Thromb Haemost 2014; 112(03): 511-521
DOI: 10.1160/TH14-01-0081
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism

A multicentre retrospective cohort study
Nicoletta Riva
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Marta Bellesini
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Matteo Nicola Dario Di Minno
2   Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
,
Nicola Mumoli
3   Department of Internal Medicine, Ospedale Civile Livorno, Livorno, Italy
,
Fulvio Pomero
4   Department of Internal Medicine, ‘S. Croce e Carle’ Hospital, Cuneo, Italy
,
Massimo Franchini
5   Department of Transfusion Medicine and Haematology, Carlo Poma Hospital, Mantua, Italy
,
Chiara Fantoni
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Roberta Lupoli
2   Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
,
Barbara Brondi
3   Department of Internal Medicine, Ospedale Civile Livorno, Livorno, Italy
,
Valentina Borretta
4   Department of Internal Medicine, ‘S. Croce e Carle’ Hospital, Cuneo, Italy
,
Carlo Bonfanti
5   Department of Transfusion Medicine and Haematology, Carlo Poma Hospital, Mantua, Italy
,
Walter Ageno
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Francesco Dentali
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
› Author Affiliations
Further Information

Publication History

Received: 25 January 2014

Accepted after major revision: 11 April 2014

Publication Date:
20 November 2017 (online)

Summary

Bleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. We retrospectively included adult patients on vitamin K antagonists for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (± 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive value for bleeding complications during the first three months of treatment (area under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59–0.78), while only the ACCP score showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51–0.72). These two scores had also the highest sensitivity and the highest negative predictive value. None of the scores predicted MB better than chance. Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.

 
  • References

  • 1 Wiedermann CJ, Stockner I. Warfarin-induced bleeding complications - clinical presentation and therapeutic options. Thromb Res 2008; 122 (Suppl. 02) S13-18.
  • 2 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.
  • 3 Kearon C, Akl EA, Comerota AJ. et al. American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (02) Suppl e419S-94S Erratum in: Chest. 2012; 142: 1698-1704.
  • 4 Shireman TI, Mahnken JD, Howard PA. et al. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest 2006; 130: 1390-1396.
  • 5 Gage BF, Yan Y, Milligan PE. et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-719.
  • 6 Pisters R, Lane DA, Nieuwlaat R. et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093-1100.
  • 7 Fang MC, Go AS, Chang Y. et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58: 395-401.
  • 8 Poli D, Antonucci E, Testa S. et al. Italian Federation of Anticoagulation Clinics. Bleeding risk in very old patients on vitamin K antagonist treatment: results of a prospective collaborative study on elderly patients followed by Italian Centres for Anticoagulation. Circulation 2011; 124: 824-829.
  • 9 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.
  • 10 Ruíz-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.
  • 11 von Elm E, Altman DG, Egger M. et al. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007; Oct 16 147 (08) 573-7. Erratum in: Ann Intern Med 2008; 148: 168.
  • 12 Rosendaal FR, Cannegieter SC, van der Meer FJ. et al. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-239.
  • 13 Schulman S, Kearon C. on behalf of the Subcommittee on Control of Anticoagulation of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
  • 14 Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
  • 15 Charlson ME, Pompei P, Ales KL. et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-383.
  • 16 Janssen KJ, Vergouwe Y, Donders AR, Harrell Jr, FE, Chen Q, Grobbee DE, Moons KG. Dealing with missing predictor values when applying clinical prediction models. Clin Chem 2009; 55: 994-1001.
  • 17 Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143: 29-36.
  • 18 Cleves MA. From the help desk: Comparing areas under receiver operating characteristic curves from two or more probit or logit models. Stata J 2002; 2: 301-313.
  • 19 Levey AS, Coresh J, Greene T. et al. Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247-254.
  • 20 Lip GY, Andreotti F, Fauchier L. et al. European Heart Rhythm Association. Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb Haemost 2011; 106: 997-1011.
  • 21 Prandoni P, Lensing AW, 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.
  • 22 Apostolakis S, Lane DA, Guo Y. et al. Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. J Am Coll Cardiol 2012; 60: 861-867.
  • 23 Apostolakis S, Lane DA, Guo Y. et al. Performance of the HEMORR 2HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in nonwarfarin anticoagulated atrial fibrillation patients. J Am Coll Cardiol 2013; 61: 386-387.
  • 24 Poli D, Antonucci E, Testa S. et al. FCSA (Italian Federation of Anticoagulation Clinics). The predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective collaborative EPICA study. J Thromb Haemost 2013; 11: 1053-1058.
  • 25 Scherz N, Méan M, Limacher A. et al. Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism. J Thromb Haemost 2013; 11: 435-443.
  • 26 De Caterina R, Husted S, Wallentin L. et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease. Thromb Haemost 2013; 110: 1087-1107.
  • 27 Apostolakis S, Lane DA, Buller H. et al. Comparison of the CHADS2, CHA2DS2-VASc and HAS-BLED scores for the prediction of clinically relevant bleeding in anticoagulated patients with atrial fibrillation: the AMADEUS trial. Thromb Haemost 2013; 110: 1074-1079.
  • 28 van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153: 1557-1562.
  • 29 Gallego P, Roldan V, Marín F. et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost 2013; 110: 1189-1198.
  • 30 Palareti G, Legnani C, Cosmi B. et al. Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence. J Thromb Haemost 2005; 03: 955-961.