In an international study of 1104 patients with
essential thrombocythemia (ET), a histological review according to the 2008 World Health Organization (WHO) criteria confirmed ET in 891 patients (WHO-ET, 81%), and revised the diagnosis to prefibrotic
primary myelofibrosis (PMF) in 180 patients (PMF, 16%). Major
bleeding during follow-up occurred in 55 (6%) WHO-ET and 21 (12%) PMF patients (P = 0.009), at a rate of 0.79 and 1.39% patients per year, respectively, (P = 0.039). In a multivariable analysis, predictors of
bleeding included diagnosis of PMF (P = 0.05; hazard ratio (HR) 1.74),
leukocytosis (P = 0.04; HR 1.74), previous
hemorrhage (P = 0.025; HR 2.35) and
aspirin therapy (P=0.001; HR 3.16). The analysis restricted to patients with WHO-ET confirmed previous
hemorrhage (P = 0.043; HR 1.92) and
aspirin (P=0.027; HR 2.24) as independent risk factors. The current study reveals that major
bleeding associated with
thrombocytosis might be relatively specific to PMF, as opposed to WHO-defined ET. Furthermore, it shows that low-dose
aspirin exacerbates these hemorrhagic events of PMF. In contrast,
thrombocytosis per se was not a risk factor for
bleeding; however, low-dose
aspirin had a synergistic hemorrhagic effect unmasking the
bleeding tendency of patients with extreme
thrombocytosis. These observations carry significant therapeutic implications in these two WHO entities.