Risk of bleeding and arterial cardiovascular events in patients with splanchnic vein thrombosis in Denmark: a population-based cohort study

Abstract

Background: Little is known about adverse events following splanchnic vein thrombosis. Venous thromboembolism has been associated with increased risks of bleeding and arterial cardiovascular events. To learn more about the clinical course of splanchnic vein thrombosis, we examined the risks of bleeding and arterial cardiovascular events in patients with the disease, and compared them with the risks in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) and individuals from the general population.

Methods: In this population-based cohort study, we used data for all patients with a diagnosis of splanchnic vein thrombosis recorded in the Danish National Patient Registry (DNPR) between Jan 1, 1994, and Nov 30, 2013 (cumulative source population 7 310 450 individuals). We created two comparison cohorts using data from the DNPR and the Civil Registration System for the same period: one of patients with DVT or PE and another of individuals from the general population. Comparison cohorts (ten comparators per patient with splanchnic vein thrombosis) were matched on sex, age, and calendar year of diagnosis. We calculated absolute risks and used proportional hazard regression to calculate adjusted hazard ratios (HRs) for the primary outcomes of bleeding and arterial cardiovascular events after splanchnic vein thrombosis diagnosis (or the index date for comparison cohorts).

Findings: 1915 patients with splanchnic vein thrombosis, 18 373 patients with DVT or PE, and 19 150 individuals from the general population were included in the study. Patients with splanchnic vein thrombosis were followed up for a median of 1 year (IQR 0·1-3·9). These patients had a high risk of bleeding in the 30 days after diagnosis, both in absolute terms (4·3% [95% CI 3·5-5·3]) and in adjusted models (HR 9·64 [95% CI 6·46-14·40] vs DVT or PE; 39·79 [19·44-81·46] vs general population). Bleeding risk was still significantly increased in patients with splanchnic vein thrombosis up to 1 year after diagnosis (HR 3·01 [95% CI 2·28-3·97] vs DVT or PE; 6·83 [4·83-9·65] vs general population), and remained elevated for up to 10 years compared with patients with DVT or PE (1·93 [1·12-3·34]) and for up to 19 years compared with the general population (5·90 [2·22-15·64]). The risk of arterial cardiovascular events in patients with splanchnic vein thrombosis was high in the year after diagnosis (absolute risk 3·3% [95% CI 2·6-4·2] up to 30 days; 7·0% [5·8-8·4] up to 31-365 days), and in adjusted models was significantly higher than in patients with DVT or PE (HR 7·05 [95% CI 4·74-10·48] up to 30 days; 2·10 [1·62-2·72] up to 31-365 days) and individuals from the general population (15·75 [9·26-26·79] and 3·17 [2·34-4·27], respectively). However, this risk did not remain significantly elevated above that of patients with DVT or PE after 1 year or the general population after 5 years.

Interpretation: Patients with splanchnic vein thrombosis are at increased risk of adverse outcomes, particularly bleeding but also arterial cardiovascular events, for years after diagnosis compared with patients with DVT or PE and the general population. Physicians should be cognisant of these risks in patients with splanchnic vein thrombosis.

Funding: The Program for Clinical Research Infrastructure (PROCRIN), established by the Lundbeck Foundation and the Novo Nordisk Foundation.