Myeloproliferative Neoplasm Flashcards
Define myeloproliferative neoplasm
Clonal haemopoietic stem cell disorders which an increased production of one or more types of haemopoietic cells
How is MDN different to leukaemia?
Results in overproduction of mature differentiated cells
Describe the appearance of acute leukaemia microscopically
Monomorphic appearance with large cells and big nuclei - primitive cells
Describe the appearance of MPN microscopically
Lots of nucleated cells - hypercellular, variety of cells at different stages of maturation
Name the two subtypes of MPN
BCR ABL 1 positive
BCR ABL 1 negative
What disease is BCR ABL 1 positive?
Chronic myeloid leukaemia - overproduction of granulocytes
What diseases are BCR ABL 1 negative?
Polycythaemia vera
Essential thrombocytopenia
Primary myelofibrosis
What blood results would suggest MPN?
High granulocyte count High red cell count/Hb High platelets Eosinophilia/Basophilia Splenomegaly Thrombosis in unusual place
What is chronic myeloid leukaemia?
Proliferation of myeloid cells
Name the phases of chronic myeloid leukaemia
Chronic
Accelerated
Blast
Describe the chronic phase of CML
Predominantly mature cells - intact maturation followed by a blast crisis similar to acute leukaemia with maturation defect
Describe the accelerated phase of CML
Transition phase, high proportion of less mature cells
State the clinical features of CML
Asymptomatic Splenomegaly (LUQ discomfort, early satiety) Hypermetabolic syndrome Gout Priapism - hyperleukocytosis
Name the investigations done in CML
Blood count and film
Bone marrow sample
Philadelphia chromosome
Describe the blood film in CML
Normal/reduced Hb, leukocytosis with neutrophilia
Myeloid precursors, eosinophilia, basophilia, thrombocytosis
What will a bone marrow sample in CML look like?
Increased cellularity
Increased granulocytes
What is the philadelphia chromosome?
Translocation chromosome
Results in fusion of ABL gene and BCR gene on chromosome 11 - tyrosine kinase which causes abnormal phosphorylation
How is CML treated?
Tyrosine Kinase Inhibitor
What are the common features of BCR ABL 1 negative MPNs?
Asymptomatic Increased cellular turnover - gout, fatigue, weight loss, sweats Splenomegaly Marrow failure Thrombosis Erythromelagia
What is erythromelagia?
Pain in hands and feet due to microvascular occlusion
What is polycythaemia vera?
MPN characterised by high Hb and haematocrit accompanied by erythrocytosis
Describe the difference between a true and pseudo polycythaemia
True - increase in proportion of red cells
Pseudo - normal red cells but reduced plasma volume causes increased Hct
What causes secondary polycythaemia?
Hypoxia
Smoking
Tumours - erythropoietin secreting
What causes pseudopolycythaemia?
Dehydration
Obesity
Diuretics
State the features of polycythaemia vera
Headache
Fatigue
Itch - aquagenic puritis
How is polycythaemia vera investigated?
FBC, blood film, look for secondary cause
JAK2 mutation - results in loss of auto-inhibition activation of erythropoiesis in the absence of ligand
How is JAK2 mutation identified?
Genetic analysis of peripheral blood
Describe the treatment of polycythaemia vera
Prevent thrombosis
- venesect to haematocrit
- aspirin
Cytotoxic chemotherapy
What is essential thrombocythaemia?
Over production of abnormal platelets
Why can essential thrombocythaemia cause bleeding?
Acquired Von Willebrand disease - vWF absorbed onto the surface of abnormal platelets and reduces expression
Name the clinical features of essential thrombocythaemia
Vaso-occlusive complications
Bleeding
What diseases can present like essential thrombocythaemia?
CML
Reactive thrombocytosis
How do you investigate essential thrombocythaemia?
Genetics - JAK2, CALR, MPL
Bone marrow - increased and abnormal megakaryocytes
How is essential thrombocythaemia treated?
Anti-platelet aspirin
Cytoreductive therapy to control proliferation -
- hydroxycarbamide, IFN alpha
State the characteristics of myelofibrosis
Marrow failure Bone marrow fibrosis Extramedullary hematopoiesis Leukoerythroblastic film Teardrop RBC
What are the clinical features of myelofibrosis?
Marrow failure
Splenomegaly
Hypercatabolism
How is myelofibrosis diagnosed?
Blood film
Dry aspirate/trephine biopsy
Genetics
What classical RBC shape is seen on blood film?
Poikilocytes teardrop RBC in peripheral blood
What is leukcoerythroblastic film?
Presence of neutrophil and red cell precursors in the peripheral blood
What causes leukcoerythroblastic film?
Reactive - sepsis
Marrow infiltration
Myelofibrosis
What will a trephine biopsy of myelofibrosis show?
Loss of fat spaces and dense network of reticulin fibres
How is myelofibrosis treated?
Supportive - transfusion, antibiotics
Allogenic stem cell transplant - potentially curable
Splenectomy
JAK 2 inhibitor
