Page 98 - Haematologica May 2022

Ferrata Storti Foundation
Haematologica 2022 Volume 107(5):1106-1110
Hemorrhage in patients with polycythemia vera receiving aspirin with an anticoagulant: a prospective, observational study
Jeffrey I. Zwicker,1 Dilan Paranagama,2 David S. Lessen,3 Philomena M. Colucci,2 and Michael R. Grunwald4
1Beth Israel Deaconess Medical Center, Division of Hematology, Harvard Medical School, Boston, MA; 2Incyte Corporation, Wilmington, DE; 3Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL and 4Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
ABSTRACT
Polycythemia vera (PV) is associated with increased risk of thrombo- sis and hemorrhage. Aspirin, recommended for primary thrombo- prophylaxis, is often combined with anticoagulants during manage- ment of acute thrombotic events. The safety of dual antiplatelet and anticoagulant therapy is not established in PV. In a prospective, observa- tional study, 2,510 patients with PV were enrolled at 227 sites in the United States. Patients were monitored for the development of hemor- rhage and thrombosis after enrollment. A total of 1,602 patients with PV received aspirin with median follow-up of 2.4 years (range, 0-3.6 years). The exposure-adjusted rate of all hemorrhages in patients receiving aspirin alone was 1.40 per 100 patient-years (95% confidence interval [CI]: 0.99-1.82). The combination of aspirin plus anticoagulant was asso- ciated with an incidence of hemorrhage of 6.75 per 100 patient-years (95% CI: 3.04-10.46). The risk of hemorrhage was significantly greater in patients receiving the combination of aspirin and anticoagulant com- pared with aspirin alone (total hemorrhages, hazard ratio [HR]: 5.83; 95% CI: 3.36-10.11; P<0.001; severe hemorrhage, HR: 7.49; 95% CI: 3.02-18.62; P<0.001). Periods of thrombocytosis (>600×109/L) were asso- ciated with an increased risk of hemorrhage (HR: 2.25; 95% CI: 1.16- 4.38; P=0.02). Rates of hemorrhage were similar for aspirin in combina- tion with warfarin or direct-acting oral anticoagulants. We conclude that the combination of aspirin and anticoagulants is associated with signifi- cantly increased risk of hemorrhage in patients with PV (clinicaltrials gov. Identifier: NCT02252159).
Introduction
Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) usually involving a mutation of the Janus kinase 2 gene and characterized phenotypically by an increased risk of thrombosis and hemorrhage.1 Low-dose aspirin effectively reduces the rate of arterial and venous thrombosis and is recommended for primary throm- boprophylaxis in patients diagnosed with PV.2,3 Despite the administration of antiplatelet and cytoreductive therapy, approximately 25% of patients with PV ulti- mately develop thrombotic complications.4 The optimal approach to the manage- ment of thrombosis in patients with MPN is undefined. Anticoagulation is recom- mended for the acute treatment of thrombosis3 but is associated with a recurrent thrombosis incidence of 5-6 events per 100 patient-years5,6 and major hemorrhage incidence of 1-3 events per 100 patient-years.5-7 Due to the high rates of recurrent thrombotic events, aspirin is often continued along with therapeutic anticoagulation, but the relative safety of combined anticoagulant-antiplatelet therapy is not estab- lished. We evaluated the rates of hemorrhage among patients with PV receiving anti- coagulation with or without aspirin who were enrolled in a multicenter, prospective, observational study.
Myeloproliferative Disorders
Correspondence:
JEFFREY ZWICKER
jzwicker@bidmc.harvard.edu
Received: April 21, 2021. Accepted: June 16, 2021. Pre-published: June 24, 2021.
https://doi.org/10.3324/haematol.2021.279032 ©2022 Ferrata Storti Foundation
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