Acute venous thromboembolism in patients with recent major bleeding. The influence of the site of bleeding and the time elapsed on outcome

Background: Patients with major bleeding who subsequently develop clinically apparent venous thromboembolism (VTE) present a particularly difficult therapeutic dilemma. Methods: RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We retrospectively studied those who had experienced recent major bleeding (< 30 days prior to VTE) to assess the influence of the site of bleeding and the time elapsed to VTE on their 3 month outcome. Results: Of 12 294 patients enrolled up to July 2005, 306 (2.5%) had recent major bleeding: gastrointestinal (GI) tract, 116 (38%); intracranial, 94 (31%); other, 96 (31%). During the study period, 19 patients [6.2%; 95% confidence interval (CI) 3.5-8.9] with recent bleeding rebled (eight died): 13 of them (68%) during the first 2 weeks. Multivariate analysis confirmed that patients with recent GI bleeding had an increased risk for both major rebleeding (hazard ratio 2.8; 95% CI 1.4-5.3) and death (hazard ratio 1.9; 95% CI 1.2-3.1) compared to those with no recent bleeding. Those who bled in other sites had an increased risk only for death (hazard ratio 2.0; 95% CI 1.2-3.3). An elapsed time of < 2 weeks from bleeding to the index VTE event was also associated with an increased risk for major rebleeding (hazard ratio 2.4; 95% CI 1.2-5.0) and death (hazard ratio 2.8; 95% CI 1.8-4.5). Conclusion: The incidence of new bleeding or death depends on the site of prior bleeding and the time elapsed until VTE. This information may help to identify the best therapeutic approach for these high-risk patients.