Myeloproliferative Disorders Flashcards
ET
Myelofibrosis (tear drop cells, monolobed PMNs)
Two most common leukemias
CLL (most common) and AML
PV (Absence of iron is a typical finding in the marrow at diagnosis. Iron stores have been depleted to sustain the expanded erythrocyte mass.)
CML (many different lineages)
Basophilia is common in which myeloproliferative disorders?
CML, myelofibrosis, PV
Elevated or low in CML:
Uric acid
LAP
B12
Transcobalamine
Uric acid - elevated (tumor lysis syndrome)
LAP - low (myelocytes are non-functional = not producing alk phos)
B12 - elevated
Transcobalamine - elevated (B12 binding protein)
Median duration CML:
Chronic phase
Accelerated phase
Blast phase
Chronic phase - 5-6 years
Accelerated phase - 6-9 mo
Blast phase - 3-6 mo
Who discovered Philadelphia chromosome?
Janet Rowley
What % of patients with CML have t(9:22)?
95%
What % of cells express t(9:22) in person with CML with that cytogenetic abnormality?
100% (of RBC, WBC, monocytes, platelets)
Only cure for CML
HSCT
Why are busulfan and hydroxyurea not that great?
Can’t control CML once it’s in accelerated phase
Targeted tx for CML. MOA?
Imatinib - binds in ATP binding pocket of tyrosine kinase, inhibiting it
How long must patient be on imatinib before almost all peripheral blood is back to normal?
~1 month!!
More efficacious: IFN or imatinib?
Imatinib (much more so)
Resistance to imatinib mediated by what mutation?
T-3151
Pathway beginning with EPO binding EPO-R
Jak-2 activated –> STAT/PI3K/AKT/MAPK –> RBC precursor proliferation and differentiation
Jak-2 inhibitors are effective against which diseases?
PV, ET, myelofibrosis
Jak-2 mutation is most common in which of these: PV, ET, myelofibrosis
PT (90-95%)
Homozygous Jak-2 mutation indicative of:
Pt presents with bone pain, portal HTN, muscle wasting, SOB, palpitations. Lab shows thrombocytosis, leukocytosis.
Myelofibrosis
Two major causes of death for myelofibrosis pts
Vascular disease (~35%), acute leukemia (~25%)
Two causes of secondary thrombocytosis
Refractory thrombocytosis (after BM suppression)
Splenectomy
Least common MPD
ET
Secondary vs ET
2ndary = ELEVATED TPO, no splenomegaly, platelet function and morphology is normal, megs are normal
ET = NORMAL TPO, 40% splenomegaly, megs abnormal
Aortic and mitral valvular leaflet thickening or vegetations
3 risk factors for thrombosis
- Phx
- Advanced age
- CV risk factors (i.e. smoking)
What is Budd-Chiari syndrome and which heme disorder associated with it?
Occlusion of hepatic vein
ET
Why can ET cause spontaneous abortion/premature deliveries/etc
Thrombotic complications causing placental insufficiency
Two Rx specifically mentioned for ET
Hydroxyurea (ribonucleotide reductase inhibitor)
Anagrelide
MOA: Anagrelide
AE?
Inhibits differentiation of megs = fewer platelets
CHF, HA, thrombocytopenia
Altitude sickness
Reactive polycythemia
Causes of reactive polycythemia
**Anything that would increase EPO
Altitude sickness
Atrial septal defect
Renal hypoxia (due to artery ligation, tumor, hydronephrosis)
Tumor (hypernephroma)
Most common symptom of PV
HA
Blurred vision would be most associated with which MPD?
PV (causes distention of retinal vessels)
Elevated or low in PV:
LAP
B12
Iron stores
LAP - high (hyperfunctional cells)
B12 - high
Iron stores - low
Raynaud phenomenon
PV
TOC for PV
Phlebotomy
(myelosuppressive Rx given when platelet/WBC count rises or when pruritic)
Cross country runner presents with headache, bleeding, and cyanosis. Dx?
Reactive polycythemia due to volume depletion
