Development and validation of an International Prognostic Score of thrombosis in WHO-Essential Thrombocythemia (IPSET-thrombosis).

Accurate prediction of thrombosis in essential thrombocythemia (ET) provides the platform for prospective studies exploring preventive measures. Current risk stratification for thrombosis in ET is two-tiered and considers low- and high-risk categories, based on the respective absence or presence of either age >60 years or history of thrombosis. In an international study of 891 patients with WHO-defined ET, we identified additional independent risk factors including cardiovascular risk factors and JAK2V617F. Accordingly, we assigned risk scores based on multivariable analysis-derived hazard ratios (HR) to age >60 years (HR 1.5; one point), thrombosis history (HR 1.9; two points), cardiovascular risk factors (HR 1.6; one point) and JAK2V617F (HR 2.0; two points) and subsequently devised a three-tiered prognostic model (low-risk, <2 points; intermediate-risk, 2 points; and high-risk, >2 points) using a training set of 535 patients and validated the results in the remaining cohort (n=356; internal validation set) as well as in an external validation set (n=329). Considering all three cohorts (n=1,220), the three-tiered new prognostic model (low-risk n=474 vs. intermediate-risk n=471 vs. high-risk n=275), with a respective thrombosis risk of 1.03%pts/yr vs. 2.35%pts/yr vs. 3.56%pts/yr, outperformed the two-tiered (low-risk 0.95%pts/yr vs. high-risk 2.86%pts/yr) conventional risk stratification in predicting future vascular events.