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
Normal Spurious Polycythemia
Plasma Vol
RBC
RBC Mass -
51
Chromium Assay
RBC Plasma Total
Blood Vol
Female 25 ml/kg
> 32 ml/kg
35 ml/kg 60 ml/kg
Male 28 ml/kg
> 36 ml/kg
33 ml/kg 61 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 O
2
delivery leads to ischemia and thrombosis
Expanded blood volume and viscosity leads to
increased cardiac work load
Oxygen delivery vs. Hematocrit
0
20
40
60
80
100
120
140
160
180
0 20 40 60 80
Hct
O
x
y
g
e
n

T
r
a
n
s
p
o
r
t
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
SaO
2
> 92%
Splenomegaly (or)
thrombocytosis
Leukocytosis
high LAP
high B
12

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
PVSG GISP
Thrombosis/embolism 31% 30%
AML 19% 15%
Other cancer 15% 16%
Hemorrhage 6% 3%
Myelofibrosis 4% 3%
Other 25% 35%
Treatment - PVSG
Founded 1967
Protocol 01
Phlebotomy vs. Chlorambucil vs.
32
P
Protocol 05
Phlebotomy with ASA, dipyridamole vs.
32
P
Protocol 08
Phlebotomy vs. Hydroxyurea
Risk of Thrombosis from Treatment
(PVSG 01)
Treatment 3 years Overall
Phlebotomy 23% 38%*
Chlorambucil 10% 30%
32
P 13% 34%
* 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
P 1.88* 1.86*
* p < 0.01
PVSG 08 - Hydroxyurea
Treatment Thrombosis Leukemia
Hydroxyurea
(n = 51)
22% 6%
Phlebotomy
(n = 134)
37% 2%
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 -
32
P
Advantages
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
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
Age > 70
Hydroxyurea
32P?
Age 50 - 70
Hydroxyurea
Phlebotomy
Age < 50
Phlebotomy
Hydroxyurea
P. Vera
Phlebotomize to HCT < 45