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1314 Part X: Malignant Myeloid Diseases Chapter 85: Essential Thrombocythemia 1315

TABLE 85–6. Risk Factors for Complications in Essential Thrombocythemia
Thrombosis Hemorrhage Myelofibrotic Transformation Acute Myeloid Leukemia
Age >60 years Marrow fibrosis ‡ Disease duration Disease duration
Prior thrombosis Thrombocytosis † Anagrelide therapy ¶ Genotoxic therapy
Cardiovascular risk* Leucocytosis † Marrow fibrosis ‡ Use of >1 cytoreductive agent
Leukocytosis †
Marrow fibrosis ‡
JAK2 V617F mutation §
*Diabetes, hypertension, hypercholesterolemia or tobacco use.
† During followup.
‡ At diagnosis.
§ Venous and arterial thrombosis.
¶ Compared with hydroxyurea.

should cytoreductive therapy be required during pregnancy. Although management paradigms have changed significantly over the last 10 to
studies in ET patients are lacking, thromboprophylaxis appears safe in 20 years, including more aggressive intervention to prevent thrombo-
pregnancy (e.g., with low doses of low-molecular-weight heparin), and sis and decreasing use of leukemogenic agents. These changes, which
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may be considered for patients with a history of thrombosis or preg- may be related to observed improvements in patient outcomes in recent
nancy loss; in those with prior thrombosis, treatment should be con- years, render some long-term followup studies difficult to interpret.
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tinued for 6 weeks postpartum. Pregnant ET patients should ideally be A number of predictive factors for thrombotic complications have
managed in a center where regular fetal monitoring can be performed, been identified (Table 85–6), the best established of which are age older
with good communication between the obstetric, hematology, and than 60 years or a history of previous thrombosis. Factors independently
anesthetic departments. Pregnancy does not appear to affect the natu- associated with decreased overall survival in ET include history of prior
ral history of the disease, although the platelet count often falls during thrombosis, anemia and leukocytosis, the latter two factors likely rep-
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gestation. In animal studies, hydroxyurea is associated with reduced resenting markers of more advanced disease. Additional factors asso-
spermatogenesis and genetic damage to spermatogonia. Male patients ciated with an increased risk of thrombosis include predisposition to
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requiring cytoreductive treatment should therefore consider interfer- atherosclerotic disease (diabetes, hypertension, hypercholesterolemia,
on-α therapy prior to attempted conception. or tobacco use), presence of a JAK2 V617F mutation or increased marrow
fibrosis at diagnosis (see section “Thrombosis”). At the present time,
age older than 60 years or history of previous thrombosis are generally
Surgery considered to mandate cytoreductive therapy in ET patients. Whether
Although thrombotic and bleeding complications appear increased additional factors, such as presence of a JAK2 mutation, can be used to
in ET patients undergoing surgical procedures, it is not clear whether improve patient stratification is yet to be tested formally in a clinical trial.
these risks can be ameliorated by specific therapeutic interventions. In contrast to thrombotic complications, there are few identifi-
In general, antiplatelet agents should be stopped 7 to 10 days prior to able factors that predict for progression to PMF or acute leukemia. The
major surgery or surgery to critical sites, and recommenced as soon as incidence of both complications increases progressively with disease
the surgeon is confident of secure hemostasis. Postoperative thrombo- duration. Choice of therapy also plays a role, with anagrelide increas-
prophylaxis should be administered according to local protocols. For ing the risk of myelofibrotic transformation compared to hydroxyurea
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patients receiving cytoreductive therapy, control of blood counts should and genotoxic agents increasing the risk of leukemia, especially when
be optimized preoperatively and interruptions in therapy kept to a min- used sequentially with hydroxyurea. Marrow fibrosis at diagnosis was
imum. For patients not receiving treatment, temporary cytoreductive associated with an increased risk of subsequent PMF in a prospective
therapy may be considered on a case-by-case basis, taking into account study, but other markers, including the presence of different somatic
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the individual’s thrombotic risk profile, the degree of thrombocytosis, mutations, have failed to show a consistent association with either mye-
and the nature of the surgery. lofibrotic or leukemic transformation.
Splenectomy in ET patients generally results in an increase in the
platelet count and also in increased thrombotic and hemorrhagic com-
plications. Normalization of the platelet count is therefore advisable for REFERENCES
all ET patients prior to elective splenectomy. Thromboprophylaxis and 1. Epstein E, Geoedel A: Hemorrhagic thrombocythemia with cascular, sclerotic spleen.
daily monitoring of bloods counts is recommended during the postop- Virchows Archiv A Pathol Anat Histopathol 293:233, 1934.
erative period. 2. Fialkow PJ, Faguet GB, Jacobson RJ, et al: Evidence that essential thrombocythemia is a
clonal disorder with origin in a multipotent stem cell. Blood 58:916, 1981.
3. McNally RJ, Rowland D, Roman E, Cartwright RA: Age and sex distributions of hema-
COURSE AND PROGNOSIS 4. Mesa RA, Silverstein MN, Jacobsen SJ, et al: Population-based incidence and survival
tological malignancies in the U.K. Hematol Oncol 15:173, 1997.
figures in essential thrombocythemia and agnogenic myeloid metaplasia: An Olmsted
There is a lack of good quality prospective data concerning long-term County Study, 1976-1995. Am J Hematol 61:10, 1999.
survival in ET. Data from cancer registries and retrospective studies 5. Anderson RE, Hoshino T, Yamamoto T: Myelofibrosis with myeloid metaplasia in sur-
indicate that overall survival is reduced compared with population vivors of the atomic bomb in Hiroshima. Ann Intern Med 60:1, 1964.
controls. 93–95 This excess mortality results from disease complications 6. Kralovics R, Stockton DW, Prchal JT: Clonal hematopoiesis in familial polycythemia
vera suggests the involvement of multiple mutational events in the early pathogenesis
such as thrombosis and transformation to PMF or AML. However, of the disease. Blood 102:3793, 2003.

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