Advances and challenges in the management of essential thrombocythemia

Abstract

The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early myelofibrosis (MF), which has helped to identify a more homogenous population for the diagnosis with longer survival and much less transformation to overt MF. The recent finding of a new mutation (CALR), which is mutually exclusive with JAK2 and MPL mutations, adds to the characterization of ET patients, since there are important phenotypic differences between the mutation types. CALR patients are younger, have lower white blood cell counts (WBC) and a lower thrombosis incidence. A growing field of interest is the state of hypercoagulation due to dysfunction of hemostatic systems, cell-cell interaction and hereditary prothrombotic traits. Activation of platelets, WBC and endothelial cells has been found, making the whole intravascular milieu prothrombotic. Several risk score models, based on retrospective studies, have been developed lately, distinguishing patient groups with graded risk for complications and death. Even if these may be helpful in evaluating patients, they have not been validated in prospective studies and there are not enough data to support their use as a basis for treatment algorithms. The traditional risk factors age, previous thrombosis and platelets >1500 × 10(9)/l are still recommended for the distinction between high risk and low risk ET and the decision to give cytoreductive therapy. However, cardiovascular (CV) risk factors add to thrombosis risk and should be considered both for specific treatment in any risk group and for upgrading low risk patients with high CV risk to an intermediary group where active therapy with aspirin and cytoreduction may be considered. First-line cytoreductive therapy differs with age; in younger patients interferon (IFN) or anagrelide are preferable, in older patients hydroxycarbamide (HC). Second-line therapy for younger patients is HC, for older patients IFN or anagrelide (ANA). JAK2 inhibitors may be suitable in rare cases with symptoms not responding to other therapy.

Keywords: essential thrombocythemia; myeloproliferative disorders.

Figure 1.

WHO 2008 criteria for the diagnosis of ET. CML, chronic myelogenous leukemia; ET, essential thrombocythemia; MDS, myelodysplastic syndromes; PMF, primary myelofibrosis; PV, polycythemia vera; WHO, World Health Organization.

Figure 2.

Suggested algorithm for diagnostic work-up of sustained thrombocytosis. Some labs perform all three mutation analyses upfront. BMB, bone marrow biopsy; ET, essential thrombocythemia; MPN, myeloproliferative neoplasm; PMF, primary myelofibrosis; WHO, World Health Organization.

Figure 3.

Suggested management of true ET. In patients with previous hemorrhage: avoid combination of aspirin and anagrelide. *Caution with aspirin if platelets are>1000 × 10⁹/l. CV, cardiovascular; ET, essential thrombocythemia; HC, hydroxycarbamide; HU, hydroxyurea; IFN, interferon; WHO, World Health Organization.