13 - Myeloproliferative Disorders

Question 1

4 major myeloproliferative disorders

Answer 1

CML
polycythemia vera
essential thrombocythemia
idiopathic myelofibrosis

Question 2

are myeloproliferative disorders acquired or congenital?

Answer 2

acquired

Question 3

JAK2 mutation is associated with

Answer 3

polycythemia vera, essential thrombocythemia, and myelofibrosis

Question 4

JAK2 mutation causing myeloproliferative disorder via what mechanism?

Answer 4

persistent signaling through spontaneous dimerization in the absence of EPO/TPO

Question 5

ddx of absolute polycythemia

Answer 5

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)

Question 6

3 congenital polycythemias

Answer 6

high O2 affinity hb mutation
2,3 bpg deficiency
congenital methemoglobinemias

Question 7

clinical presentation of absolute polycythemias

Answer 7

HA
thrombosis
hypermetabolic sx - fevers, night sweats, wt loss
pruritis - freq when taking hot bath
plethora - redness in face
splenomegaly

Question 8

lab dx of polycythemia vera

Answer 8

low serum EPO levels (not specific)
JAK2 mutation (95% sensitive)
bone marrow - hypercellular, absence of stainable iron, abnormal karyotype in about 30%

Question 9

prognosis for polycythemia vera

Answer 9

avg survival 10-12 yrs
conversion to spent phase - myeloid metaplasia
converstion to acute leukemia
thrombosis / bleeding

Question 10

main morbidity assoc w/ essential thrombocythemia

Answer 10

thrombotic/bleeding events

Question 11

diagnostic criteria for essential thrombocythemia

Answer 11

platelet count >600k
marked megakaryocytic hyperplasia
abundant platelet clumps
normal red cell mass
no Philadelphia chromosomes or myelofibrosis

Question 12

3 drugs that can be used to treat essential thrombocythemia

Answer 12

hydroxyurea, interferon, anagrelide

Question 13

features of idiopathic myelofibrosis

Answer 13

marrow activity outside bone marrow in areas not active in post fetal life - not result of being crowded out
increased fibrotic activity and reticulin

Question 14

sx of idiopathic myelofibrosis

Answer 14

hypermetabolic
gout
bleeding/thrombosis
anemia
splenomegaly
hepatomegaly

Question 15

dx of idiopathic myelofibrosis

Answer 15

PBS - tear drop RBCs, nucleated RBCs, immature granulocytes
bone marrow - frequent “dry tap”, biopsy is hypercellular/fibrotic
inc number of circulating CD34 cells

Question 16

tx of idiopathic myelofibrosis

Answer 16

stimulators of erythropoiesis, cytotoxic agents (hydroxyurea), splenectomy all options, but have their downsides
thalidomide or revlimid, stem cell transplant

Question 17

prognosis of idiopathic myelofibrosis

Answer 17

avg survival 4-5 yrs

common causes of morbidity/mortality include anemia, splenomegaly, acute leukemia, infections/bleeding/thrombosis

Question 18

sx of CML

Answer 18

gout
splenomegaly
anemia
bleeding
bone pain

Question 19

findings in CML

Answer 19

all stages of granulocyte maturation in PBS
may have elevated platelets
bone marrow hypercellular w/ elevated M:E ratio
Philadelphia chromosome present
dec LAP (leukocyte alkaline phosphatase) score

Question 20

Philadelphia chromosome assoc w/

Answer 20

CML