Clonal hematopoietic disorder resulting in ↑ red cell mass
• Incidence: Median age at dx is 60 y. 1/3 of pts under age 50
• Survival depends on age, leukocyte count, & h/o thrombosis
Signs and Symptoms
• Sx resulting from disease include: Pruritus, typically following shower or bath. Erythema, pain, burning, & occasional cyanosis in hands & feet (erythromelalgia), GI sx (↑ prevalence of gastroduodenal lesions & H. pyloripositivity), & visual complaints (amaurosis fugax)
• 2° events: Thrombosis, both arterial & venous, may be initial presentation of disease. Can include mesenteric, portal, & splenic vein thrombosis. Budd–Chiari syndrome may be initial presentation & should prompt consideration of MPN, particularly in younger pt. Gouty Arthritis may also occur.
Exam and Laboratory
• Common physical findings: Organomegaly (splenomegaly, hepatomegaly), evidence of previous thromboses, arthritis, gouty tophi.
• Lab findings: Elevated Hb/Hct, WBC (variable), & Plt count (may cause confusion w/ET; may also reflect depleted iron stores seen in many pts)
• Reactive polycythemia should be excluded. Reactive polycythemia may be 2° to: Smoking, erythropoietin-producing tumors, renal or lung disease, sleep apnea exogenous administration of Epo
• WHO diagnostic criteria (Table 1): Dx requires both major criteria & 1 minor criteria, or first major criteria & 2 minor criteria
• FHxh/o erythrocytosis should be assessed. May reflect 1° familial & congenital polycythemia (autosomal dominant disease a/w low Epo level), or diseases involving congenital cyanotic heart or lung disease, disorders or Hb oxygen affinity, or methemoglobinemia.
• Mt in JAK-STAT pathway cause disease in majority of cases. JAK2V617F: Found in 95% of PV pts. However, not specific for dx of PV as occurs in other MPNs. JAK2 Exon 12 Mt: Found in 4% of remaining pts.
• Mt of negative regulators of JAK: LNK, SOCS. Occur in small minority of pts.
• Lower frequency Mt in epigenetic regulators EZH2, TET may contribute to disease but role in pathogenesis unclear. Often co-occur w/JAK Mt
• Chromosomal alterations may occur in up to half of pts. Deletion of chromosome 20q is most common
• Thrombotic events: Most common clinical consequence of PV. RFs for thrombosis not completely understood, but include: Age, h/o thrombosis, WBC > 15 × 109/L, smoking (Blood 2007;109:1)
• Disease evolution: May evolve to post-PV MF (spent phase or postpolycythemic phase), MDS, or AML. RFs for POD incompletely understood. WBC > 15 × 109/L, JAK2V617F allele burden > 50%, & presence of BM fibrosis are RFs for progression.
• Phlebotomy: Keeping Hct below 45% reduces thrombosis risk (NEJM 2013;368:22)
• Cytoreductive Rx: Used to reduce leukocyte count, plt count, spleen size, ameliorate disease-related sx, & to ↓ risk of thrombosis.
Hydroxyurea is initial Rx. Titrate dose to clinical response or desired lab parameters. Contraindicated in pregnant pts.
Interferon can also be used in first-line setting (contraindicated in thyroid disorders or h/o depression).
Older pts resistant to hydroxyurea can be treated w/pipobroman or busulfan.
32Phosphorus may also be used in elderly pts. Not for use in younger pts due to concern for leukemogenicity.
Role of JAK inhibitors in PV currently under investigation.
• Antiplatelet Rx: Use of low-dose ASA (100 mg/d) demonstrated to reduce risk of MI, stroke, PE, venous thrombosis vs. placebo in PV pts, & should be initiated unless contraindicated (NEJM 2004;350:114)
• Symptomatic control: Sx such as Erythromelalgia may respond to ASA. Pruritus may respond to photochemotherapy (psoralen & ultraviolet A light), Interferon, or Ruxolitinib.
• RF modification: Tobacco cessation. Role of modification of other CV RFs in PV unknown.