13 - Myeloproliferative Disorders Flashcards
4 major myeloproliferative disorders
CML
polycythemia vera
essential thrombocythemia
idiopathic myelofibrosis
are myeloproliferative disorders acquired or congenital?
acquired
JAK2 mutation is associated with
polycythemia vera, essential thrombocythemia, and myelofibrosis
JAK2 mutation causing myeloproliferative disorder via what mechanism?
persistent signaling through spontaneous dimerization in the absence of EPO/TPO
ddx of absolute polycythemia
primary - polycythema vera for example. abnormality in erythroid progenitors, grow w/ little to no EPO
secondary - physiologically appropriate (sleep apnea, high altitude, Hb abnormalities) or inappropriate (tumors making EPO, renal dz/transplant, anabolic steroids, cobalt/nickel exposure)
3 congenital polycythemias
high O2 affinity hb mutation
2,3 bpg deficiency
congenital methemoglobinemias
clinical presentation of absolute polycythemias
HA thrombosis hypermetabolic sx - fevers, night sweats, wt loss pruritis - freq when taking hot bath plethora - redness in face splenomegaly
lab dx of polycythemia vera
low serum EPO levels (not specific) JAK2 mutation (95% sensitive) bone marrow - hypercellular, absence of stainable iron, abnormal karyotype in about 30%
prognosis for polycythemia vera
avg survival 10-12 yrs
conversion to spent phase - myeloid metaplasia
converstion to acute leukemia
thrombosis / bleeding
main morbidity assoc w/ essential thrombocythemia
thrombotic/bleeding events
diagnostic criteria for essential thrombocythemia
platelet count >600k marked megakaryocytic hyperplasia abundant platelet clumps normal red cell mass no Philadelphia chromosomes or myelofibrosis
3 drugs that can be used to treat essential thrombocythemia
hydroxyurea, interferon, anagrelide
features of idiopathic myelofibrosis
marrow activity outside bone marrow in areas not active in post fetal life - not result of being crowded out
increased fibrotic activity and reticulin
sx of idiopathic myelofibrosis
hypermetabolic gout bleeding/thrombosis anemia splenomegaly hepatomegaly
dx of idiopathic myelofibrosis
PBS - tear drop RBCs, nucleated RBCs, immature granulocytes
bone marrow - frequent “dry tap”, biopsy is hypercellular/fibrotic
inc number of circulating CD34 cells