WORKUP	Section 5 of 11
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Lab Studies:

• CBC count

• This panel is essential for ET diagnosis.

• The hallmark of ET is a sustained, unexplained thrombocytosis.

• Leukocytosis, erythrocytosis, and mild anemia may be found.

• The peripheral blood may show occasional immature precursor cells (eg, myelocytes, metamyelocytes). Large platelets (thrombocytes) are typically identifiable on routine peripheral blood smear.

• Mild basophilia and eosinophilia may be found.

• Bone marrow

• Approximately 90% of patients show an increase in bone marrow cellularity.

• Megakaryocytic hyperplasia is common.

• Giant megakaryocytes are often observed. Clusters of megakaryocytes may be present; significant dysplasia of the megakaryocytes is unusual.

• Hyperplasia of granulocyte and reticulocyte precursors is common.

• Bone marrow reticulin is usually increased, but collagen fibrosis is uncommon.

• Iron stores may be absent in the bone marrow. This may be due to gastrointestinal tract bleeding or menorrhagia. However, in ET, as in other myeloproliferative disorders, bone marrow iron stain results may be negative even when other studies do not support the presence of iron deficiency.

• Platelet aggregation studies

• The results of the prothrombin time and activated partial thromboplastin time studies are usually within reference ranges. The bleeding time may or may not be prolonged.

• Platelet aggregation study findings are abnormal and show impaired platelet aggregation to epinephrine, adenosine diphosphate, and collagen but not to ristocetin and arachidonic acid.

• Some patients may present with spontaneous platelet aggregation.

• Chemistries

• Chemistries reveal elevated uric acid levels in 25% of patients at diagnosis.

• Pseudohyperkalemia may occur, and falsely elevated phosphorous and acid phosphatase levels may be noted.

• Pseudohypoxemia may develop from extreme thrombocytosis.

• Vitamin B-12 levels are increased in 25% of patients.

• Cytogenetic study results are usually normal. Molecular studies (eg, polymerase chain reaction, Southern [genomic] blotting) may be used as sensitive means of excluding chronic myelogenous leukemia.

Imaging Studies:

• CT scans or ultrasonograms of the spleen may reveal splenomegaly in patients even when this condition is not physically detectable.

Other Tests:

• Elevation of C-reactive protein, fibrinogen, and interleukin-6 levels suggests the presence of secondary thrombocytosis, because these are acute-phase reactants.

• Conduct an RBC mass study to exclude polycythemia vera. In ET, the RBC mass is without abnormality.

• Conduct a sensitivity test to interleukin-3, which shows an increase in the formation of endogenous erythroid and/or megakaryocytic colonies and indicates the presence of abnormal hematopoietic progenitor cells (primarily a research tool).

Procedures:

• Bone marrow aspirate and biopsy

• A bone marrow aspirate and biopsy are useful. Use specialized needles to obtain the aspirate and biopsy material over the posterior iliac crest.

• Obtaining an aspirate over the sternum may also be helpful, although most physicians prefer the posterior iliac crest.

• Do not attempt to obtain a biopsy from the sternum.

In ET, as in other myeloproliferative disorders, bone marrow iron stain results may be negative when other studies do not support the presence of iron deficiency. For practical purposes, a ferritin level that is within the reference range or increased, along with an RBC mean corpuscular volume that is within the reference range, is sufficient to exclude reactive thrombocytosis secondary to iron deficiency and the possibility of polycythemia vera masked by iron deficiency.

	MEDICATION	Section 7 of 11
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ET treatment commonly includes the use of hydroxyurea, which is an antimetabolite similar in structure to naturally occurring compounds required for normal cell function. This structural similarity allows many of the antimetabolites to serve as substrates for important cellular enzymes. These substrates inhibit cell replication by direct inhibition of the enzymes needed for DNA replication or DNA repair or by incorporating directly into DNA. Tumors and healthy cells with high growth fractions (eg, bone marrow) are sensitive to inhibition by the antimetabolites. Anagrelide is an imidazoquinazoline drug that inhibits platelet aggregation. Anagrelide appears to decrease platelet counts by decreasing platelet production. Interferon alfa is a biologic response modifier, and phosphorous-32 is a radionuclide with direct myelosuppressive properties. Interferon alfa is not known to be teratogenic and does not cross the placenta, perhaps making it safe for use during pregnancy. Platelet counts rebound in most patientsafter stopping interferon. Platelet counts are reduced to less than 600,000/mL in 90% of cases after 3 months. Adjust drug dosing to achieve a platelet count within the reference range (target range, <450,000/mL).

Low-dose aspirin may be used to control microvascular symptoms.

Consider the patient's age, status, and adverse effect profile, in addition to the drug's cost, when choosing the treatment agent.

	MISCELLANEOUS	Section 9 of 11
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Medical/Legal Pitfalls:

• Failure to establish the diagnosis in patients with either hemorrhage or thrombosis

• Failure to administer cytoreductive therapy in patients older than 60 years or in those with a history of thrombosis: In high-risk patients, initiate platelet-reducing measures to prevent serious complications

Special Concerns:

• Pregnancy

• ET may increase the rate of pregnancy loss in women, primarily because of spontaneous abortions during the first trimester.

• Intrauterine death and intrauterine growth retardation may occur.

• Patients with a history of spontaneous abortion are clearly at increased risk of pregnancy loss.

• Spontaneous decreases in the platelet count may occur with a successful pregnancy, with the nadir in the second trimester. The cause of the decline is unclear and is only partially explained as owing to hemodilution.

• Treatment during pregnancy remains controversial; weigh potential teratogenic risks against risks to the mother.

• Consider treatment in patients at increased risk of fetal loss.

• Risk of teratogenicity may be lower with interferon than with other agents, and the drug appears to be well tolerated during pregnancy. Other therapies have included aspirin, hydroxyurea, and plateletpheresis.

• Women with histories of thrombosis and ET should receive cytoreductive therapy during pregnancy to minimize the risk of complications. Interferon is the preferred drug for this purpose. Therapy with interferon may be started before conception.

• Surgery

• Thrombohemorrhagic complications are possible in patients undergoing surgery.

• Before surgery, normalize platelet counts.

• Splenectomy has been associated with serious thrombohemorrhagic complications and should be avoided.