Myeloproliferative Disorders Flashcards
what are myeloproliferative disorders?
group of haematopoietic stem cell conditions occurring due to uncontrolled proliferation of a single type of stem cell
what do all types of myeloproliferative disorder have in common?
all have mutations which continuously activate JAK2
what is JAK2?
enzyme which stimulates production of RBCs, WBCs and platelets
usually only activated when additional blood cell production needed such as during inflammation, hypoxia or certain blood malignancies
are myeloproliferative disorders considered cancer?
yes
type of bone marrow cancer
what genetic mutations can be associated with myeloproliferative disorders?
JAK2
MPL
CALR
possible complication of myeloproliferative disorders?
have potential to progress and transform into acute myeloid leukaemia (AML)
types of myeloproliferative disorders?
primary myelofibrosis
polycythaemia vera
essential thrombocythaemia
what is myelofibrosis?
least common and most aggressive myeloproliferative disorder
where proliferation of the cell line leads to fibrosis of the bone marrow (bone marrow replaced by scar tissue)
what can cause myelofibrosis?
can occur on its own (primary myelofibrosis)
can be result of progression from polycythaemia vera or essential thrombocythaemia
what happens in myelofibrosis?
proliferation of cell line
proliferating cells release cytokines such as fibroblast growth factor causing fibrosis of bone marrow
fibrosis affects production of blood cells and can lead to anaemia, low WBCs etc
possible complications of myelofibrosis?
when bone marrow is replaced by scar tissue, blood cell production starts to happen in other places such as liver and spleen (extra-medullary haematopoiesis) leading to hepatosplenomegaly
this can cause portal hypertension or spinal cord compression if it occurs around the spinal cord
possible symptoms of myelofibrosis?
can have hepatomegaly or splenomegaly or both
can have portal hypertension
variable changes in RBC, WBC and platelet count
can have symptoms of spinal cord compression
FBC features of myelofibrosis?
anaemia
can have high or low WBCs (leukocytosis or leukopaenia)
can have high or low platelets (thrombocytosis or thrombocytopenia)
blood film features of myelofibrosis?
teardrop shaped RBCs
varying sizes of RBCs (poikilocytosis)
immature RBCs and WBCs (blast cells)
possible complications of myelofibrosis?
can progress to AML
how is myelofibrosis managed?
can just be monitored if mild disease
allogenic stem cell transplant (can cure but carries risks)
chemo (can control disease and help symptoms but not curative)
supportive management of anaemia, splenomegaly, portal hypertension etc
what is polycythaemia vera?
result of proliferation of erythroid cell line (excessive production of normal RBCs)
which is the most common myeloproliferative disorder?
polycythaemia vera
3 key signs of polycythaemia vera on examination?
conjunctival plethora (very red as lots of RBCs unlike anaemia where theyd be pale)
ruddy complexion
splenomegaly (as spleen filters RBCs)
blood features of polycythaemia vera?
increased RBC production
raised Hb
complications of polycythaemia vera?
arterial or venous thrombosis due to hyperviscosity as a result of increased RBCs
TIAs
migraine
aquagenic pruritis
bleeding or pseudohyperkalaemia (due to extreme thrombocytosis)
splenomegaly
can transform into myelofibrosis which can cause bone marrow failure and acute leukaemia
how is polycythaemia vera managed?
venesection = first line
aspirin can reduce risk of blood clots
chemo can help control proliferation
what is essential thrombocythaemia?
proliferation of the megakaryocyte line (platelets)
blood features of essential thrombocythaemia?
increased platelets (thrombocytosis) alone - usually have platelet count >600
diagnosis of essential thrombocythaemia?
diagnosis of exclusion
thrombocytosis is common in all myeloproliferative disorders but if thats the only abnormality then its probs essential thrombocythaemia
complications of essential thrombocythaemia?
TIA
migraine
burning pains in hands and feet
bleeding or pseudohyperkalaemia
can have thrombosis or splenomegaly but rare
some patients can progress to myelofibrosis - bone marrow failure or AML
lifespan in essential thrombocythaemia?
normal
how is essential thrombocythaemia managed?
aspirin can reduce clot risk
chemo can control disease
test of choice for diagnosing myeloproliferative disorders?
bone marrow biopsy
(cant really do bone marrow aspiration as bone marrow is “dry” due to fibrosis)
can also do genetic testing for JAK2, MPL and CALR genes
