PolisitemiPolisitemiaa

dr Putra Hendra SpPDdr Putra Hendra SpPDUNIBAUNIBA

ErythrocytosisErythrocytosis• DefinitionDefinition: An increase in the : An increase in the

number of circulating RBCs number of circulating RBCs per volume of blood. per volume of blood.

• Synonym = Synonym = polycythemiapolycythemia. . • Reflected as an elevated Reflected as an elevated

hemoglobin and hematocrit.hemoglobin and hematocrit.• Causes are classified as:Causes are classified as:

– Secondary (Polyclonal)Secondary (Polyclonal)– Primary (clonal)Primary (clonal)

Secondary Causes of Secondary Causes of Increased Red Cell Mass Increased Red Cell Mass

(Erythrocytosis) (Erythrocytosis) – Chronic pulmonary or cardiac disease Chronic pulmonary or cardiac disease – Decreased 2,3-diphosphoglycerate Decreased 2,3-diphosphoglycerate – High oxygen affinity High oxygen affinity

hemoglobinopathy hemoglobinopathy – Increased carboxyhemoglobin (in Increased carboxyhemoglobin (in

smokers) and methemoglobin smokers) and methemoglobin – Residence at high altitude Residence at high altitude – Adrenal cortical hypersecretion Adrenal cortical hypersecretion – Hydronephrosis Hydronephrosis – Tumors producing erythropoietin or Tumors producing erythropoietin or

anabolic steroids anabolic steroids – Relative (stress) Relative (stress) – Disorders associated with decreased Disorders associated with decreased

plasma volume (e.g., diarrhea, plasma volume (e.g., diarrhea, emesis, renal diseases) emesis, renal diseases)

Diagnosis: Diagnosis: Other Signs and Other Signs and

Symptoms of Polycythemia VeraSymptoms of Polycythemia Vera • More Common More Common • Hematocrit level Hematocrit level

>52 percent (0.52) >52 percent (0.52) in white men, >47 in white men, >47 percent (0.47) in percent (0.47) in blacks and women blacks and women

• Hemoglobin level Hemoglobin level >18 g per dL (180 g >18 g per dL (180 g per L) in white men, per L) in white men, >16 g per dL (160 g >16 g per dL (160 g per L) in blacks and per L) in blacks and women) women)

• Plethora Plethora • Pruritus after Pruritus after

bathing bathing • Splenomegaly Splenomegaly • Weight loss Weight loss • Weakness Weakness • Sweating Sweating

• Less Common Less Common • Bruising/epistaxis Bruising/epistaxis • Budd-Chiari Budd-Chiari

syndrome syndrome • Erythromelalgia Erythromelalgia • Gout Gout • Hemorrhagic events Hemorrhagic events • Hepatomegaly Hepatomegaly • Ischemic digits Ischemic digits • Thrombotic events Thrombotic events • Transient Transient

neurologic neurologic complaints complaints (headache, tinnitus, (headache, tinnitus, dizziness, blurred dizziness, blurred vision, vision, paresthesias) paresthesias)

• Atypical chest pain Atypical chest pain

DiagnosisDiagnosis

• PV should be suspected when PV should be suspected when hemoglobin and/or hematocrit hemoglobin and/or hematocrit levels are elevatedlevels are elevated– (> than 18 g per dL [180 g per (> than 18 g per dL [180 g per

L] in white men and > than 16 g L] in white men and > than 16 g per dL [160 g per L] in blacks per dL [160 g per L] in blacks and women)and women)

• hematocrit level greater than hematocrit level greater than 52 percent (0.52) in white 52 percent (0.52) in white men and 47 percent (0.47) in men and 47 percent (0.47) in blacks and women blacks and women

• A diagnosis of polycythemia vera is made when a A diagnosis of polycythemia vera is made when a patent fulfillspatent fulfills– all three of the major criteriaall three of the major criteria

• OrOr– any two major and any two minor criteriaany two major and any two minor criteria

• Major Criteria Major Criteria – total RBC vol total RBC vol

• Men > or = to 36 mL/kgMen > or = to 36 mL/kg• Women > or = to 32 mL/kgWomen > or = to 32 mL/kg

– arterial 02 saturation > or = to 92% arterial 02 saturation > or = to 92% – Splenomegaly Splenomegaly

• Minor Criteria Minor Criteria – Thrombocytosis with platelet count > Thrombocytosis with platelet count >

400,000/mL 400,000/mL – Leukocytosis with WBC > 12,000/mL Leukocytosis with WBC > 12,000/mL – Increased leukocyte alkaline phosphatase LAP > Increased leukocyte alkaline phosphatase LAP >

100U/L (no infection) 100U/L (no infection) – Serum B12 > 900 pg/mL or binding capacity Serum B12 > 900 pg/mL or binding capacity

UB12 BC > 2200 pg/mL UB12 BC > 2200 pg/mL

P vera - symptomsP vera - symptoms

• Sx common to all erythrocytosisSx common to all erythrocytosis– Headache, Headache, mental acuity, weaknessmental acuity, weakness

• Sx more specific to P vera Sx more specific to P vera – Pruritis Pruritis after bathingafter bathing– ErythromelalgiaErythromelalgia– Hypermetabolic symptomsHypermetabolic symptoms– ThrombosisThrombosis (arterial or venous) (arterial or venous)– HemorrhageHemorrhage

