1. Polycythemia Vera (lots of red cells - for real)
An uncommon disorder - distinguish from other causes of erythrocytosis
Diagnosis depends on knowledge of erythropoeisis
Complications most commonly from thrombosis and vascular incidents
Long natural history with treatment

2. Definition of Erythrocytosis
Normal hematocrit at FMLH:
Male 47  5 percent
Female 42  5 percent
Normal hemoglobin at FMLH:
Male 15  2 gm/dl
Female 13.5  1.5 gm/dl

3. Absolute vs. Relative Erythrocytosis

4. RBC Mass - 51Chromium Assay

5. Pathophysiology of Polycythemia

6. Secondary Polycythemia
Appropriate EPO (tissue/kidney hypoxia)
pulmonary disease
high altitude
congenital heart disease
abnormal hemoglobin
high affinity
carboxyhemoglobin

7. Secondary Polycythemia
Inappropriate EPO (ectopic production)
Tumors (hepatoma, renal carcinoma, leiomyoma, hamartoma)
Renal disorders (transplantation, cysts)
hemangiomas
Androgen abuse
EPO abuse
Familial polycythemia

8. Polycythemia Vera P. vera is a rare disease Median age 60 - 65 years
Clinical features
Attributed to increased blood viscosity and poor oxygen delivery to organs (brain)
Poor O2 delivery leads to ischemia and thrombosis
Expanded blood volume and viscosity leads to increased cardiac work load

9. Oxygen delivery vs. Hematocrit
J Clin Invest 1963;42:1150

10. P. Vera - Symptoms & Signs
Headache
Weakness
Pruritis (aquagenic)
Dizziness
Diaphoresis
Visual disturbance
Weight loss
Signs
Splenomegaly 70%
Skin plethora 67%
Hepatomegaly 40%
Conjunctival plethora 59%
Systolic Hypertension 72%

11. P. Vera - Diagnosis (PVSG criteria)
RBC mass elevated
SaO2 > 92%
Splenomegaly (or)
thrombocytosis
Leukocytosis
high LAP
high B12
Significance
True vs. spurious
R/O most 2 causes
Evidence for MPD
False Positive 0.5%
smokers, drinkers

12. P. vera - Bone Marrow Biopsy

13. P. Vera - Natural History

14. Treatment - PVSG Founded 1967 Protocol 01 Protocol 05 Protocol 08
Phlebotomy vs. Chlorambucil vs. 32P
Protocol 05
Phlebotomy with ASA, dipyridamole vs. 32P
Protocol 08
Phlebotomy vs. Hydroxyurea

15. Risk of Thrombosis from Treatment (PVSG 01)

16. Types of Thrombosis (PVSG 01)

17. Risk of Cancer from Treatment (PVSG 01)

18. PVSG 08 - Hydroxyurea

19. Treatment Options - Phlebotomy
Advantages
quick, easy
less trips to clinic
low risk of cancer
no medication need
compliance
Disadvantages
thrombosis risk
symptoms of iron deficiency
perhaps faster to “spent phase”
vascular access
cardiovascular effects
no effect on spleen
no effect on platelets

20. Treatment Options - 32P Advantages Disadvantages quick and effective
thrombosis risk low
no medication
follow-up need minimal
compliance easier
reduces spleen size
lowers all counts
few side-effects
Disadvantages
risk of leukemia
uncontrolled effects
childbearing risk
radiation issues

21. Treatment Options - Hydroxyurea
Advantages
quick and effective
thrombosis risk low
reduces spleen size
lowers all counts
leukemia risk low
few side-effects
Disadvantages
close monitoring
childbearing risk
compliance (daily medication)
GI toxicity (rare)
leukemia risk (?)

22. Treatment Options - Summary