Clinical Outcome of Patients with Venous Thromboembolism and Recent Major Bleeding: Findings from a Prospective Registry (RIETE).
Authors: Monreal Manuel , Nieto José , de Tuesta Ana , Marchena Pablo , Tiberio Gregorio , Todoli José , Samperiz Angel ,   the RIETE Investigators
Published: October 2019

Abstract
Introduction Patients who have experienced a recent major bleeding episode are usually excluded from clinical trials of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials of VTE treatment may not be optimal for these patients. The Registro Informatizado de la Enfermedad TromboEmbólica (RIETE), initiated in March 2001, is a multicenter, observational registry gathering data on VTE treatment practices and clinical outcomes in patients with objectively confirmed, symptomatic, acute VTE. The aim of this analysis was to study outcomes in patients with VTE who had experienced major bleeding <30 days prior to VTE diagnosis.
Methods Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patients are excluded if they are participating in a therapeutic clinical trial or not available for 3-months follow-up. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3-months are recorded.
Results Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding prior to VTE diagnosis: 69 (40.6%) gastrointestinal tract; 60 (35.3%) intracranial; 41 (24.1%) other. More patients with recent major bleeding had cancer compared with those without recent major bleeding (26.4% vs 20.4%, respectively; p=0.05). More patients who experienced recent major bleeding had undergone surgery <2 months prior to enrollment or had immobility ≥4 days. The incidences of recurrent PE and minor, major, and fatal bleeding complications were also higher in patients who had experienced recent major bleeding (table 1). Patients with recent major bleeding and cancer had an increased incidence of major bleeding compared to those without cancer (20.0% vs. 2.4%, respectively; OR 10.0; 95% CI 2.3–50.0; p<0.001); 11.0% of patients who had recent major bleeding prior to VTE diagnosis and cancer experienced fatal PE compared with none in patients who had recent major bleeding but without cancer (OR 4.1; 95% CI 4.98–17; p<0.05).
Conclusion Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes, in terms of bleeding complications, fatal PE and overall mortality compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to VTE diagnosis, those with cancer had a poorer clinical outcome than those without cancer.
Table 1. Clinical outcome of enrolled patients
3-month outcome Recent major bleeding No recent major bleeding OR (95% CI) p value n (%) n=170 n=6191 Fatal bleeding 7 (4.1) 41 (0.6) 6.4 (2.6-15) <0.001 Major bleeding 12 (7.1) 146 (2.3) 3.1 (1.6-5.9) 0.001 Minor bleeding 12 (7.1) 172 (2.8) 2.6 (1.4-5.0) <0.005 Fatal (initial) PE 1 (0.6) 14 (0.2) 2.6 (0.2-19) NS Fatal (recurrent) PE 4 (2.4) 33 (0.5) 4.5 (1.3-14) <0.05 Recurrent VTE 8 (4.7) 184 (2.9) 1.6 (0.7-3.4) NS Overall mortality 25 (15.0) 479 (7.7) 2.1 (1.3-3.2) <0.005