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

RBC Mass - 51Chromium Assay

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 J Clin Invest 1963;42:1150

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%

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

P. vera - Bone Marrow Biopsy

P. Vera - Natural History

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

Risk of Thrombosis from Treatment (PVSG 01)

Types of Thrombosis (PVSG 01)

Risk of Cancer from Treatment (PVSG 01)

PVSG 08 - Hydroxyurea

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 - 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

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