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

 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

Plasma Vol RBC

Normal

Spurious

Polycythemia

RBC Female Male 25 ml/kg

> 32 ml/kg

Plasma 35 ml/kg 33 ml/kg

Total Blood Vol 60 ml/kg 61 ml/kg

28 ml/kg
> 36 ml/kg

 Appropriate

EPO (tissue/kidney hypoxia)

pulmonary disease high altitude congenital heart disease

abnormal hemoglobin high affinity carboxyhemoglobin

 Inappropriate

EPO (ectopic production)

Tumors (hepatoma, renal carcinoma, leiomyoma,

hamartoma) Renal disorders (transplantation, cysts) hemangiomas Androgen abuse EPO abuse Familial polycythemia

 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

180 160

Oxygen Transport

140 120 100 80 60 40 20 0 0 20 40 Hct

J Clin Invest 1963;42:1150

60

80

 Symptoms

Signs

Headache Weakness Pruritis (aquagenic) Dizziness Diaphoresis Visual disturbance

Splenomegaly 70% Skin plethora

Weight loss

67% Hepatomegaly 40% Conjunctival plethora 59% Systolic Hypertension 72%

 Criteria

Significance

RBC mass elevated SaO2 > 92% Splenomegaly (or)

thrombocytosis Leukocytosis high LAP high B12

True vs. spurious R/O most 2 causes Evidence for MPD

False

Positive 0.5%

smokers, drinkers

Thrombosis/embolism AML Other cancer Hemorrhage Myelofibrosis Other

PVSG 31% 19% 15% 6% 4% 25%

GISP 30% 15% 16% 3% 3% 35%

 Founded

1967 Protocol 01
Phlebotomy vs. Chlorambucil vs.
Protocol Protocol
32P

05
32P

Phlebotomy with ASA, dipyridamole vs.

08

Phlebotomy vs. Hydroxyurea

Treatment Phlebotomy Chlorambucil

32

3 years 23% 10% 13%

Overall 38%* 30% 34%

* p = 0.015

Event
CVA Venous MI P. arterial Pulm. Infarct

Percent
35% 26% 12% 9% 6%

Treatment Phlebotomy

7 years 1.29

14 years 1.49 2.38* 1.86*

* p < 0.01

Chlorambucil 2.00*
32

1.88*

Treatment
Hydroxyurea
(n = 51)

Thrombosis
22% 37%

Leukemia
6% 2%

Phlebotomy
(n = 134)

 Advantages

Disadvantages

quick, easy less trips to clinic low risk of cancer no medication need compliance

thrombosis risk symptoms of iron

deficiency perhaps faster to spent phase vascular access cardiovascular effects no effect on spleen no effect on platelets

 Advantages

Disadvantages

quick and effective thrombosis risk low no medication follow-up need minimal compliance easier reduces spleen size

risk of leukemia uncontrolled effects childbearing risk radiation issues

lowers all counts

few side-effects

 Advantages

Disadvantages

quick and effective thrombosis risk low reduces spleen size lowers all counts leukemia risk low few side-effects

close monitoring childbearing risk compliance (daily

medication) GI toxicity (rare) leukemia risk (?)

P. Vera Phlebotomize to HCT < 45

Age > 70 Hydroxyurea 32P?

Age 50 - 70 Hydroxyurea Phlebotomy

Age < 50 Phlebotomy Hydroxyurea