Clinical outcome of patients with major bleeding after venous thromboembolism

José Antonio Nieto; Timoteo Camara; Elena Gonzalez-Higueras; Nuria Ruiz-Gimenez; Ricardo Guijarro; Pablo Javier Marchena; Manuel Monreal; for the RIETE Investigators

doi:10.1160/TH08-06-0390

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(05): 789-796
DOI: 10.1160/TH08-06-0390

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Clinical outcome of patients with major bleeding after venous thromboembolism

Findings from the RIETE Registry^[*]

José Antonio Nieto

¹Servicio de Medicina Interna, Hospital Virgen de la Luz, Cuenca, Spain

,

Timoteo Camara

¹Servicio de Medicina Interna, Hospital Virgen de la Luz, Cuenca, Spain

,

Elena Gonzalez-Higueras

¹Servicio de Medicina Interna, Hospital Virgen de la Luz, Cuenca, Spain

,

Nuria Ruiz-Gimenez

²Servicio de Medicina Interna, Hospital de la Princesa, Madrid, Spain

,

Ricardo Guijarro

³Servicio de Medicina Interna, Hospital Carlos Haya de Málaga, Spain

,

Pablo Javier Marchena

⁴Servicio de Medicina Interna, Hospital de Sant Boi (Barcelona), Spain

,

Manuel Monreal

⁵Professor of Medicine, Servicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

,

for the RIETE Investigators

› Author Affiliations

Abstract

Summary

The natural history of patients with venous thromboembolism (VTE) who develop a major bleeding complication while on anticoagulant therapy is not well known. RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. The clinical characteristics, treatment decisions and outcome of all VTE patients who had major bleeding during the first three months of anticoagulant therapy were retrospectively studied. As of January 2007, 17,368 patients were included in RIETE. Of these, 407 (2.3%) had major bleeding during the study period: 144 gastrointestinal, 119 haematoma, 51 intracranial, 43 genitourinary, 50 other. In 286 (69%) patients anticoagulant therapy was discontinued, in 74 (18%) not modified, in 38 (9.1%) a vena cava filter was inserted. During the first 30 days after bleeding, 24 (5.9%) patients re-bled, 20 (4.9%) had recurrent VTE, 133 (33%) died. Of these, 75 died of bleeding, 12 of recurrent pulmonary embolism. Most deaths occurred shortly after the bleeding episode (median:1 day).On multivariate analysis, insertion of a vena cava filter was the only variable independently associated with a lower incidence of fatal bleeding (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.01–0.79) and all-cause mortality (OR: 0.21; 95%CI: 0.07–0.63). In conclusion, the occurrence of major bleeding in patients with VTE is outstanding in terms of overall mortality (33% within 30 days), fatal bleeding (18%) or re-bleeding (5.9%). However, these patients also have an increased incidence of recurrent VTE (4.9%) and fatal pulmonary embolism (1.2%).

Keywords

Venous thromboembolism - major bleeding - anticoagulant therapy - outcome

Full Text

References

References
1 Kearon C, Kahn S, Agnelli G. et al. Antithrombotic therapy for venous thromboembolic disease. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8^th Edition). Chest 2008; 133: 454-545.
2 Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med 1989; 87: 144-152.
3 Kuijer PM, Hutten BA, Prins MH. et al. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159: 457-460.
4 Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139: 893-900.
5 Falgà C, Capdevila JA, Soler S. et al. for the RIETE Investigators. Clinical Outcome of Patients with Venous Thromboembolism and Renal Insufficiency. Findings from the RIETE Registry. Thromb Haemost 2007; 98: 771-776.
6 Blanco-Molina A, Trujillo-Santos J, Criado J. et al. and the RIETE Investigators. Venous Thrombo-embolism during pregnancy or postpartum: Findings from the RIETE Registry. Thromb Haemost 2007; 97: 186-190.
7 Arcelus JI, Monreal M, Caprini JA. et al. and the RIETE investigators. Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry. Thromb Haemost 2008; 99: 546-551.
8 Nieto JA, Bruscas MJ, Ruiz-Ribo D. et al. for the RIETE Investigators. Acute venous thromboembolism in patients with recent major bleeding. The influence of the site of bleeding and the time elapsed on outcome. J Thromb Haemost 2006; 04: 2367-2372.
9 Ruiz-Giménez N, Suárez C, González R. et al. and the RIETE Investigators. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100: 26-31.
10 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
11 Landefeld CS, Beyth R. Anticoagulation-related bleeding: Clinical epidemiology, prediction and prevention. Am J Med 1993; 95: 315-328.
12 Gitter MJ, Jaeger TM, Petterson TM. et al. Bleeding and thromboembolism during anticoagulant therapy: A population-based study in Rochester, Minnesota. Mayo Clin Proc 1995; 70: 725-733.
13 Van de Meer FJM, Rosendaal FR, Vandenbroucke JP. et al. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153: 1557-1562.
14 White RH, McKittrick T, Takakuwa J. et al. and the National Consortium of Anticoagulation Clinics. Management and prognosis of life-threatening bleeding during warfarin therapy. Arch Intern Med 1996; 156: 1197-1201.
15 Landefeld CS, Cook EF, Flatley M. et al. Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med 1987; 82: 703-713.
16 Landefeld CS, Rosenblatt MB, Goldman L. Bleeding in outpatients treated with warfarin: Relation to the prothrombin time and important remediable lesions. Am J Med 1989; 87: 153-159.
17 McMahan DA, Smith DM, Carey MA. et al. Risk of major hemorrhage for outpatients treated with warfarin. J Gen Intern Med 1998; 13: 311-316.
18 White RH, Beyth RJ, Zhou H. et al. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999; 107: 414-424.
19 Zidane M, Schram T, Planken EW. et al. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism. A Study in routine clinical practice. Arch Intern Med 2000; 160: 2369-2373.
20 Prandoni P, Lensing AWA, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-3488.
21 Bigaroni A, Perrier P, de Moerloose P. et al. Risk of major bleeding in unselected patients with venous thromboembolism. Blood Coag Fibrinol 2000; 11: 199-202.
22 Kucher N, Rossi E, de Rosa M. et al. Massive pulmonary embolism. Circulation 2006; 113: 577-582.
23 Decousus H, Leizorovicz A, Parent F. et al. A clinical trial of vena cava filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med 1998; 338: 409-415.