AM Report

Bridger 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 66
Hemoglobin (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)