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Polycythemia Vera(lots of red cells - for real)An uncommon disorder - distinguish from other causes of erythrocytosisDiagnosis depends on knowledge of erythropoeisisComplications most commonly from thrombosis and vascular incidentsLong natural history with treatmentDefinition of ErythrocytosisNormal hematocrit at FMLH:Male 47 5 percentFemale 42 5 percent

Normal hemoglobin at FMLH:Male 15 2 gm/dlFemale 13.5 1.5 gm/dlAbsolute vs. Relative Erythrocytosis

RBC Mass - 51Chromium Assay

Pathophysiology of PolycythemiaSecondary PolycythemiaAppropriate EPO (tissue/kidney hypoxia)pulmonary diseasehigh altitudecongenital heart diseaseabnormal hemoglobin high affinitycarboxyhemoglobinSecondary PolycythemiaInappropriate EPO (ectopic production)Tumors (hepatoma, renal carcinoma, leiomyoma, hamartoma)Renal disorders (transplantation, cysts)hemangiomasAndrogen abuseEPO abuseFamilial polycythemiaPolycythemia VeraP. vera is a rare diseaseMedian age 60 - 65 yearsClinical featuresAttributed to increased blood viscosity and poor oxygen delivery to organs (brain)Poor O2 delivery leads to ischemia and thrombosisExpanded blood volume and viscosity leads to increased cardiac work loadOxygen delivery vs. Hematocrit

J Clin Invest 1963;42:1150P. Vera - Symptoms & SignsSymptomsHeadacheWeaknessPruritis (aquagenic)DizzinessDiaphoresisVisual disturbanceWeight lossSignsSplenomegaly 70%Skin plethora67%Hepatomegaly40%Conjunctival plethora 59%Systolic Hypertension 72%P. Vera - Diagnosis (PVSG criteria)CriteriaRBC mass elevatedSaO2 > 92%Splenomegaly (or)thrombocytosisLeukocytosishigh LAPhigh B12SignificanceTrue vs. spuriousR/O most 2 causesEvidence for MPD

False Positive 0.5%smokers, drinkersP. vera - Bone Marrow Biopsy

P. Vera - Natural History

Treatment - PVSGFounded 1967Protocol 01Phlebotomy vs. Chlorambucil vs. 32PProtocol 05Phlebotomy with ASA, dipyridamole vs. 32PProtocol 08Phlebotomy vs. HydroxyureaRisk of Thrombosis from Treatment(PVSG 01)

* p = 0.015Types of Thrombosis(PVSG 01)

Risk of Cancer from Treatment(PVSG 01)

* p < 0.01PVSG 08 - Hydroxyurea

Treatment Options - PhlebotomyAdvantagesquick, easyless trips to cliniclow risk of cancerno medication needcomplianceDisadvantagesthrombosis risksymptoms of iron deficiencyperhaps faster to spent phasevascular accesscardiovascular effectsno effect on spleenno effect on plateletsTreatment Options - 32PAdvantagesquick and effectivethrombosis risk lowno medicationfollow-up need minimalcompliance easierreduces spleen sizelowers all countsfew side-effectsDisadvantagesrisk of leukemiauncontrolled effectschildbearing riskradiation issuesTreatment Options - HydroxyureaAdvantagesquick and effectivethrombosis risk lowreduces spleen sizelowers all countsleukemia risk lowfew side-effectsDisadvantagesclose monitoringchildbearing riskcompliance (daily medication) GI toxicity (rare)leukemia risk (?)Treatment Options - Summary

Chart1475347336545

RBCPlasma Vol

Sheet1RBCPlasma VolNormal4753Spurious4733Polycythemia6545

Sheet1

RBCPlasma Vol

Sheet2HCTOxygen Transport10252010030135401585015060135701008030

Sheet2

Oxygen TransportHctOxygen Transport

Sheet3

RBCPlasmaTotal Blood Vol

Female25 ml/kg

> 32 ml/kg35 ml/kg60 ml/kg

Male28 ml/kg

> 36 ml/kg33 ml/kg61 ml/kg

Chart22510013515815013510030

Oxygen TransportHctOxygen Transport

Sheet1RBCPlasma VolNormal4753Spurious4733Polycythemia6545

Sheet1

RBCPlasma Vol

Sheet2HCTOxygen Transport10252010030135401585015060135701008030

Sheet2

Oxygen TransportHctOxygen Transport

Sheet3

PVSGGISP

Thrombosis/embolism31%30%

AML19%15%

Other cancer15%16%

Hemorrhage6%3%

Myelofibrosis4%3%

Other25%35%

Treatment3 yearsOverall

Phlebotomy23%38%*

Chlorambucil10%30%

32P 13%34%

EventPercent

CVA35%

Venous26%

MI12%

P. arterial9%

Pulm. Infarct6%

Treatment7 years14 years

Phlebotomy1.291.49

Chlorambucil2.00*2.38*

32P 1.88*1.86*

TreatmentThrombosisLeukemia

Hydroxyurea

(n = 51)22%6%

Phlebotomy

(n = 134)37%2%