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
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
Absolute vs. Relative Erythrocytosis
Plasma Vol
RBC
Normal
Spurious
Polycythemia
RBC Mass -
Female
51Chromium Assay
RBC
Plasma
Total
Blood Vol
25 ml/kg
35 ml/kg
60 ml/kg
33 ml/kg
61 ml/kg
> 32 ml/kg
Male
28 ml/kg
> 36 ml/kg
Pathophysiology of Polycythemia
Secondary Polycythemia
• Appropriate EPO (tissue/kidney hypoxia)
–
–
–
–
pulmonary disease
high altitude
congenital heart disease
abnormal hemoglobin
• high affinity
• carboxyhemoglobin
Secondary Polycythemia
• Inappropriate EPO (ectopic production)
– Tumors (hepatoma, renal carcinoma, leiomyoma,
hamartoma)
– Renal disorders (transplantation, cysts)
– hemangiomas
– Androgen abuse
– EPO abuse
– Familial polycythemia
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
Oxygen delivery vs. Hematocrit
180
Oxygen Transport
160
140
120
100
80
60
40
20
0
0
20
40
60
80
Hct
J Clin Invest 1963;42:1150
P. Vera - Symptoms & Signs
• Symptoms
–
–
–
–
–
–
–
Headache
Weakness
Pruritis (aquagenic)
Dizziness
Diaphoresis
Visual disturbance
Weight loss
• Signs
–
–
–
–
–
Splenomegaly 70%
Skin plethora 67%
Hepatomegaly 40%
Conjunctival plethora 59%
Systolic Hypertension 72%
P. Vera - Diagnosis
(PVSG criteria)
• 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
P. vera - Bone Marrow Biopsy
P. Vera - Natural History
Thrombosis/embolism
AML
Other cancer
Hemorrhage
Myelofibrosis
Other
PVSG
31%
19%
15%
6%
4%
25%
GISP
30%
15%
16%
3%
3%
35%
Treatment - PVSG
• Founded 1967
• Protocol 01
– Phlebotomy vs. Chlorambucil vs. 32P
• Protocol 05
– Phlebotomy with ASA, dipyridamole vs. 32P
• Protocol 08
– Phlebotomy vs. Hydroxyurea
Risk of Thrombosis from Treatment
(PVSG 01)
Treatment
3 years
Overall
Phlebotomy
23%
38%*
Chlorambucil
10%
30%
32
13%
34%
P
* p = 0.015
Types of Thrombosis
(PVSG 01)
Event
Percent
CVA
35%
Venous
26%
MI
12%
P. arterial
9%
Pulm. Infarct
6%
Risk of Cancer from Treatment
(PVSG 01)
Treatment
7 years
14 years
Phlebotomy
1.29
1.49
Chlorambucil 2.00*
2.38*
32
1.86*
P
1.88*
* p < 0.01
PVSG 08 - Hydroxyurea
Treatment
Hydroxyurea
Thrombosis
Leukemia
22%
6%
37%
2%
(n = 51)
Phlebotomy
(n = 134)
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
Treatment Options • Advantages
–
–
–
–
–
–
–
–
quick and effective
thrombosis risk low
no medication
follow-up need minimal
compliance easier
reduces spleen size
lowers all counts
few side-effects
32P
• Disadvantages
–
–
–
–
risk of leukemia
uncontrolled effects
childbearing risk
radiation issues
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 (?)
Treatment Options - Summary
P. Vera
Phlebotomize to HCT < 45
Age > 70
Hydroxyurea
32P?
Age 50 - 70
Hydroxyurea
Phlebotomy
Age < 50
Phlebotomy
Hydroxyurea