Myeloproliferative Disorders

Question 1

What are myeloproliferative disorders

Answer 1

Overproduction of myeloid cells (granulocytes, red cells, platelets)
Leads to increased peripheral cell counts

Question 2

What is the common precursor of all our bloods cells

Answer 2

Multipotential hematopoietic stem cell
(Hemocytoblast)

Question 3

What are the four major types of myeloproliferative disorders

Answer 3

Chronic myeloid leukemia (granulocytosis)
Polycythemia vera (red blood cells, platelets and granulocytes)
Essential thrombocytosis (platelets)
Myelofibrosis (overproduction of fibrous tissue in the bone marrow)

Question 4

What is polycythemia vera

Answer 4

Elevated red blood cell mass due to increased hemoglobin and hematocrit
May also have leukocytosis or thrombocytosis

Question 5

What are the clinical features of polycythemia

Answer 5

Many patients asymptomatic so is detected by routine CBC
Hypertension and flushing of the skin (due to increased RBC mass which leads to increase blood volume)
Thrombosis (increased viscosity of blood, increased platelets, DVT, often Budd Chiari syndrome (hepatic vein)
Splenomegaly
Red puffy skin (facial plethora)
Aquagenic pruritus - often presenting complaint (unbearable pruritus after warm bath or shower)
Erythromelalgia (burning sensation in hands and feet)

Question 6

What are some differentials for polycythemia vera

Answer 6

Hypoxia from lung disease
EPO secreting tumors
Renal cell carcinoma
Hepatocellular carcinoma

Question 7

What mutation is commonly found in polycythemia vera

Answer 7

JAK2 mutation

Question 8

Which myeloproliferative disorders are associated with JAK2 mutation

Answer 8

Polycythemia vera
Essential thrombocytosis
Myelofibrosis

Question 9

Affects gene for enzyme Janus kinase 2
Mutation results in abnormal function/growth of myeloid progenitor cells
Progenitor cells become hypersensitive to cytokines
More growth and longer survival of myeloid precursor cells
What mutation could this be

Answer 9

JAK2 mutation

Question 10

What is the diagnostic criteria for polycythemia vera

Answer 10

Elevated hemoglobin or hematocrit (> 16.5 g/dL or 49% in men and > 16 g/dL or 48% in women)
Bone marrow biopsy that shows hypercellularity (trilineage growth or panmyelosis - which means growth of progenitor cells involving all of the myeloid lineage cells)
Presence of JAK2 mutation
Minor criteria - reduced serum EPO
To make diagnosis you need all the 3 major criteria or first two major plus minor criteria

Question 11

How is polycythemia vera treated

Answer 11

Phlebotomy (goal Hct < 45%)
Low-dose aspirin (for thrombosis prevention)
Hydroxyurea (inhibits ribonucleotide reductase - low DNA, low cell division)
Ruxolitinib (JAK inhibitor, used in refractory cases only)