Myeloproliferative Neoplasms Flashcards
What does myeloproliferative mean?
Myelo = bone marrow lineage Proliferative = to grow or multiply by rapidly producing mew tissue
What is a clonal haemopoietic stem cell disorder?
Increased production of one or more types of haemopoietic cells
Describe CML
Overproduction of granulocytes
BCR-ALB 1 positive = philadelphia chromosome
Describe essential thrombocythaemia?
Over-production of platelets
Describe polycythaemia vera
Overproduction of red cells
What are the different types of BCR-ABL 1 negative myeloproliferative neoplasms?
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythemia
When should a MPN be considered?
High granulocyte count High red cell count/ Hb High platelet count Eosinophilia/ basophilia Splenomegaly Thrombosis in an unusual place With NO reactive explanation
What are the different phases of CML?
Chronic phase
Accelerated phase
Blast crisis
What are the clinical features of CML?
Asymptomatic Splenomegaly Hypermetabolic symptoms Gout Misc; problems related to hyperleucocytosis, priapism
What are the lab features of CML?
Normal/ decreased Hb
Leucocytosis with neutrophilia and myelocytes, eosinophila, basophilia and thrombocytosis
What is the hallmark of CML?
Philadelphia chromosomee
What is the treatment for Philadelphia chromosome positive CML?
Tyrosine kinase inhibitor - imatinib
What are features common to MPN?
Asymptomatic
Increased cellular turnover (gout, fatigue, wt loss, sweats)
Sy/si due to splenomegaly
Marrow failure; fibrosis or leukaemia transformation; PRV and ET
Thrombosis; TIA, MI, abdo vessel, claudication, erythomelagia
What is polycythaemia vera?
High Hb accompanied by erythrocytosis (a true increased in red cells mass) but can have excessive production of other lineages
What do you NEED to distinguish PV from?
Secondary polycythaemia; chronic hypoxia, smoking, epo-secreting tumour
Pseudopolycythaemia; dehydration, diuretic therapy, obesity
What are the clinical features of PV?
Similar to MPN
Headache, fatigue (blood viscosity raised NOT plasma viscosity)
Itch; aquagenic puritis
What are the investigations required for PV?
History - investigate for secondary causes (CXR, O2, ABG, drug hx)
Exam; splenomegaly
FBC, film
JAK2 mutation
What is the most important test for PV?
JAK2 mutation
What is JAK2?
Kinase
Results in loss of auto-inhibition and activation of epo in the absence of a ligand
What is now part of the initial screening in PV?
Mutational analysis
What is the treatment for PV?
Venesect to haematocrit of <0.45
Aspirin
Cytotoxic oral chemo; hydroxycarbamide
What is ET?
Uncontrolled proliferation of abnormal platelets
Platelet function ABNORMAL; thrombosis, at high levels can cause bleeding due to acquired vWF disease
What are the clinical features of ET?
Common MPN, particularly vasoocclusive
Bleeding
How is ET diagnosed?
Exclude reactive thrombocytosis - IMPORTANT
Exclude CML
What are the genetics of ET?
JAK2 in 50-60%
CALR in 25%
MPL in 5%
10-20% triple neg
What is the treatment for ET?
Anti-platelets; aspirin
Cytoreductive therapy to control proliferation; hydroxycarbamide, anagrelide or interferon alpha
What can cause myelofibrosis?
Idiopathic
Post-polycythaemia or essential thrombocythaemia
What are the features of idiopathic myelofibrosis?
Marrow failure; variable degrees Bone marrow fibrosis Extramedullary haematopoiesis (liver and spleen) Leukoerythroblastic film appearances Tear-drop shaped RBC in peripheral blood
What are the features of marrow failure?
Anaemia
Bleeding
Infection
What are the features of splenomegaly?
LUQ pain
Cx; portal hypertx
Gastric fullness
What are the clinical features of myelofibrosis?
Marrow failure
Splenomegaly
Hypercatabolism
How is MF diagnosed in the lab?
Typical blood film; tear drop shaped RBC and leukoerythroblsatic
Dry aspirate
Fibrosis on trephine biopsy
What are causes for a leukoerythroblastic film?
Reactive (sepsis)
Marrow infiltration
Myelofibrosis
What is a leukoerythroblastic film?
Immature cells (myelocytes and normoblasts) seen on the peripheral blood film Normoblast = nucleated RBC
What is the treatment of MF?
Supportive care; blood transfusion, platelets, antibiotics
Allogenic stem cell transplantation
??Splenectomy
JAK2 inhibitors (ruxolitinib)
What are the causes for reactive high blood coutns?
Reactive granulocytes; infection (pyogenic bacteria causing neutrophilia), physiological (post-surgery, steroids)
Reactive thrombocytosis; infection, IDA, malignancy, blood loss
Reactive polycythaemia; dehydration (pseudopolycythaemia), secondary
