Myeloproliferative Neoplasms (MPN)

Question 1

Essential Thrombocythemia pathophysiology

Answer 1

Non-reactive process within the marrow in which there is hyperproliferation of platelets&raquo_space; thrombotic and hemorrhagic complications

BCR-ABL negative

Question 2

Essential Thrombocythemia clinical presentation

Answer 2

Microcirculatory symptoms
Migraines 
Parathesis
Thrombosis 
Hemorrhage

Question 3

Essential Thrombocythemia diagnostic criteria

Answer 3

All 4 major criteria or first 3 major criteria + minor criteria
Major:
1. platelets > 450K
2. Bone marrow w/ large & mature megakaryocytic proliferation
3. Do not meet criteria for other MPNs
4. JAK2, CALR or MPL mutation
Minor:
1.Presences of a clonal marker or no evidence of reactive thrombosis

Question 4

Essential Thrombocythemia treatments

Answer 4

Low dose aspirin&raquo_space; everyone unless contraindicated

Cytoreductive therapy if age > 60 or hx of VTE/bleeding event&raquo_space; Hydroxyurea, Interferon alfa, JAK inhibitors, phosphorus

Question 5

Polycythemia Vera pathophysiology

Answer 5

Acquired or inherited mutation (usually JAK2 mutation) leading to abnormalities within RBC stem cells

Hyperproliferation of all 3 cell lines, with the primary distinguishing feature being erythrocytosis

BCR-ABL negative

Question 6

Polycythemia Vera clinical presentation

Answer 6

Asymptomatic with abnormal lab findings
New onset hypertension
Common symptoms&raquo_space; HA, facial flushing, aquagenic pruritic, night sweats, fatigue
Thrombosis&raquo_space; stroke, MI, splanchnic vein thrombosis

Question 7

Polycythemia Vera diagnostic criteria

Answer 7

All 3 major criteria or first 2 major + 1 minor criteria
Major:
1.Hgb >16.5 or Hct >49% in men/Hgb >16 or Hct >48% in women or increased red cell mass
2. Bone marrow with age-adjusted hypercellularity and trilineage myeloproliferation with pleomorphic/mature megakaryocytes
3. Presence of JAK2 mutation
Minor:
1. Subnormal EPO level

Question 8

Polycythemia Vera treatment

Answer 8

Hematocrit >45% consider phlebotomy, cytoreductive therapy

Aspirin or anti-coag medication if prior thrombosis

Question 9

Primary Myelofibrosis pathophysiology

Answer 9

Chronic neoplasm marked by progressive bone marrow fibrosis, ineffective erythropoiesis, excessive production of dysplastic megakaryocytes, extramedullary hematopoiesis, systemic inflammation, excessive proinflammatory cytokines and shortened survival

BCR-ABL negative

Question 10

Primary Myelofibrosis clinical presentation

Answer 10

Palpable splenomegaly
Abdominal pain 
Cachexia >> wasting 
Early satiety
Bone pain 
Night sweats
Pruritis
Dyspnea
Insomnia
Fatigue

Question 11

Primary Myelofibrosis diagnostic criteria

Answer 11

All 3 major criteria and at least 1 minor criteria
Major:
1. Megakaryocyte proliferative and atypia with either reticulin and/or collagen fibrosis
2. does not meet criteria for other MPN
3. Presence of JAK2, CALR, or MPL mutation or absence of clonal marker or no evidence of reactive bone marrow fibrosis
Minor:
1. Anemia
2. Palpable spleen
3. Leukocytosis&raquo_space; WBC > 11 x 10 9
4. Elevated LDH
5. Leukoerythroblastosis

BM biopsy is crucial for diagnosis

Question 12

Primary Myelofibrosis treatment goals

Answer 12

Splenomegaly reduction
Alleviation of symptoms Improved survival
Fewer disease related complications