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: Alberto Alvarez-Larrán, Arturo Pereira, Paola Guglielmelli, Juan Carlos Hernández-Boluda, Eduardo Arellano-Rodrigo, Francisca Ferrer-Marín, Alimam Samah, Martin Griesshammer, Ana Kerguelen, Bjorn Andreasson, Carmen Burgaleta, Jiri Schwarz, Valentín García-Gutiérrez, Rosa Ayala, Pere Barba, María Teresa Gómez-Casares, Chiara Paoli, Beatrice Drexler, Sonja Zweegman, Mary F McMullin, Jan Samuelsson, Claire Harrison, Francisco Cervantes, Alessandro M Vannucchi, Carlos Besses
• Journal: Haematologica (Haematologica) Vol. 101 Issue 8 Pg. 926-31 (08 2016) ISSN: 1592-8721 [Electronic] Italy
• PMID: 27175028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Calreticulin
• Platelet Aggregation Inhibitors
• Janus Kinase 2

Topics

• Adolescent
• Adult
• Calreticulin (genetics)
• Child
• Female
• Hemorrhage (epidemiology, etiology)
• Humans
• Incidence
• Janus Kinase 2 (genetics)
• Leukocyte Count
• Male
• Middle Aged
• Mutation
• Phenotype
• Platelet Aggregation Inhibitors (therapeutic use)
• Thrombocythemia, Essential (complications, diagnosis, genetics)
• Thrombosis (epidemiology, etiology, prevention & control)
• Time-to-Treatment
• Treatment Outcome
• Watchful Waiting
• Young Adult