In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology
In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiologyControlled studies in polycythemia vera (PV) have demonstrated the value of aggressive phlebotomy, aspirin, and cytoreductive therapy in preventing thrombotic complications. [1][2]2][3] In the European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) prospective study of 1638 patients diagnosed by using criteria from the Polycythemia Vera Study Group, risk factors for all thromboses were age older than 65 years and prior thrombotic events. 4However, diagnosis criteria for PV have since undergone substantial revision in the World Health Organization system for disease classification, with special emphasis on bone marrow morphology and JAK2 mutational status. 5 Accordingly, this study includes 1545 patients with strictly World Health Organization-defined PV who were diagnosed and followed up in 7 centers in Italy, Austria, and the United States that belong to the International Working Group for Myeloproliferative Neoplasms.The study was approved by the institutional review board at each institution.Objectives were to (1) describe the rate of thrombosis, (2) report the sites and frequency of recurrences after a first arterial or venous event, and (3) identify risk factors for arterial vs venous thrombosis.The characteristics of the cohort recruited at diagnosis (Table 1) reflect the heterogeneity of epidemiologic and clinical features that are found in the routine clinical practice of diagnosing PV.Arterial and venous thrombosis history before or at diagnosis was documented in 246 (16%) and 114 (7.4%) patients, respectively.The frequencies of arterial and venous thrombosis were lower than those recorded in the ECLAP study 4 (27% and 11%, respectively) but comparable to those reported in the recent Cyto-PV study 2 (arterial 17%, venous 12%).Major hemorrhage before or at diagnosis was reported in 4.5% of patients in this study vs 8% in ECLAP and 1.7% in Cyto-PV cohorts.The prevalence of hypertension, hyperlipidemia, diabetes, and tobacco use was similar to that reported in the ECLAP and Cyto-PV studies.Median follow-up was 6.9 years, and treatment included aspirin (84%) and cytoreductive agents (73%), in addition to phlebotomy (Table 1).Postdiagnosis total major thrombosis rate was 2.62% patients per year, lower than that reported in the ECLAP trial (4.4% patients per year) but comparable to the rate in the Cyto-PV study (2.7% patients per year) in which management of cardiovascular risk factors was more intensive than in the ECLAP study.Arterial or venous thrombosis occurred in 184 (12%; rate: 1.59% patients per year) and 137 (9%; rate: 1.05% patients per year) patients, respectively.In addition, in 75% of the patients, arterial events were associated with subsequent arterial events, and in the remaining 25%, they were associated with venous thrombosis including splanchnic vein events.Conversely, in patients with prior venous events, 61% had venous recurrences and 39% had arterial recurrences.In multivariable analysis, previous arterial event (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.2 to 2.4) and hypertension (HR, 1.6; 95% CI, 1.2 to 2.2) were significantly associated with subsequent arterial events whereas previous venous event (HR, 2.6; 95% CI, 1.5 to 4.4) and age $65 years (HR, 1.7; 95% CI, 1.2 to 2.5) were significant predictors of future venous thrombosis.