AM ReportBridger Clarke

12/10/2007

Presence of a chronic nonreactive thrombocythemic state that is not accounted for by one of the other chronic myeloproliferative disorders [chronic myelogenous leukemia (CML), polycythemia vera (PV), primary myelofibrosis (PMF)].

2.5 new cases/100,000 population per year

Approximately 6,000 people are diagnosed each year in the US.

Female to male ratio of approximately 2:1

Median age at diagnosis is 60 years

Characteristic Percent or median result (range)

Age 49.8 (17-98)Sex, percent female 66Hemoglobin (g/dL) 13.7 (9.1-16.8)

WBC count (x 10(3)/microL) 9.0 (4.1-25.2)

Platelet count (x 10(3)/microL) 1000 (454-3460)

Palpable splenomegaly, percent 34.7

Asymptomatic, percent 45.3

Vasomotor symptoms, percent 13.3

History of fetal loss (women only), percent 11.2

History of thrombosis, percent 21.3

History of hemorrhage, percent 9.3

Normal cytogenetics, percent 87.4

JAK2 mutation, percent 48.7

Up to one-half of patients with ET may be totally asymptomatic at presentation.

The remaining patients may report "vasomotor" symptoms or manifest thrombohemorrhagic complications.

Vasomotor Symptoms:

• Headache • Lightheadedness • Syncope • Atypical chest pain • Acral paresthesia • Livedo reticularis • Erythromelalgia (burning pain of the hands or feet associated

with erythema and warmth)• Transient visual disturbances (eg, amaurosis fugax,

scintillating scotomata, ophthalmic migraine)

Thrombosis and Hemorrhage:

• Stroke, transient ischemic attacks• Retinal artery or venous occlusions• Coronary artery ischemia• Pulmonary embolism• Hepatic or portal vein thrombosis• Deep vein thrombosis• Digital ischemia

Platelet count >600,000/microL Megakaryocytic hyperplasia on bone

marrow aspiration and biopsy

Absence of the Philadelphia chromosome

Absence of infection, inflammation, and other causes for reactive thrombocytosis

Normal red blood cell (RBC) mass or a hemoglobin concentration <13 g/dL

Presence of stainable iron in a bone marrow aspiration or 1 g/dL increase in hemoglobin concentration after a one month trial of oral iron therapy.

Approximately 50 percent of patients with ET have shown presence of the JAK2 V617F mutation

Most patients with ET enjoy a normal life expectancy without associated disease-related complications

Risk factors for inferior survival• Low hemoglobin level (<12 g/dL in females and <13.5 in

males) • Age 60 years • Leukocyte count 15,000/microL • Smoking, diabetes mellitus, prior venous thrombosis

Transformation into polycythemia vera, primary myelofibrosis, or acute myeloid leukemia (AML) occurs on the order of 1-4%

Risk factors for disease transformation• Low hemoglobin level (<12 g/dL in females, <13.5 in

males) • Platelet count 1,000,000/microL • Increased age

Low dose aspirin is the treatment of choice for vasomotor symptoms

Hydroxyurea has been shown to reduce the risk of thrombosis

Maintenance of the platelet count <400,000/microL may be associated with further reduction in thrombotic risk

Impairs DNA repair by inhibiting ribonucleotide reductase

Varying degrees of neutropenia and megaloblastic anemia accompany the platelet-lowering effect of HU

Rising MCV is indicative of appropriate drug action

Inhibits platelet aggregation via platelet anti-cyclic AMP phosphodiesterase activity

Interference with megakaryocyte proliferation and maturation, resulting in platelet underproduction

Toxicity:• Related to the drug's direct vasodilatory and inotropic

effects • headache (34 percent), palpitations/tachycardia (23

percent), fluid retention (14 percent), and diarrhea (8 percent)