Myeloproliferative disorders Flashcards
What is polycythaemia?
Polycythaemia is described as a
Raised Hb [135-175]
Raised Haematocrit [0.41-0.53]
How do you differentiate between relative(pseudo) and true polycthaemia?
- Relative = same red cell mass, decreased plasma volume
2. True = Increased red cell mass, same plasma volume
What are causes of relative polycythaemia?
- Alcohol
- Obesity
- Diuretics
What are causes of secondary true polycythaemia?
Secondary (i.e. Reactive with a raised EPO)
i) Appropriate
- > High Altitude
- > Hypoxic Lung Disease
- > Cyanotic Heart Disease
- > High Affinity Haemoglobin
ii) Inappropriate
- > Renal Disease i.e. Cysts, Tumours & Inflammation
- > Uterine Myoma
- > Other tumours i.e. liver&lung
What are causes of primary true polycythaemia?
True Polycythaemia Primary (Low EPO) i) Philadelphia Chromosome Negative -> Polycythaemia Vera -> Idiopathic Erythryocytosis -> Essential Thrombocythaemia -> Primary Myelofibrosis
ii) Philadelphia Chromosome Positive
- > Chronic Myeloid Leukaemia
How does tyrosine kinase (specifically JK) normally result in cellular proliferation?
- > Growth Factor binds to receptor
- > Phosphorylation of the JAK’s
- > Activation of the STAT’s
- > Translocation to the nucleus and stimulate cellular proliferation
What does a mutation in the tyrosine kinase (JK) result in?
-> The signalling cascade is continously activated
Erythyroblast Mutation - Polycythaemia
Megakaryocyte Mutation - Thrombocytopenia
Granulocyte Mutation - Chronic Myeloid Leukaemia.
Define Polycythaemia vera
An increase in the production of red blood cell and surrounding plasma, often accompanied by a variable increase in platelets and granulocytic cells
Peaks at 60 years of age
What are the clinical features of polycythaemia vera?
-> Incidental diagnosis where there is a raised Hb and Hct. OR Symptoms of Blood Hyperviscosity -> Headaches, light headedness, stroke -> Visual disturbances -> Fatigue, dyspnoea Increased Histamine Release -> Aquagenic Pruritis -> Peptic Ulceration
What are the clinical signs of polycythaemia?
- > Splenomegaly 79%
- > Plethora - reddish complexion
- > Erythromelalgia i.e. red painful extremities
- > Thrombosis
- > Retinal vein engorgement
- > Gout increased RBC turnover, therefore increased Uric Acid
What are the investigations for polycythaemia vera?
FBC
- > Raised Hb
- > Raised Hct
- > Normal/Raised WCC
- > Normal/Raised Platelets
- > Low EPO
Film
-> No cirulating Immature cells
Genetic testing for JK mutation
What is the management of polycythaemia vera?
Aim to reduce HCT ie. <45% -> Venesection -> Cytoreductive therapy with Hydroxycarbamide (Chemotherapy) Aim to reduce thrombotic Risk -> Aspirin -> Keep Platelet count <400*10^9
Define Essential Thrombocythaemia
Chronic Myeloproliferative Neoplasm mainly involving the megakaryocytic lineage
-> Sustained Thrombocytosis i.e. platelets ( OVER 600*10^9)
Peaks at 55 years of age
What are the clinical features of Essential Thrombocythaemia?
-> 50% of cases are incidental on FBC OR Pro-Thrombotic -> Arterial ; CVA, Gangrene, TIA -> Venous ; PE, DVT OR Pro-Bleeding (get you a platelet that can do both x x x but seriously idk why) -> Mucous membranes cutaneous AND -> Headaches, Dizziness, Visual Field Disturbances -> Modest Splenomegaly
What is the management of Essential Thrombocythaemia?
Aspirin - Reduce Thrombotic Risk
Anagrelide - Inhibits platelet formation, however can accelerate myelofibrosis
Hydroxycarbamide - can accelerate leukaemia
Define Primary Myelofibrosis
- > A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytes.
- > ASSOCIATED WITH REACTIVE FIBROSIS and extramedullary haematopoiesis
7th decade of life
What are the clinical features of primary myelofibrosis?
-> 30% present Incidentally
Polycythaemia Vera or Essential Thrombocythaemia can progress to Primary Myelofibrosis
OR
-> Cytopenia i.e. anaemia/thrombocytopenia
-> Thrombocytosis
-> Massive Splenomegaly – Extramedullary Haematopoesis
-> Hepatomegaly – Budd-Chiari Syndrome
Hypermetabolic State i.e. Weight Loss, Fatigue, Night Sweats and Hyperuricaemia
What is Budd Chiari syndrome?
Budd-Chiari syndrome is a condition in which the hepatic veins (veins that drain the liver) are blocked or narrowed by a clot (mass of blood cells). This blockage causes blood to back up into the liver, and as a result, the liver grows larger.
What are the investigations for primary myelofibrosis?
Blood Film
- > Leucoerythroblastic Picture
- > Tear Drop Poikilocytes o.e. Dacrocyte
- > Giant Platelets
- > Circulating Megakaryocytes
Bone Marrow Aspirate
- > Dry Tap
- > Increased reticulin or collagen fibrosis
- > Prominent megakaryocyte hyperplasia
- > New bone formation
What is the management of primary myelofibrosis?
-> Supportive i.e. Transfusions of RBC and Platelets
these are often ineffective because of splenomegaly
-> Cytoreductive therapy i.e. Hydroxycarbamide
may help the thrombocytosis but worsen anaemia
-> Splenectomy
symptomatic relief, but may worsen condition in the long run
-> Ruxolotinib; JAK2 inhibitor
reserved for those with the worst prognosis
-> Allogenic Stem Cell Transplant
potentially curative
Define Chronic Myeloid Leukaemia
-> The cancer of the granulocyte precursor (Myeloblast) which results in the overproduction of Basophils, Neutrophils, Eosinophils etc.
40-60 years of age
What are the clinical features of Chronic Myeloid Leukaemia?
- > Lethargy
- > Hypermetabolism
- > Thrombotic event i.e. blindness, CVA secondary to leucostasis blood
- > May also present with bruising/bleeding
- > Hepatosplenomegaly
What are the investigations for Chronic Myeloid Leukaemia?
FBC
- > Hb and Platelets preserved if not raised; in Acute Leukaemias, you would see the Platelets/Erythrocytes drop.
- > MASSIVE leucocytosis
Blood Film
- > Neutro/Eosino/Baso-philia
- > No excess blast cells.
Genetic Testing
-> (9;22) Translocation produces the BCRABL fusion oncoprotein.
What is the 1st line treatment for Chronic Myeloid Leukaemia?
First Line - Imatinib, 95% 5 year survival.
Orally Active ABL Tyrosine Kinase Inhibitor, as a result it is not perpetually activated and inducing proliferation
