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Polycythemia Vera
Jeff Singerman
December 19, 2006
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Classification
One of the chronic myeloproliferativedisorders
Includes PV, ET, MMM, and CML PV- clonal erthyrocytosis
MMM- marrow fibrosis
ET- clonal thrombocytosis withouterythrocytosis or marrow
fibrosis
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Epidemiology
Incidence- 2/100,000 cases per year,increased in Jewish
populations
Median age of onset- 60 (although canoccur at any age)
Slightly higher incidence in males vs.female (1.2:1)
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Presentation
Non-specific symptoms most common
HA, weakness, dizziness, excess sweating
Pruritis
aquagenic pruritis Mechanism poorly understood
GI complaints- epigastric pain, ulceration orerosions
Erythromelalgia- acral dysesthesia anderythema
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Erythromelalgia
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Bleeding
Spontaneous bleeding at superficialsites and mucous
membranes
Risk is increased by extremeelevations thrombocytosis
Risk also increased by use of
antiplatelet agents
Mechanism not fully elucidated
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Thrombosis
May involve venous, arterial, ormicrovascular circulation
Venous: PE, DVT, Budd-Chiari, PVT, MVT, SVT
Arterial: CVA, ACS
Microcirculation: Erythromelalgia, transientneuro dysfunction,
transient visual disturbances
Mechanism is multifactorial Increased blood viscocity
Displacement of platelets along the vessel wall
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Physical Exam
Splenomegaly
Facial plethora
Hepatomegaly
Conjunctival injection
Excoriation of skin (suggests pruritis)
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Laboratory Findings
Elevated Hcrt (>52 in males, >48 in females)
Does not need to be present for dx
Increased Red Cell Mass (RCM) Do not need to check if Hcrt
>60 in males, >56 in females
Platelets > 400,000 (60% of patients)
WBC > 12,000 (40% of patients) Neutrophil predominance
Elevated LAP score
Elevated B12 or unbound serum B12 bindingcapacity
Low or normal EPO levels
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Bone Marrow Biopsy
Hypercellular with increased megakaryocytes,
giantmegakaryocytes, and decreased marrow iron stores
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Genetics
JAK2 V617F mutation is associated with allCMPDs (except CML)
Present in up to 97% of PV patients
Janus kinase/signal trasducers and activators oftrascription
(JAK/STAT) pathway plays a centralrole in initiating signal
transduction fromhematopoietic growth factor receptors
V617F mutation releases the autoinhibitoryaction of the JAK2
domain and results inincreased expression
Even in the absence of growth factor, JAK2V617F continues to
signal transcription ofhematopoietic precursors.
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JAK/STAT Pathway
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Diagnosis
Polycythemia Vera Study Group (1975) Major Criteria
Increased Red Cell Mass (>36 males, >32 females)
Arterial oxygen saturation > 92%
Splenomegaly
Minor Criteria Platelets > 400,000
WBC > 12,000 LAP score > 100
Serum B12 > 900 or serum unbound B12 bindingcapacity
>2200
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Diagnosis
WHO Criteria: Increased RCM and absence of disorders causing
secondary erythrocytosis AND
Splenomegaly OR clonal genetic abnormalityother than BCR-ABL OR
sponaneous EEC OR twoor more of the following: Platelets >
400,000
WBC > 12,000 Low serum EPO levels
Bone marrow showing panmyelosis wih prominenterythroid and
megakaryocytic proliferation
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Diagnosis
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Prognosis
Untreated: 6 - 18 months
Treated: 9 years
Worsened Prognosis:
Thrombosis
Heme Complications
Transformation into myelofibrosis withmyeloid metaplasia
(MMM)
Evolution into AML/MDS
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Treatment
Phlebotomy
Low-Dose ASA
Reduces risk of thrombosis
Cytoreductive Agents
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Cytoreductive Agents
Hydroxyurea- inhibits DNA synthesis
Leukemogenic?
IFN-- Inhibits stem cell proliferation
Anagrelide- platelet function inhibitorand thrombocytopenic
agent
Busulphan- leukemogenic
Radiotherapy- leukemogenic
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Treatment
Recommendations From the British Committee for Standards in
Haematology
Phlebotomy to maintain Hcrt < 45 Low Dose ASA unless
contraindicated
Cytoreduction considered if: Poor tolerance to phlebotomy
Symptomatic or progressive splenomegaly
Other evidence of disease progression (weightloss, night
sweats)
Thrombocytosis
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Treatment
Recommendations Choice of Cytoreductive Agent:
Less than 40 years old:
1st line: IFN 2nd line: Hydroxyurea or Anagrelide
Age 40 - 75:
1st line: Hydroxyurea
2nd line: IFN or Anagrelide
Greater than 75 years old:
1st line: Hydroxyurea
2nd Line: Radiotherapy or Busulphan
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References
McMullin, MF et al. Guidelines for the diagnosis,
investivation,and management of polycythaemia/erythrocytosis.
BritishJournal of Haematology. 2005; 130: 174-195.
Schafer, AI. Molecular basis of the diagnosis and treatment
of
polycythemia vera and essential thrombocythemia. Blood.2006;
107: 4214-4222.
Tefferi, A. Polycythemia vera: a comprehensive review
andclinical recommendations. Mayo Clinic Procedings. 2003;
78:174-194.
Tefferi, A. Prognosis and treatment of polycythemia vera, UpTo
Date.
Tefferi, A. Diagnostic approach to the patient with
suspectedpolycythemia vera, Up To Date.
