Journal of Thrombosis and Thrombolysis

, Volume 41, Issue 2, pp 312–320 | Cite as

Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism

  • F. A. Klok
  • C. Niemann
  • C. Dellas
  • G. Hasenfuß
  • S. Konstantinides
  • M. Lankeit


Bleeding-prediction scores may help guiding management of patients with pulmonary embolism (PE), although no such score has been validated. We aimed to externally validate and compare two bleeding-prediction scores for venous thromboembolism to three scores developed for patients with atrial fibrillation in a real-world cohort of PE patients. We performed a prospective observational cohort study in 448 consecutive PE patients who were treated with heparins followed by vitamin-K-antagonists. The Kuijer, RIETE, HEMORR2HAGES, HAS-BLED and ATRIA scores were assessed at baseline. All patients were followed for the occurrence of major bleeding over a 30-day period. The accuracies of both the overall, original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared, both for the 30-day period as well as for bleeding occurring in versus after the first week of treatment. 20 of 448 patients suffered major bleeding resulting in a cumulative incidence of 4.5 % (95 % CI 2.5–6.5). The predictive power of all five scores for bleeding was poor (c-statistics 0.57–0.64), both for the 3-level and 2-level score outcomes. No individual score was found to be superior. The HAS-BLED score had a good c-statistic for bleedings occurring after the first week of treatment (0.75, 95 % CI 0.47–1.0). Current available scoring systems have insufficient accuracy to predict overall anticoagulation-associated bleeding in patients treated for acute PE. To optimally target bleeding-prevention strategies, the development of a high quality PE-specific risk score is urgently needed.


Bleeding Pulmonary embolism Atrial fibrillation Risk score Prevention 



This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003). FAK was supported by the Niels Stensen fellowship. The authors are responsible for the contents of this publication.

