrombotic occlusion secondary to a chronic myeloproliferative neoplasm (e.g., polycythemia vera)
How is primary myeloid fibrosis diagnosed?
- FBC - usually pancytopenia, can have increase in all lineages
- blood film: Leucoerythroblastic picture + tear drop poikilocytosis
- Bone Marrow . Dry tap –> trephine: shows collagen deposition
What is the managment of primary myelofibrosis?
Limited range of options + overall poor prognosis
- Supportive: RBC and platelet transfusion often ineffective because of splenomegaly
- Cytoreductive therapy: hydroxycarbamide (for thrombocytosis, may worsen anaemia)
- Ruxolotinib: JAK2 inhibitor (high prognostic score cases)
- Allogeneic SCT (potentially curative reserved for high risk eligible cases)
What is the prognosis of primary myelofibrosis?
Median 3-5 years but very variable
Bad prognostic signs
- Severe anaemia under 100g/L
- Thrombocytopenia under 100x109/l
- Massive splenomegaly
Prognostic scoring system (DIPPS)
- Score 0 – median survival 15years
- Score 4-6– median survival 1.3 years
What are the 2 main differentials for Massive hepato-splenomegaly with no lymphadenopathy?
- CML (infiltration)
- Primary myelofirbosis (due to extra-medullary haematopoiesis)
