HEMATOLOGY - myeloproliferative RBC disorders: polycythemia vera

Question 1

what is polycythemia?

Answer 1

EXCESSIVE red cell production –> increase blood viscosity (thickness) & volume (hypervolemia)

Question 2

what are the types of polycythemia? what is each about?

Answer 2

relative polycythemia: from hemoconcentration
- associated with dehydration –> fluid replacement & treat underlying problem

absolute polycythemia: primary & secondary
- primary = polycythemia vera = slow growing cancer, bone marrow makes too many RBCs
- secondary = physiologic response due to hypoxia that causes erythropoietin secretion – seen w ppl at higher altitudes > 10k ft, smokers w incr CO2, COPD, & heart failure

Question 3

what is the pathophysiology of primary absolute polycythemia (aka polycythemia vera, PV)?

Answer 3

95% of ppl have the mutation of tyrosine kinase, Janus Kinase 2 (JAK2) –> erythropoietin receptor is constantly active no matter the level of erythropoietin –> stimulated bone marrow to produce RBCs–> uncontrolled proliferation of RBCs + increase levels of WBCs & platelets (–> leukocytosis + thrombocytosis)

Question 4

what are the risk factors of PV?

Answer 4

its RARE
- b/w 60-80 yo
- males are 2x more likely to develop PV
- more common in whites of eastern european jewish ancestry

Question 5

what are the clinical manifestations of PV?

Answer 5

• aquagenic pruritus: intense & painful itching with heat
• hypervolemia & hyperviscosity –> hypertension –> red color of face, hands, feet, ears & mucus membranes
• headache
• drowsy
• delirium
• mania
• psychotic depression
• chorea
• visual disturbances
• enlarged spleen –> abdominal pain & discomfort

Question 6

what lab data do we use to determine if someone has PV? what are the normal ranges for WBC & plates?

Answer 6

major diagnostic criteria
- high hgb
- high hct
- high RBC mass

erythrocytes appear normal BUT anisocytosis (variation of sizes of RBCs is high) present

moderate increase in WBC & plates
- norm WBC = 5k-10k / uL
- norm plate = 150k-400k / uL

Question 7

what are the diagnostic procedures to determine if someone has polycythemia vera?

Answer 7

bone marrow biopsy with cytogenetic & molecular studies for mutations in JAK2
- presence of a JAK2 mutation = confirming diagnosis of PV

Question 8

what is the disease trajectory of polycythemia vera?

Answer 8

survival of 10-15 years

without treatment –> 50% will die within 18 months bc of thrombosis or hemorrhage
- in a hypercoagulable state –> clogging + occlusion of blood vessels
- tissue ischemia & tissue death (infarction) – stroke
- hemorrhage: bc of inadequate plate function

risk of acute myeloid leukemia (AML, another cancer)

Question 9

how do we treat PV?

Answer 9

goals =
- reduce RBC proliferation & BV
- control symptoms
- prevent clogging & clotting of blood vessels

Question 10

how do we treat low risk patients?

Answer 10

phlebotomy of removing 300-500 mL at a time –> decreases erythrocytes & BV
- every few days until hct reaches acceptable level
- cont PRN q2-3 months

lose-dose aspirin to prevent clotting

Question 11

what medication can we use to treat polycythemia vera? what does it do?

Answer 11

MYELOSUPPRESSANTS –>
- for high risk pts
- slows the production of myeloid cells in bone marrow

Question 12

what drugs are meylosuppressants? what does each one do?

Answer 12

HYDROXYUREA: most common, lower risk for leukemia & thrombosis

INTERFERON (IFN) ALPHA: used when other forms of treatment have failed

Question 13

what is one more thing we can do to decrease RBC? side effects?

Answer 13

radiation therapy with RADIOACTIVE PHOSPHORUS (32P) – slows RBC production
- effects last up to 18 months
- side effects: anemia, leukopenia, thrombocytopenia
- higher risk of acute leukemia