Myeloproliferative and Myelodysplastic Syndromes Flashcards
Polycythemia Vera (genetics + symptoms + labs)
- Proliferation of RBCs
- 95-97% have V617F mutation in exon 14 of JAK2 gene
- Symptoms - (related to inc red cell mass) ruddy complexion, splenomegaly, hepatomegaly, conjunctival plethora, engorged optic veins, HTN, cutaneous ulcers, arterial or venous thrombosis
- Labs - inc red cell mass/Hb/HCT, depressed Epo (Epo insensitive), platelets/WBCs may be elevated, elevated LDH and uric acid (from inc cell turnover)
PV versus Secondary Polcythemia
- Secondary Polycythemia (Epo sensitive)
- Appropriate - obesity hypovent, lung disease, sleep apnea, high altitude, cyanotic heart disease
- OR Inappropriate - tumors that cause atopic Epo production or stimulate hematopoiesis directly and endocrine disorders and use of exogenous Epo
PV Dx
- (need all major or no mutation and minor)
- Major -
- Inc Hb or HCT
- JAK2V617F or similar mutation
- BM showing hypercellularity of all myelocytes - Minor -
- Below normal Epo
PV Complications
Myelofibrosis, MDS/AML, hyperviscosity –> thrombosis / hemorrhage
PV Tx
- Phlebotomy to get down to HCT < .45
- Chemical cytoreduction (hydroxyurea or interferon)
- ASA to prevent thrombosis
Essential Thrombocytopenia (genetics + symptoms)
- Proliferation of megakaryocytes
- > 50% have JAK2 mutation
- Majority asymptomatic (normally find high platelet count or thrombotic event w/ few risk factors)
- Headache, visual disturbance, dizziness, syncope, burning eryhtromelagia (episodic blockage of vessels - then red and inflammed when unblocked), thrombosis (arterial > venous), GI bleed, epitaxis, splenomegaly
What is the number 1 concern in ET?
Death due to thrombosis
ET Dx
(need all major or no mutation and minor)
- Major -
- Inc platelets
- BM biopsy shows loose clusters of megakaryocytes w/ staghorn appearance of nuclei w/ inc # nuclei
- JAK2 mutation
- R/o CML/PV/PMF/myelodysplasia - Minor - clonal platelet marker
ET versus Secondary Thrombocytosis
- Acute w/ known drug, infection or blood loss OR known iron def, asplenia, chronic inflammatory disease, hemolytic anemia, cancer
- Important b/C ET has risk of thrombosis while secondary thrombocytosis does NOT
ET Tx
If high risk of thrombosis use platelet lowering agent (destroys platelets - hydroxyura, interferon-alpha, busulfan) or anagrelide (blocks megakaryocyte proliferation) AND aspirin
Primary Myelofibrosis (hallmark/ presentation)
- Hallmark = marrow fibrosis and myeloid metaplasia (AKA extramedullary hematopoiesis)
- Extramedullary hematopoiesis –> splenomegaly, hepatomegaly, LUQ pain, early satiety
- Bone marrow failure –> fatigue, dyspnea, bleeding, bruising
Labs and Smear in PMF
- Labs - anemia, early leukocytosis/ thrombocytosis as extradmedullary takes over but later the extramedullary sites cannot keep up so leukopenia/thrombocytopenia, can transform to AML –> blasts and inc in leukocytosis again, inc uric and LDH from cell turnover
- Smear - Nucleated RBCs and tear drop cells
PMF Dx
(need all 3 major and 2 minor)
- Major
- Megakaryocyte proliferation and gathered in tight clusters w/ atypical cloud-like nuclei
- R/o CML, PV, MDS
- JAK2 mutation or other clonal marker OR no evidence that fibrosis is reactive - Minor
- Leukoerythroblastosis
- Inc LDH
- Anemia
- Palpable spleen
PMF Complications
Morbidity/mortality associated w/ hematopoietic failure, hypersplenism, adv age, evolution to AML
PMF Tx
- Only cure is HSCT (may not be possible in this older population)
- Ruxolitinib -JAK1 and JAK2 inhibitor to dec spleen size and dec symptoms
- Side effects - thrombocytopenia, anemia, fatigue, dyspnea, headache, dizziness, nausea
- Largely supportive care