Conflict of interest

FAK, GH, CD and CN have nothing to disclose. SK declares that he has received lecture fees and advisory board honoraria from Astra Zeneca, Bayer Health Care, Boehringer Ingelheim, Pfizer-Bristol-Myers Squibb and Daiichi Sankyo. ML reports receiving lecture fees and advisory board honoraria from Bayer Health Care and Pfizer-Bristol-Myers Squibb.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR (2012) Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141:e419S–e494SPubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk NA, Zamorano JL, Zompatori M (2014) 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC) Endorsed by the European Respiratory Society (ERS). Eur Heart J 35:3033–3069CrossRefPubMedGoogle Scholar
  3. 3.
    Linkins LA, Choi PT, Douketis JD (2003) Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 139:893–900CrossRefPubMedGoogle Scholar
  4. 4.
    Lecumberri R, Alfonso A, Jimenez D, Fernandez CC, Prandoni P, Wells PS, Vidal G, Barillari G, Monreal M (2013) Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism. Thromb Haemost 110:834–843CrossRefPubMedGoogle Scholar
  5. 5.
    Klok FA, Kooiman J, Huisman MV, Konstantinides S, Lankeit M (2015) Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review. Eur Respir J 45:201–210CrossRefPubMedGoogle Scholar
  6. 6.
    Kuijer PM, Hutten BA, Prins MH, Buller HR (1999) Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 159:457–460CrossRefPubMedGoogle Scholar
  7. 7.
    Ruiz-Gimenez N, Suarez C, Gonzalez R, Nieto JA, Todoli JA, Samperiz AL, Monreal M (2008) Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 100:26–31PubMedGoogle Scholar
  8. 8.
    Fang MC, Go AS, Chang Y, Borowsky LH, Pomernacki NK, Udaltsova N, Singer DE (2011) A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 58:395–401PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY (2010) 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 138:1093–1100CrossRefPubMedGoogle Scholar
  10. 10.
    Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW, Radford MJ (2006) Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 151:713–719CrossRefPubMedGoogle Scholar
  11. 11.
    Wann LS, Curtis AB, Ellenbogen KA, Estes NA, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le HJ, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS (2013) Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 127:1916–1926CrossRefPubMedGoogle Scholar
  12. 12.
    Lankeit M, Friesen D, Aschoff J, Dellas C, Hasenfuss G, Katus H, Konstantinides S, Giannitsis E (2010) Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J 31:1836–1844CrossRefPubMedGoogle Scholar
  13. 13.
    Dellas C, Puls M, Lankeit M, Schafer K, Cuny M, Berner M, Hasenfuss G, Konstantinides S (2010) Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensive patients with acute pulmonary embolism. J Am Coll Cardiol 55:2150–2157CrossRefPubMedGoogle Scholar
  14. 14.
    Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV (2014) Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 370:1402–1411CrossRefPubMedGoogle Scholar
  15. 15.
    Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808CrossRefPubMedGoogle Scholar
  16. 16.
    Schulman S, Kearon C (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694CrossRefPubMedGoogle Scholar
  17. 17.
    Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36CrossRefPubMedGoogle Scholar
  18. 18.
    Scherz N, Mean M, Limacher A, Righini M, Jaeger K, Beer HJ, Frauchiger B, Osterwalder J, Kucher N, Matter CM, Banyai M, Angelillo-Scherrer A, Lammle B, Husmann M, Egloff M, Aschwanden M, Bounameaux H, Cornuz J, Rodondi N, Aujesky D (2013) Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism. J Thromb Haemost 11:435–443CrossRefPubMedGoogle Scholar
  19. 19.
    Donze J, Rodondi N, Waeber G, Monney P, Cornuz J, Aujesky D (2012) Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study. Am J Med 125:1095–1102CrossRefPubMedGoogle Scholar
  20. 20.
    Riva N, Bellesini M, Di Minno MN, Mumoli N, Pomero F, Franchini M, Fantoni C, Lupoli R, Brondi B, Borretta V, Bonfanti C, Ageno W, Dentali F (2014) Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study. Thromb Haemost 112:511–521CrossRefPubMedGoogle Scholar
  21. 21.
    Kooiman J, van Hagen N, Iglesias Del Sol A, Planken EV, Lip GY, van der Meer FJ, Cannegieter SC, Klok FA, Huisman MV (2015) The HAS-BLED score identifies patients with acute venous thromboembolism at high risk of major bleeding complications during the first six months of anticoagulant treatment. PLoS ONE 10:e0122520PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Piovella C, Dalla VF, Trujillo-Santos J, Pesavento R, Lopez L, Font L, Valle R, Nauffal D, Monreal M, Prandoni P (2014) Comparison of four scores to predict major bleeding in patients receiving anticoagulation for venous thromboembolism: findings from the RIETE registry. Intern Emerg Med 9:847–852CrossRefPubMedGoogle Scholar
  23. 23.
    Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van NP, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M (2003) Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 349:631–639Google Scholar
  24. 24.
    Matchar DB, Samsa GP, Cohen SJ, Oddone EZ, Jurgelski AE (2002) Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the managing anticoagulation services trial. Am J Med 113:42–51CrossRefPubMedGoogle Scholar
  25. 25.
    Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER III, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA III, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH (2013) A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med 369:2283–2293PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV (2014) Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 12:320–328CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • F. A. Klok
    • 1
  • C. Niemann
    • 2
  • C. Dellas
    • 3
  • G. Hasenfuß
    • 2
  • S. Konstantinides
    • 1
  • M. Lankeit
    • 1
    • 2
  1. 1.Center for Thrombosis and Hemostasis (CTH), University Medical Center MainzJohannes Gutenberg University of MainzMainzGermany
  2. 2.Clinic for Cardiology and Pulmonology, Heart CenterUniversity of GöttingenGöttingenGermany
  3. 3.Department of Paediatric Cardiology, Heart CenterUniversity of GöttingenGöttingenGermany

Personalised recommendations