title: Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria.
abstract: 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.
authors.affiliation: Division of Hematology, Research Foundation, Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Finazzi
authors.forename: A
authors.initials: A
authors.lastname: Carobbio
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: F
authors.initials: F
authors.lastname: Passamonti
authors.forename: E
authors.initials: E
authors.lastname: Rumi
authors.forename: M
authors.initials: M
authors.lastname: Ruggeri
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: M L
authors.initials: ML
authors.lastname: Randi
authors.forename: I
authors.initials: I
authors.lastname: Bertozzi
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: E
authors.initials: E
authors.lastname: Antonioli
authors.forename: H
authors.initials: H
authors.lastname: Gisslinger
authors.forename: V
authors.initials: V
authors.lastname: Buxhofer-Ausch
authors.forename: N
authors.initials: N
authors.lastname: Gangat
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: T
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000150:complications* / Q000175:diagnosis; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000175:diagnosis; D014944:World Health Organization