Myeloproliferative disorders Flashcards
what does marrow have
granulocytes
red cells
platelets
what kind of disorders are myeloproliferative disorders
clonal haemopoietic stem cell disorders with an increased poduction of one or more cell types of haemopoietic cells
difference between myeloproliferative disorders and acute leuk
maturation is relatively preserved
classification of MPD
BCR-ABL1 pos:
chronic myeloid leuk - over production of granulocytes. philadelphia chromosome
BCR-ABL1 neg:
idiopathic myelofibrosis - scarring of th bone marrow and fibrosis
polycythaemia ruba vera -pver poroduction of red cells
essential thrombocytopenia - over production of platelets
when is MPD considered
high granulocyte +/- high red cell count/Hb +/- high platelet count +/- eosinophilia/basophilia
splenomegaly
thrombosis in an unusual place
no reactive explanation for any of these
what is chronic myeloid leuk
prolif of myeloid cells - grnaluocytes and their precursors and other lineages (platelets)
why is CML fatal
fatal without stem cell/bone marrow transplantation in the chronic phase
phases of CML
chronic phase with intact maturation for 3-5 years
accelerated phase
blast crisis - reminiscent of acute leuk with maturation defect
CML clinical features
asymp
splenomegaly - get full quick
hyper metabolic symptoms - gout, bone pain, sweats
misc: problems related to hyperleucocytosis problems, priapism
lab features of CML
normal/decreased Hb
leucocytosis with neutrophilic and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
marrow of CML
increase in neutrophils, myelocytes, eosinophils, basophils and basophil precursors
hallmark of CML
philadelphia chromosome
reciprocal translocation between 9 and 22
Leads to a new mixture of genes called BCRABL
genetics of CML
BCR-ABL1 produces tyrosine kinase which causes abnormal phosphorylation which leads to haematological changes in CML
genetics of CML and treatment
durable disease responses with tyrosine kinase inhibitor - imatinib
features of neg MPD
asymp gout, fatigue, weight loss splenomegaly marrow failure - fibrosis or leukaemia transfusion thrombosis
what can marrow failure lead to
acute leuk state
PRV is what
high hb and haematocrit
erythrocytosis
dominant effect is on red cells but can have an increased platelet count
secondary polycythaemia
chronic hypoxia
smoking
erythropoietin secreting tumour
pseudopolycyhtaemia
dehydration
diuretic therapy
obesity
true polycythaemia
false polycythaemia
red cell has increased
plasma has shrunk giving the impression that the Hb is high but it actually isn’t
PRV clinical features
common to MPD
headache, fatigue (remember blood viscosity has increased not plasma viscosity)
itch (aquagenic pruritus) - after a shower
investigation of polycythaemia
history
exam - people with secondary poly won’t have splenomegaly
FBC, film
JAK2 mutation status
JAK2 is what
kinase
present in over 95%of PRV px
mutation results in loss of auto inhibition
activation of erythro all the time
part of initial screening
treatment of PVR
venesct to haemocrit to <0.45
aspirin - reduce thrombotic risk
cytotoxic oral chemo - hydroxycarbamide
essential thrombocytopenia
uncontrolled production of abnormal platelets
thrombosis
at high levels can cause bleeding due to acquired von willebran disease
clinical features of ET
similar to MPD esp vasooclusive complications
bleeding
ET dx
exclude reactive thrombocytosis - blood loss, inflam, malig, iron defic
exclude CML
genetics :
JAK2 (in 50%)
CALR in those without mutant JAK2
MPL mutation
bone marrow
ET treatment
anti platelet - aspirin
cytoreductive therapy to control prolif - hydroxycarbamide, anagrelide, interferon alpha (last line)
myelofibrosis
idiopathic
secondary:
post polycthaemia or ET which progresses to marrow failure
IM features
marrow failure bone marrow fibrosis extra medullary haematopoiesis (liver and spleen) leukocerythoblastic film appearance teardrop shaped RBCs in peripheral blood
IM clinical features
marrow failure - anaemia, bleeding, infection
splenomegaly - LUQ pain, complication such as portal htn
hyper catabolism - anorexia, weight loss
features of MPD
IM lab dx
typical blood film - tear drop RBC and leucoerythroblastic
dry aspirate
fibrosis on trephine biopsy
JAK2 or CALR mutation
causes of leucoerythroblastic
reactive - sepsis
marrow infiltration - cancer
myelofibrosis
IM rx
supportive care - blood transfusion, platelets, ABs
allogeneic stem cell trabsplantion in a few px <50s
splenectomy - controversial
JAK2 inhibitors - improve spleen size, quality of life and possibly survival
high white cell count
infection
post surgery
steroids
high platelets
infection iron defic malig blood loss splenectomy
high red cells
dehydration - diuretics
pseudoplycythaemia
secondary polycythaemia - hypoxia induced etc
