Platelet activation and inhibition in polycythemia vera and essential thrombocythemia.
ABSTRACT Persistently enhanced platelet activation has been characterized in Polycythemia Vera (PV) and Essential Thrombocythemia (ET) and shown to contribute to a higher risk of both arterial and venous thrombotic complications. The incidence of major bleeding complications is also somewhat higher in PV and ET than in the general population. Although its efficacy and safety was assessed in just one relatively small trial in PV, low-dose aspirin is currently recommended in practically all PV and ET patients. While for most patients with a thrombosis history the benefit/risk profile of antiplatelet therapy is likely to be favorable, in those with no such history this balance will depend critically on the level of thrombotic and hemorrhagic risks of the individual patient. Recent evidence for a chemopreventive effect of low-dose aspirin may tilt the balance of benefits and harm in favor of using aspirin more broadly, but the potential for additional benefits needs regulatory scrutiny and novel treatment guidelines. A clear pharmacodynamic rationale and analytical tools are available for a personalized approach to antiplatelet therapy in ET, and an improved regimen of low-dose aspirin therapy should be tested in a properly sized randomized trial.
SourceAvailable from: Atul C Mehta
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ABSTRACT: The BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are associated with an increased risk of both venous and arterial thromboembolic events. Thromboses may be the presenting clinical feature of an MPN or may occur during the course of the disease. Treatment comprises anticoagulant and antiaggregant agents as in non- MPN thromboses, and treatment of the particular MPN. The duration of anticoagulant treatment that is required for MPN thrombosis is unknown. This study was performed to survey the opinion of hematologists who treat patients with MPN regarding the duration of anticoagulation or antiaggregant therapy in patients in whom thrombosis is the presenting feature of MPN. Five clinical scenarios in which thromboembolism (cerebral vein thrombosis, pulmonary embolism, cerebrovascular accident, splanchnic vein thrombosis, portal vein thrombosis) was a presenting feature of MPN were created using a web-based tool and were sent by email to hematologists in Israel, Italy and England and to hematologists identified as key opinion leaders in the field of MPN. Physicians were asked to recommend duration of anticoagulation and/or aspirin use choosing from 4 alternatives provided. Seventy-three physicians responded to the survey. 42 physicians considered MPNs to be their main area of clinical interest, and 31 did not. 21 physicians saw more than 20 MPN patients per week, and 50 physicians had been in hematology practice for more than 10years. Responses regarding the duration of anticoagulation and/or the use of aspirin varied for all of the clinical vignettes. Neither physician area-of-interest, volume of MPN patients treated nor years in practice were related to the responses obtained. This study demonstrates that hematologists, including those specializing in MPNs, lack consensus in their approach to the long-term treatment of thromboses as the presenting feature of an MPN. Controlled clinical studies are needed to inform appropriate decision making in this area.Thrombosis Research 05/2014; 134(2). DOI:10.1016/j.thromres.2014.04.032 · 2.43 Impact Factor
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ABSTRACT: To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN-CVT) to 87 with MPN and other venous thrombosis (group MPN-VT) and 178 with MPN and no thrombosis (group MPN-NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN-CVT and MPN-VT than in MPN-NoT group (p=0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (p=0.059). Compared to MPN-VT, MPN-CVT patients had a higher rate of recurrent thrombosis (42% vs 25%, p=0.049) despite a shorter median follow-up period (6.1 vs 10.3 years, p=0.019), a higher long-term antithrombotic (94% vs 84%, p=0.099) and a similar cytoreductive treatment (75% vs 72%, p=0.745). The incidence of recurrent thrombosis was double in MPN-CVT than in MPN-VT group (8.8% and 4.2% patient-years, p=0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive and antithrombotic treatment (HR 1.97, 95%CI 1.05-3.72 and 2.09, 1.09-4.00, respectively).American Journal of Hematology 07/2014; 89(11). DOI:10.1002/ajh.23809 · 3.48 Impact Factor