P vera - PEx FindingsP vera - PEx Findings

• Facial plethoraFacial plethora• Splenomegaly Splenomegaly

– found in 70% of ptsfound in 70% of pts

• HepatomegalyHepatomegaly– 40% of pts40% of pts

• Distension of retinal veinsDistension of retinal veins

P vera - Lab FindingsP vera - Lab Findings• CBCCBC

Hgb/HctHgb/Hct WBC in 45%WBC in 45% Plts in 65%Plts in 65%– BasophiliaBasophilia (seen in all MPDs) (seen in all MPDs)

Uric acid (can lead to gout) and Uric acid (can lead to gout) and B12B12

Leukocyte alkaline phosphatase Leukocyte alkaline phosphatase scorescore

• Low epo levelsLow epo levels• Positive JAK2 V617FPositive JAK2 V617F

• Bone marrow studies are not Bone marrow studies are not necessary to establish the necessary to establish the diagnosis but the findings of:diagnosis but the findings of:– hypercellularityhypercellularity– hyperplasia of the erythroid, hyperplasia of the erythroid,

granulocytic and granulocytic and megakaryocytic cell linesmegakaryocytic cell lines

– myelofibrosis myelofibrosis

• support the diagnosis of a support the diagnosis of a myeloproliferative process. myeloproliferative process.

LabsLabs

• Examples of thrombotic Examples of thrombotic events include arterial and events include arterial and venous thrombosis, venous thrombosis, cerebrovascular accident, cerebrovascular accident, deep venous thrombosis, deep venous thrombosis, myocardial infarction, myocardial infarction, peripheral arterial occlusion, peripheral arterial occlusion, and pulmonary infarctand pulmonary infarct

KomplikasiKomplikasi

P vera - TreatmentP vera - Treatment

• PhlebotomyPhlebotomy• Myelosuppressive agentsMyelosuppressive agents

– HydroxyureaHydroxyurea– Alkylating agents such as Alkylating agents such as

busulfanbusulfan– 3232PP

• Interferon alphaInterferon alpha

P vera - phlebotomyP vera - phlebotomy• Generally, the best initial Generally, the best initial

treatment for P veratreatment for P vera– No increase in progression to AMLNo increase in progression to AML– Rapid onsetRapid onset– No BM suppressionNo BM suppression

• Remove 500 cc blood 1-2x/wk to Remove 500 cc blood 1-2x/wk to target Hct 45%, then maintaintarget Hct 45%, then maintain

P vera - P vera - MyelosuppressionMyelosuppression

• Hydroxyurea Hydroxyurea – can be used in conjunction with can be used in conjunction with

phlebotomyphlebotomy– May increase the risk of leukemic May increase the risk of leukemic

transformation from 1-2% to 4-5%transformation from 1-2% to 4-5%

• 3232PP– increase the risk of leukemic increase the risk of leukemic

transformation from 1-2% to 11%transformation from 1-2% to 11%– May be appropriate for pts intolerant May be appropriate for pts intolerant

of medications or for elderly patientsof medications or for elderly patients– Single injection may control Single injection may control

hemoglobin and platelet count for a hemoglobin and platelet count for a year or more.year or more.

P vera - interferon alphaP vera - interferon alpha• BenefitsBenefits

– No myelosuppressionNo myelosuppression– No increase in progression to No increase in progression to

AMLAML– No increase in thrombosis riskNo increase in thrombosis risk– OK in pregnancyOK in pregnancy

• DrawbacksDrawbacks– Must be given by injectionMust be given by injection– Side effects may be intolerable Side effects may be intolerable

in many pts, include flu-like in many pts, include flu-like symptoms, fatigue, fever, symptoms, fatigue, fever, myalgias, malaisemyalgias, malaise

TreatmentTreatment

• Occasionally, chemotherapy Occasionally, chemotherapy may be given to suppress the may be given to suppress the bone marrow.bone marrow.

• The use of anti-platelet The use of anti-platelet therapy (such as aspirin) is therapy (such as aspirin) is controversial because it may controversial because it may cause gastric bleeding.cause gastric bleeding.

• Allopurinol is given for Allopurinol is given for hyperuricemia (gout).hyperuricemia (gout).

Risk stratification in PCVRisk stratification in PCVRisk categoryRisk category Age > 65 or Age > 65 or

h/o h/o thrombosisthrombosis

Cardiovascular risk Cardiovascular risk factors ?factors ?

(high cholesterol, DM, (high cholesterol, DM, smoking, HTN, CHF)smoking, HTN, CHF)

Recommended treatmentRecommended treatment

LowLow NoNo NoNo Phlebotomy and low dose Phlebotomy and low dose ASAASA

IntermediateIntermediate NoNo YesYes Hydrea, phlebotomy and Hydrea, phlebotomy and ASAASA

HighHigh YesYes Hydrea, phlebotomy and Hydrea, phlebotomy and ASAASA

Consider IFNa in pregnant women and busulfan or 32P in elderlyConsider IFNa in pregnant women and busulfan or 32P in elderly

TreatmentTreatment

• splenectomy in patients with splenectomy in patients with painful splenomegaly or painful splenomegaly or repeated episodes of repeated episodes of thrombosis causing splenic thrombosis causing splenic infarction infarction

• The major causes of The major causes of morbidity and mortality are morbidity and mortality are as follows:as follows:– ThrombosisThrombosis– Hemorrhagic complicationsHemorrhagic complications– Peptic ulcer diseasePeptic ulcer disease– Myelofibrosis and pancytopeniaMyelofibrosis and pancytopenia– Acute leukemia or a Acute leukemia or a

myelodysplastic syndrome myelodysplastic syndrome

PrognosisPrognosis