Preliminary Result of a Pilot Study of Apixaban in the Treatment of Splanchnic Vein Thrombosis

Introduction: Recently, direct oral anticoagulants (DOACs) are widely used in patients with venous thromboembolism. However, there is no sufficient data of DOACs in treatment of splanchnic vein thrombosis (SVT). In this study, we aimed to investigate the safety and efficacy of apixaban in treatment of SVT.

Methods: PAINT-SVT study was a prospective pilot study of the patients with newly diagnosed symptomatic acute SVT. Patients should not have contraindication to DOACs, and appropriate liver and renal function. Patients with chronic SVT, which includes evidence of cavernous formation, collateral circulation, or known SVT within 6 months were excluded.

Apixaban was administered at a dose of 10mg bid for 7 days, followed by 3 months of 5mg bid for initial treatment. With physicians’ decision, patients could be treated for 3 more months with apixaban at a dose of 2.5mg bid. Primary objective of this study was major bleeding (MB) according to International Society on Thrombosis and Haemostasis criteria. Key secondary objectives included clinically relevant non-major bleeding (CRNMB) and overall response rate (ORR).

Results: From Mar 2021 to Jun 2022, a total of 21 patients were enrolled in this study. Median age was 67 (range, 44 - 81) years and 12 patients (57.1%) were males. This study included 17 patients (81.0%) with liver cirrhosis (LC), and all but one patient had child-push score of A. Four patients (19.0%) had underlying malignancies (1 lymphoproliferative disease, 1 gastrointestinal stromal tumor, 1 hepatocellular carcinoma, and 1 follicular lymphoma). With median time on anticoagulation of 92 (range, 3.0 - 184.0) days, 3 patients experienced MB and 6 patients experienced CRNMB. CRNMB occurred mostly within 1 month of anticoagulation, while MB occurred more wide range of time point during anticoagulation. Although the interpretation is limited due to the small number of samples, bleeding event occurred exclusively in LC patients.

Of 21 patients, 18 patients were evaluable except for 2 patients who discontinued before the completion of initial treatment due to bleeding and 1 patient who did not completed 3 months of anticoagulation at the time of analysis. Radiologically, ORR was 61.1% including 5 patients (27.8%) with complete remission (CR) and 6 patients (33.3%) with partial remission (PR). Among 17 patients with LC, 15 patients were evaluable and ORR was 66.7% (CR, 26.7% and PR, 40.0%). Among patients who completed 3 months of initial treatment, 14 patients received additional 3 months of extended treatment and 11 patients completed extended treatment. So far, 2 patients showed improvement of response (PR to CR) and 1 patient showed thrombus progression during the treatment.

Conclusions: In patients with SVT, apixaban can be used effectively and safely. However, caution is warranted for bleeding complications especially in patients with underlying LC, even in the early stage.

No relevant conflicts of interest to declare.