Abstract
Background: Treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients.
Methods: We retrospectively included SVT patients treated with VKAs and followed by 37 Italian Anticoagulation Clinics until June 2013. All documented bleeding and thrombotic events were reviewed by a Central Independent Adjudication Committee. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented.
Results: 375 patients with SVT on VKA treatment were included (median age 53 years; 54.7% males). The most common risk factors were: hematological diseases (21.6%), hepatic cirrhosis (15.2%), solid cancer (10.7%), recent abdominal surgery (8.0%) and intra-abdominal inflammation or infection (6.7%); in 37.1% SVT was unprovoked. The therapeutic INR target range was 2.0-3.0 in 353 patients (94.1%).
During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% CI, 0.75-2.06) per 100 patient-years. All bleeding patients were receiving warfarin with INR target range 2.0-3.0 and almost two thirds of bleeding complications occurred with therapeutic INR. One MB was fatal, corresponding to a case-fatality rate of 6.7%. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, adjusted for age and sex and stratified by Center, the presence of esophageal varices emerged as independent predictor of MB (HR 4.9; 95% CI, 1.4-17.1), while inflammatory bowel diseases were borderline statistically significant (HR 15.2; 95% CI, 0.99-233.1).
The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years, including 9 venous thrombosis and 7 arterial thrombosis. The mortality rate was 0.83 (95% CI, 0.45-1.54) per 100 patient-years.
Conclusions: In designated SVT patients, oral anticoagulant treatment was safe, with a reported incidence of major bleeding less than 2% per year and a reasonable case-fatality rate. It is therefore of utmost importance to accurately select which SVT patients are suitable to be prescribed with VKAs.
Ageno:Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; STAGO: Honoraria. Rodeghiero:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Suppremol: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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