How I treat patients with polycythemia vera

Abstract

The clinical course of polycythemia vera (PV) is marked by a high incidence of thrombotic complications; fibrotic and leukemic disease transformations are additional causes of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis; leukocytosis and high JAK2 V617F allele burden are currently being investigated for additional prognostic value in this regard. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Lowrisk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, and the drug of choice is hydroxyurea because of its efficacy in preventing thrombosis and low leukemogenicity. Interferon-alpha should be reserved for selected categories of patients due to high cost and toxicity. The demonstration of JAK2 V617F mutation in the vast majority of PV patients opens the avenue for the development of promising new molecularly targeted drugs. (Blood. 2007;109: 5104-5111)

Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders

“…50,55,70,72,[82][83][84] Taking into account that these cardiovascular risk factors may have additional influence on the expected risk of thrombosis in PV and ET, patients with such risk factors are usually considered to belong to an intermediate-risk category. 85,86 Nevertheless, the use of cytoreductive treatment is not recommended in these patients, but an appropriate management of the reversible risk factors is mandatory.…”

A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications

“…2 Among these, age, cardiovascular risk factors and genetic thrombophilia are independent from the JAK2 mutational status. Cytoreductive therapy as well as aspirin are effective treatments for thrombosis prevention, 14,31 therefore masking the potential thrombophilic role of the mutation. Two large studies on PV did not reveal a relationship between JAK2 mutant allele burden and thrombosis, 10,25 while one found a correlation.…”

Thrombocytosis and Thrombosis

“…4,5,31,[49][50][51][52][53][54] Improvement or resolution of underlying disease results in normalization of platelet count in reactive thrombocytosis; sometimes, particularly if generic cardiovascular risk factors are present, prolonged increase of platelet count after splenectomy for any cause is managed with aspirin for thrombosis prophylaxis, but no prospective trial supporting this practice exists. As concerns primary thrombocytosis, the lack of evidence-based correlation with occurrence of thrombotic events translates into the lack of a clear rationale for correcting platelet count to normal levels as an effective measure to prevent thrombosis.…”