Clonal hematopoietic disorder resulting in ↑ red cell mass
• Incidence: Median age at dx is 60 y. 1/5 of pts under age 40
Signs and Symptoms
• Sx resulting from disease include: Erythema, pain, burning, & occasional cyanosis in hands & feet (erythromelalgia), vasomotor sx (syncope, atypical CP light-headedness), & visual complaints (amaurosis fugax)
• 2° events: Thrombosis, both arterial & venous, may be initial presentation of disease. Hemorrhage, particularly in pts w/plt count >1 million, may be initial manifestation
Exam and Laboratory
• Common physical findings: Organomegaly (splenomegaly) hepatomegaly uncommon.
• Lab findings: Sustained plt count >450000
• Other causes of thrombocytosis must be excluded to make dx.
• Other causes of thrombocytosis: Reactive thrombocytosis (iron deficiency, inflammation, infxn, malignancy), MDS (JAK2V617F positive RARS-T can p/w thrombocytosis), MF, & PV
• WHO diagnostic criteria (Table 1): Dx requires all four criteria. Presence of ↑ reticulin fibrosis excludes dx of ET.
• FHx of thrombocytosis should be assessed for possibility of familial essential thrombocythemia (rare autosomal dominant disorder).
• Mt in JAK-STAT pathway cause disease in majority of cases. JAK2V617F: Found in approx 50% of ET Pts. However, not specific for dx of ET as occurs in other MPNs.
• Mt in exon 10 of MPL (thrombopoietin receptor) found in up to 4% of remaining pts.
• Lower frequency Mt in epigenetic regulator TET2 may contribute to disease but role in pathogenesis unclear.
• Chromosomal alterations such as trisomy 8 or 9, or deletion of chromosome 20q or 13q may occur.
• Thrombotic events: Clinical RF for thrombosis not completely understood, but include: Age > 60, h/o thrombosis, WBC > 11 × 109/L, CV RF (obesity, smoking). Presence of JAK2V617F Mt also a RF.
• Hemorrhagic events: RF include plt count >1 million, or ASA
>325 mg/daily. Pts w/excessive plt count at risk of acquired vWD (check Ristocetin cofactor assay)
• Disease evolution: May evolve to post-ET
MF or AML. RF for POD incomplelety understood. Single center study indicates low Hb (female < 12, male < 13.5), age, plt count > 1 million as factors for leukemic transformation (Leukemia 2007;21:270).
• Cytoreductive Rx: Used to reduce leukocyte count, plt count, spleen size, ameliorate disease-related sx, & to ↓ risk of thrombosis. No clear consensus on when to cytoreduce low-risk pts w/plt count > 1 million.
Hydroxyurea proven to reduce thrombosis risk in ET (NEJM 1995;332:11>32). Titrate dose to clinical response or desired lab parameters. Contraindicated in pregnant pts.
Anagrelide can be used as second-line Rx. Anagrelide plus ASA shown to be inferior to Hydroxyurea plus ASA in preventing thrombosis (NEJM 2005;353:33).
Alpha-Interferon or Pegylated Interferon alpha 2a/2b can also be used in first-line setting (contraindicated in thyroid disorders or h/o depression). Optimal role of JAK inhibitors under investigation.
Busulfan, an alkylating agent, can be used to control plt count in elderly pts, but is a/w ↑ risk of leukemic transformation.
Radioactive phosphorous also can be used in elderly pts, but also a/w ↑ risk of leukemic transformation.
Pipobroman may also be used in elderly, but also a/w ↑ risk of leukemic transformation.
• Antiplatelet Rx: Retrospective data indicate ASA may reduce thrombotic risk in ET. Caution w/plt count >1 million due to bleeding risk: R/o acquired vWD & use doses <100 mg/d.
• Symptomatic control: Erythromelalgia may respond to ASA.
• RF modification: Tobacco cessation, wt loss, may ↓ thrombosis risk in pts w/ET.