title: Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation.
abstract: The role of antiplatelet therapy as primary prophylaxis of thrombosis in low-risk essential thrombocythemia has not been studied in randomized clinical trials. We assessed the benefit/risk of low-dose aspirin in 433 patients with low-risk essential thrombocythemia (271 with a CALR mutation, 162 with a JAK2(V617F) mutation) who were on antiplatelet therapy or observation only. After a follow up of 2215 person-years free from cytoreduction, 25 thrombotic and 17 bleeding episodes were recorded. In CALR-mutated patients, antiplatelet therapy did not affect the risk of thrombosis but was associated with a higher incidence of bleeding (12.9 versus 1.8 episodes per 1000 patient-years, P=0.03). In JAK2(V617F)-mutated patients, low-dose aspirin was associated with a reduced incidence of venous thrombosis with no effect on the risk of bleeding. Coexistence of JAK2(V617F)-mutation and cardiovascular risk factors increased the risk of thrombosis, even after adjusting for treatment with low-dose aspirin (incidence rate ratio: 9.8; 95% confidence interval: 2.3-42.3; P=0.02). Time free from cytoreduction was significantly shorter in CALR-mutated patients with essential thrombocythemia than in JAK2(V617F)-mutated ones (median time 5 years and 9.8 years, respectively; P=0.0002) and cytoreduction was usually necessary to control extreme thrombocytosis. In conclusion, in patients with low-risk, CALR-mutated essential thrombocythemia, low-dose aspirin does not reduce the risk of thrombosis and may increase the risk of bleeding.
authors.affiliation: Hematology Department, Hospital del Mar, IMIM, UAB, Barcelona, Spain 95967@parcdesalutmar.cat.
authors.forename: Alberto
authors.initials: A
authors.lastname: Alvarez-Larrán
authors.affiliation: Hematotherapy and Hemostasis Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Center for Research and Innovation of MPN (CRIMM); AOU Careggi, and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.affiliation: Hematology Department, Hospital Clínico, Valencia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Hernández-Boluda
authors.affiliation: Hematotherapy and Hemostasis Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arellano-Rodrigo
authors.affiliation: Hematology and Medical Oncology Department, Hospital Morales Messeguer, IMIB-Arrixaca, UCAM, Murcia, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Ferrer-Marín
authors.affiliation: Haematology Department, Guys' and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Alimam
authors.initials: A
authors.lastname: Samah
authors.affiliation: Hematology, Oncology & Palliative Care, Johannes Wesling Academic Medical Center, University of Hannover Teaching Hospital, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Griesshammer
authors.affiliation: Hematology Department, Hospital La Paz, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Kerguelen
authors.affiliation: Hematology Section, Uddevalla Hospital, NU Hospital Group, Sweden.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Andreasson
authors.affiliation: Hematology Department, Hospital Príncipe de Asturias, Alcalá de Henares, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Burgaleta
authors.affiliation: Institute of Hematology & Blood Transfusion, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Schwarz
authors.affiliation: Hematology Department, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: García-Gutiérrez
authors.affiliation: Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Ayala
authors.affiliation: Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.affiliation: Hematology Department, Hospital Dr. Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Gómez-Casares
authors.affiliation: Center for Research and Innovation of MPN (CRIMM); AOU Careggi, and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Paoli
authors.affiliation: Division of Hematology, University Hospital Basel, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Drexler
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Mary F
authors.initials: MF
authors.lastname: McMullin
authors.affiliation: Department of Clinical Science and Education, Karolinska Institute, South Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Samuelsson
authors.affiliation: Haematology Department, Guys' and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: Center for Research and Innovation of MPN (CRIMM); AOU Careggi, and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: Hematology Department, Hospital del Mar, IMIM, UAB, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Besses
mesh_terms: D000293:Adolescent; D000328:Adult; D037282:Calreticulin / Q000235:genetics*; D002648:Child; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D053614:Janus Kinase 2 / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D061665:Time-to-Treatment; D016896:Treatment Outcome; D057832:Watchful Waiting; D055815:Young Adult
chemical_list: D037282:Calreticulin; D010975:Platelet Aggregation Inhibitors; D053614:Janus Kinase 2