Chronic Myeloproliferative Disorders Flashcards
what is meant by myeloproliferative
abnormal proliferation of myeloma cells in the marrow
e.g. granulocytes, red cells + platelets
what are myeloproliferative disorders
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 myeloproliferative disorder differ on blood film
acute leukaemia = lots of primitive cells
MPD= numbers are increasing but normal maturation
subdivisions of chronic myeloproliferative disorder
BCR-ABL 1 negative
BCR- ABL 1 positive
conditions that are BCR-ABL 1 negative
myelofibrosis
essential thrombocytosis (over-production of platelets)
polycythaemia rubra vera (overproduction of red cells)
conditions that are BCR-ABL 1 positive
Chronic myeloid leukaemia
- over production of granulocytes
- philadelphia chromosome
what is essential thrombocytosis
over production of platelets
what is polycythaemia rub vera
over production of red cells
when should you consider a myeloproliferative disorder
- high granulocyte count
- high RBC count / Hb
- high platelets count
- eosinophilia/basophilia
- splenomegaly
- thrombosis in an unusual place
what is chronic myeloid leukaemia
proliferation of myeloid cells
- granulocytes + their precursors (eosinophils, basophils, neutrophils)
- other lineages (platelets)
fatal without stem cell/bone marrow transplant
pathology of chronic myeloid leukaemia
chronic phase with intact maturation 3-5 years
followed by ‘blast crisis’- similar to acute leukaemia with maturation defect
clinical features of chronic myeloid leukaemia
asymptomatic splenomegaly hyper metabolic symptoms gout priaprism
what might people complain of in splenomegaly
feel hungry but get full very quickly when they start eating
lab findings in chronic myeloid leukaemia
normal/low Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes)
eosinophilia, basophilia
thrombocytosis (increased platelets)
+ve BCR- ABL gene
+ve philadelphia chromosome
hallmark of chronic myeloid leukaemia
philadelphia chromosome
what is a Philadelphia chromosome
part of one chromosome moving to another
chr 22 gives some info to chr 9
makes the BCR-ABL 1 gene
what does the Philadelphia chromosome result in
formation of new gene BCR-ABL 1
what does the BCR- ABL 1 gene cause
tyrosine kinase which causes abnormal phosphorylation (signalling) leading to haematological changes in chronic myeloid leukaemia
treatment of chronic myeloid leukaemia
Imatinib (tyrosine kinase inhibitor)
common features of myeloproliferative disorders
- myelofibrosis
- essential thrombocytosis
- PRV
increased cellular turnover (gout, fatigue, weight loss, sweats)
splenomeglay
marrow failure
thrombosis
- arterial/venous including TIA, MI, claudication, erythromelalgia
what is erythromelalgia
thrombosis in hands + feet
findings in polycythaemia rubra vera (PRV)
HIGH HB/haematocrit accompanied by erythrocytosis (a true increase in red cell mass)
what is erythrocytosis
true increase in red cell mass
what must polycythaemia rubra vera be distinguished from
secondary polycythaemia
pseudopolycythaemia
causes of secondary polycythaemia
hypoxia
- copd
- smoking
- altitude
Inappropriate EPO production
erythropoietin secreting tumour
- liver, renal, cerebellar
pseudopolycythaemia
decreased plasma volume therefore relative increase in concentration caused by: dehydration diuretic therapy obesity
specific features of PRV
itch – aquagenic puritis - patient has a shower and then has an uncontrollable itch
splenomegaly (do not get with secondary/pseudo)
increased WBC + platelets (usually normal in secondary/pseudo)
what is raised in PRV: blood viscosity or plasma viscosity
BLOOD VISCOSITY
What investigation must be done in PRV
JAK2 mutation status
what is a JAK2 mutation
JAK2 is a kinase
mutations present in over 95% of PRV
effects of JAK2 mutation
loss of auto-inhibition
activation of erythropoiesis in the absence of ligand
treatment of PRV
venesection to get haematocrit <0.45
aspirin
cytotoxic oral chemotherapy
example of cytotoxic oral chemo drug used in PRV
hydroxycarbamide
what is essential thrombocytosis
uncontrolled production of abnormal platelets
- thrombosis
- high levels can cause bleeding — acquired von willebrand
clinical features of essential thrombocytosis
bleeding
vaso-occlusive complications
what should be excluded in essential thrombocytosis
exclude reactive thrombocytosis
- blood loss, inflammation, malignancy, iron deficiency
(this is more common)
what genetic mutations are tested in essential thrombocytosis
JAK2- +ve in 50%
CALR mutation
MPL mutation
treatment of essential thrombocytosis
anti-platelet – aspirin
cytoreductive therapy to control proliferation
- hydroxycarbamide
- interferon alpha
what is myelofibrosis
clonal proliferation of abnormal megakaryocytes that release fibroblast stimulating factors e.g. PDGF (platelet derived growth factor)
this leads to myelofibrosis
what fibroblast stimulating factor is high in myelofibrosis
Platelet derived growth factor- PDGF
features of myelofibrosis
marrow failure – anaemia, infections, bleeding
extra medullary haemopoiesis – massive splenomegaly
hyper metabolism – weight loss, fever, sweats, fatigue
film appearances of idiopathic myelofibrosis
leukoerythroblastic
- precursors of white cells and red cells seen on blood film
characteristic shape of red blood cells in idiopathic myelofibrosis
teardrop shaped RBCs in peripheral blood
symptoms of myelofibrosis
Marrow failures
- anaemia
- bleeding
- infection
splenomegaly
- LUQ pain
- portal hypertension
Hypermetabolism
investigations + findings of myelofibrosis
blood film - tear drop RBCs
dry aspirate- due to the scarring/fibrosis in the bone marrow
fibrosis on trephine biopsy
JAK2 or CALR mutation
causes of a leucoerythroblastic film
reactive (sepsis)
marrow infiltration
myelofibrosis
treatment of myelofibrosis
supportive
- blood transfusion
- platelets
- antibiotics
allogenic stem cell transplantation
JAK2 inhibitors
what common drug can cause increased neutrophils
steroids - disrupts margination and causes redistribution
what physiological state can increase neutrophils
pregnancy
reactive causes of thrombocytosis
infection chronic inflammation e.g. RA/IBD anaemia hyposplenism haemorrhage
why is gout seen in myeloproliferative disorders
increased cell turnover + increased uric acid production
symptoms due to increased blood viscosity in polycythaemia vera
headache
tinnitus
visual disturbance
