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.
2. BM showing ↑ numbers of enlarged mature megakaryocytes; no left-shift of granulopoiesis or ↑ in erythropoiesis
3. Not meeting WHO criteria for PV, PMF, CML, MDS, or other myeloid neoplasm
4. Acquired Mt of clonal marker or no reactive cause of thrombocytosis
(Adapted from Blood 2011;117:1472)
Genetics
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.
Disease Sequelae
Thrombotic events: Clinical RF for thrombosis not completely understood, but include: Age > 60, h/o thrombosis, WBC > 11 × 109/L, CVRF (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).
↑ w/disease duratrion: 3-10% in first decade after dx. 6-30% in second decade after dx
Low risk
↑ w/disease duration. 1-2.5% in first decade after dx. 5-8% in second decade after dx.
Risk Stratification for Thrombotic Events in Essential Thrombocythemia
Risk Category
Risk Factor(s)
High risk
Age > 60
H/o thrombotic event
Plt count > 1.5 million
Intermediate risk
Age 40-60
Low risk
Age < 40
(Adapted from Blood 2011;117:1472)
Treatment
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;332:1132). 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.
POLYCYTHEMIA VERA
Raajit Rampal
Clonal hematopoietic disorder resulting in ↑ red cell mass
Epidemiology
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), GIsx (↑ prevalence of gastroduodenal lesions & H. pylori positivity), & 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.
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