Chronic Myeloproliferative Disorders Flashcards
What is a chronic myeloproliferative disorder?
Clonal haemopoietic stem cell disorder with increased production in one or more types of haemopoietic cells
Subtypes of MPDs?
BCR-ABL 1 positive
BCR-ABL 1 negative
A BCR -ABL positive disorder?
Chronic myeloid leukaemia
What are BCR-ABL 1 negative disorders?
Polycythaemia rubra Vera
Essential thrombocythaemia
Idiopathic myelofibrosis
What happens in CML?
Proliferation of myeloid cells - granulocytes
Clinical features of CML?
Asymptomatic
Splenomegaly
Hyper metabolic symptoms
Gout
What cells are raised in CML?
Leucocytosis with neutrophilia
Significant genetics in CML?
Philadelphia chromosome -> BCR -AML 1.
Gene product is tyrosine kinase causing abnormal phosphorylation -> haematological changes
Treatment of CML?
Stem cell transplant
Tyrosine kinase inhibitors - imatinib
What happens in polycythaemia rubra Vera?
Over production of red cells
High or low Hb in PRV?
High
Clinical features of PRV?
Increased cellular turnover -> gout, fatigue, sweats, weight loss Splenomegaly Thrombosis Itch Marrow failure Headache
Treatment of PRV?
Venesect to haematocrit <0.45
Aspirin
Hydroxycarbamide
What happens in essential thrombocythaemia?
Uncontrolled proliferation of abnormal platelets
Features of ET?
Bleeding Thrombosis Marrow failure Splenomegaly Asymptomatic Increased cellular turnover -> gout, fatigue, sweats, weight loss
Potential genetic links to ET?
JAK2 mutation
CAL2
MPL mutation
Treatment of ET?
Aspirin
Cytoreductive therapy - hydroxycarbamide , anagrelide , interferon alpha
Features of idiopathic myelofibrosis?
Marrow failure Bone marrow fibrosis Extramedullary haematopoiesis Leukoerythroblastic film appearances Teardrop shaped RBCs in peripheral blood
Clinical features of idiopathic myelofibrosis?
Marrow failure -> anaemia, bleeding, infection Splenomegaly Hyper catabolism Increased cellular turnover Thrombosis
Lab features in idiopathic myelofibrosis ?
Teardrop shaped RBC Leukoerythoblastic film Dry aspirate Fibrosis on trephine biopsy JAK2 or CALR mutation in some
Treatment of idiopathic myelofibrosis?
Supportive - blood transfusion , platelets, antibiotics
allogenic stem cell transplantation
?splenectomy
?JAK2 inhibitors
