Chronic Myeloproliferative Disorders Flashcards
What does proliferative mean?
To grow or multiple by rapidly producing new tissue, parts, cells or offspring
Describe myeloproliferative disorders
Clonal haemopoietic stem cell disorders with an increased population of one or more types of haemopoietic cells
Is maturation depleted or preserved?
Preserved
What is BCR-ABL1 +ve?
Chronic myeloid leukaemia
What is BCR-ABL -ve?
Idiopathic myelofibrosis
Polycythaemia rubra vera
Essential thrombocytopenia
When would you consider a myeloproliferative disorder?
High granulocyte count High red cell count/Hb High platelet count Eosinophilia/basophilia Splenomegaly Thrombosis in an unusual place
What is Chronic Myeloid Leukaemia? (CML)
Proliferation of myeloid cells
Granulocytes and their precursors and platelets
What is needed to help prevent CML from being fatal?
Stem cell / bone marrow transplantation in the chronic phase
What are the 3 phases of CML?
Chronic
Accelerated
Blast crisis
What are clinical features of CML?
Asymptomatic Splenomegaly Hypermetabolic symptoms Gout Problems related to hyperleucocytosis and priapism
What are lab features of CML?
Normal or reduced Hb
Leukocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
Bone marow changes
What is the chromosome, the gene and the product which causes the abnormal phosphorylation (signalling) leading to the haematological changes seen in CML?
Chromosome = Philadelphia chomosome (22) Gene = BCR-ABL1 Product = Tyrosine kinase
What can be used to treat CML?
Imatinib
Describe Polycthaemia rubra vera? (PRV)
High haemoglobin / haematocrit accompanied by arythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages
Describe secondary polycythaemia?
Chronic hypoxia
Smoking
Erythropoietin-secreting tumour
Describe pseudopolycthaemia?
Dehydration
Diuretic therapy
Obesity
What are clinical features of PRV?
Clinical features common to MPD?
Headache
Fatigue
Itch (aquagenic puritis)
What happens with the Philadelphia chromosome?
22 and 9 swap some bits of information
Translocation
How do you investigate polycthaemia?
History
Examination
FBC + film
JAK2 mutation status
Describe JAK2?
It’s a kinase
Mutation present in over 95% of PRV patients
Substitution results in loss of auto-inhibition
Activation of erythropoiesis in the absence of ligand
What are some infrequent tests for polycythaemia?
Erythropoietin levels
Bone marrow biopsy
What are investigations for secondary polycythaemia?
CXR
O2 saturations
Arterial blood gas
Drug history
What is the treatment for PRV?
Vensect to haemocrit <0.45
Aspirin
Cytotoxic oral chemo (e.g. hydroxycarbamide)
Describe ET
Uncontrollable production of abnormal platelets with abnormal function
Thrombosis
Can cause bleeding due to acquired von Willebrand disease
What are clinical features of ET?
Common to MPD (esp. vasooclusive complications
Bleeding
How do you diagnose ET?
Exclude reactive thrombocytosis Exclude CML Genetics: JAK2 (50%) CALR (calreticulin) MPL Bone marrow appearances
How do you treat ET?
Anti-platelet agents (aspirin)
Cytoreductive therapy to control proliferation - hydroxycarbamide, anagrelide, interferon alpha
What can myelofibrosis be?
Idiopathic
Agnogenic myeloid metaplasia
Post-polycythaemia or essential thrombocythaemia
Describe idiopathic myelofibrosis?
Marrow failure Bone marrow fibrosis Extramedullary hematopoiesis Leukoerythroblastic Teardrop-shaped RBC's in peripheral blood
What are clinical features of myelofibrosis?
Marrow failure - anaemia, bleeding, infection
Splenomegaly - LUQ pain, portal hypertension
Hypercatabolism
How do you diagnose myelofibrosis?
Typical blood film (tear-drop shaped RBC and leucoerythroblastic)
Fibrosis on trephine biopsy
JAK2 or CALR mutation
What are a leucoerythroblastic film ?
Reactive (sepsis)
Marrow infiltration
Myelofibrosis
How do you treat myelofibrosis?
Supportive care (blood transfusion, antibiotics)
Allogenic stem cell transplantation in select few
Splenectomy
JAK2 inhibitors
What counts as abnormal platelets?
Infection increase
Iron deficiency
Malignancy
Blood loss
