Anticoagulation Therapy for Venous Thrombotic Events in Patients with Myeloproliferative Neoplasms
Authors: Lavi Noa , Koren-Michowitz Maya , Leader Avi , Shacham-Abulafia Adi , Shapira Shirley , Dally Najib , Chubar Evgeni , Mishchenko Elena , Ellis Martin H. 
Published: October 2019

Introduction: Philadeliphia chromosome negative myeloproliferative neoplasms (MPNs) [polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis (MF)] are characterized by an increased risk of venous thromboembolism (VTE). In PV the VTE incidence has been reported to be 7.4% before or at diagnosis and 9% after diagnosis (Tefferi A et al, 2013). In general, the first VTE event provoked by a reversible risk factor warrants 3-6 months of anticoagulation, while VTE associated with active cancer is usually treated until remission. There are no controlled studies evaluating the optimal duration of anticoagulant therapy in MPN patients (pts). A consensus statement regarding prophylaxis and management of VTE in MPN patients (Hernández-Boluda et al, 2015) has recommended permanent anticoagulation only in pts with very high thrombotic risk [recurrent VTE, Budd Chiari Syndrome (BCS), major thrombophilia].

This retrospective study aims to identify characteristics of MPN pts receiving long-term anticoagulant therapy after VTE and to determine the VTE recurrence rate in pts on long-term versus short-term anticoagulation after an initial VTE.

Methods: Pts with MPN diagnosed according to World Health Organization criteria, with a history of VTE [cerebral sinus, deep vein thrombosis (DVT), pulmonary embolism (PE), BCS, spleno-portal or mesenteric vein thrombosis] within 2 years prior to MPN diagnosis or at any time thereafter were identified in 8 centers that are members of the Israel MPN Working Group. VTE was diagnosed at least 1 year before data collection. Clinical characteristics and treatment data were recorded. Long-term anticoagulation was defined as therapy for >1 year with any anticoagulant.

Results: Ninety one MPN pts [31 (34%) - PV, 35 (38%) - ET, 18 (20%) - MF, 7 (8%) - MPN unclassified] with VTE fulfilling study criteria, were included in the analysis. Eighty two percent were JAK2V617F positive (PV-97%, ET-81%, MF-71%, MPN-unclassified-57%). Forty nine pts underwent thrombophilia testing, of whom 21 (43%) had coexistent thrombophilia.

Twenty six pts (28.6%) were treated with anticoagulants for less than a year (Group 1), while 65 (71.4%) pts received long-term anticoagulation (Group 2). At time of VTE diagnosis, there were no differences between the groups regarding age, gender, type of MPN, JAK2 V617F mutational status or blood counts.VTE types were the same in both groups, apart from BCS, which was found in Group 2 only (0 vs 16.9%, p=0.029). Thrombophilia testing was done in 66% of pts from Group2 and in 32% of pts from Group 1. Long-term anticoagulation was used in 86% of pts with coexisting thrombophilia and in83% of pts without thrombophilia. Reasons for anticoagulation cessation were: bleeding (n=1), hematologic control (n=8), a transient additional risk for thrombosis at time of VTE (n=3), other reasons such as poor compliance (n=9) and unknown (n=5).

At a median follow-up of 6.7 years, there were no differences in recurrent VTE rates and mortality rates between Group 1 and Group 2 (12.5% vs 14.5%, respectively, p=1 and 11.5% vs 13.8%, respectively, p=1).

When comparing pts with recurrent VTE vs those without recurrent VTE, there were no differences regarding MPN type, JAK2 V617F mutational status, type of VTE or coexisting thrombophilia. None of the pts who stopped anticoagulation after achieving disease control had VTE recurrence.

Conclusions: Most MPN pts with VTE received long-term anticoagulant therapy (71.4%). There were no differences in clinical characteristics between those who were treated with long-term anticoagulation versus those who were not apart from BCS patients who were treated indefinitely. We found no difference in the rates of VTE recurrence between patients receiving short- vs long-term anticoagulation however confounding variables such as hematologic control of the MPN may account for this finding, therefore, anticoagulation therapy until attainment of hematologic control may be considered. Prospective clinical trials are needed to evaluate the optimal duration of anticoagulation for prevention of recurrent VTE in MPN pts.

Disclosures

Leader: Novartis: Research Funding.