Chronic Myeloproliferative Disorders Flashcards
what is meant by myeloproliferative
abnormal proliferation of myelo cells in the marrow
what is definition of CMD
Clonal haemopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells
Maturation is PRESERVED
how does acute leukaemia and CMD differ on blood film
acute leukaemia - lots of primitive cells
MPD = numbers are increasing but do have normal maturations
how is CMD subdivided
BCR-ABL 1 negative
- idiopathic myelofibrosis
- essential thrombocythaemia (ET)
- Polycythaemia Rubra Vera (PRV)
BCR-ABL 1 positive
- CML [philadelphia chromsome]
what is the basic problem in ET
over production of platelets
what is the basic problem in PRV
over production of red cells
when should MPD be consider - in terms of blood results
High Granulocyte count ± High Red cell count / haemoglobin ± High Platelet count ± Eosinophilia/basophilia
Splenomegaly
Thrombosis in an unusual place
what is CML
Proliferation of myeloid cells
- Granulocytes & their precursors
- Other lineages (platelets)
Fatal without stem cell/bone marrow transplant in the chronic phase
what is the pathology of CML
chronic phase with intact maturation 3-5 years, followed by ‘blast crisis’ reminiscent of acute leukaemia with maturation defect
what are Sx of CML
asymptomatic splenomegaly hypermetabolic Sx gout Priapism [persistent and painful erection]
what might people complain of if they have splenomegaly
people feel hungry, and then they start eating and then they feel full quickly
what are lab finding of CML
normal/low Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis (too many platelets)
what is the hallmark of CML
philadelphia chromosome
what is philadelphia chromosome
part of one chromosome moving to another
Chr 22 gives some information to Chr 9
Makes the BCR-ABL 1 gene
what does the BCR-ABL 1 gene cause
tyrosine kinase which causes abnormal phosphorylation (signalling) leading to the haematological changes in CML
what is the Tx for CML
Imatinib
what are Sx are common to all BCR-ABL1 Negative MPD
Asymptomatic
Increased cellular turnover
- gout, fatigue, weight loss, sweats
Splenomegaly Sx
Marrow failure
Thrombosis
- arterial or venous including TIA, MI, claudication, erythromelalgia [thrombosis in hands and feet]
what are lab findings of PRV
High Hb accompanied by erythrocytosis (true increase in red cell mass)
Can also have an excessive production of other lineages
what must PRV be distinguished from
secondary polycythaemia - chronic hypoxia, smoking, bad asthma, erythropoietin-secreting tumour
pseudopolycythaemia -dehydration, diuretic therapy, obesity
what are features specific to PRV
- features common to MPD
- headache, fatigue
- itch (aquagenic puritis - patient has a shower and then have an uncontrollable itch for an hour or so)
what Ix must be done to PRV
JAK2 mutation status
what is JAK2 mutation in PRV
Mutation (substitution) results in loss of auto-inhibition
Activation of erythropoiesis in the absence of ligand
what is Tx for PRV
vensect to haematocrit < 4.45
Aspirin
Cytotoxic oral chemotherapy (eg Hydroxycarbamide)
what is ET
Uncontrolled production of abnormal platelets
- thrombosis
- at high levels can also cause bleeding due to acquired von Willebrand disease
what are Sx of ET
- Sx common to MPD
- vaso-occlusive complications
- Bleeding (unpredictable esp at surgery)
what should be excluded in ET
Exclude reactive thrombocytosis
- blood loss, inflammation, malignancy, iron deficiency
Exclude CML
what genetics mutations are tested in ET
JAK2 mutation - +ve in 50%
CALR (Calreticulin) - those w/out JAK2
MPL mutation
what is type last Ix in ET
Bone marrow aspirate
what is Tx of ET
Anti-platelet - Aspirin
Cytoreductive therapy to control proliferation
- hydroxycarbamide, anagrelide, interferon alpha
what is myelofibrosis
rare bone marrow cancer
proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue
what are the two mechanisms of myelofibrosis
Idiopathic
Post-polycythaemia or post-essential thrombocythaemia
what are features of IDIOPATHIC myelofibrosis
Marrow failure
Bone marrow fibrosis
Extramedullary haetopoiesis
what are the film appearances of idiopathic myelofibrosis
Leukoerythroblastic - precursors of white cells and red cells seen on blood film
what are characteristic about the shape of red blood cells in idiopathic myelofibrosis
Teardropped shaped RBCs
what are Sx of MF
Marrow failure
- anaemia, bleeding, infection
Splenomegaly
- LUQ abdo pain, portal hypertension
Hypercatabolism
what are IX of MF
blood film - tear-drop shaped RBC and leucoerythroblastic
dry aspirate - due to the scarring/fibrosis in the bone marrow
fibrosis on trephine biopsy
JAK2 or CALR mutation in a proportion
when are Leucoerythroblastic film seen
Reactive (sepsis)
Marrow infiltration
MF
what is the Tx of MF
Supportive care - blood transfusion, platelets, antibiotics
Allogeneic stem cell transplantation in a select few
Splenectomy
JAK2 inhibitors e.g. Ruxolitinib therapy
