Major bleedings in mechanical prosthetic heart valves patients on Vitamin K antagonist treatment. Data from the PLECTRUM Study


Published: 27 July 2022
Abstract Views: 3057
PDF: 98
Supplementary Files: 15
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

  • Daniela Poli Center of Atherothrombotic Disease, Careggi University Hospital, Firenze, Italy.
  • Emilia Antonucci Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Gualtiero Palareti Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Roberto Facchinetti Test Lab, Ospedale Civile Maggiore Integrated University Hospital, Borgo Trento, Italy.
  • Pietro Falco Medical Pontino Specialist Outpatient Clinic, Latina, Italy.
  • Giuseppina Serricchio Test Lab, Sant'Anna Hospital, San Fermo della Battaglia, & Lariana Local Health Unit, Como, Italy.
  • Teresa Lerede Thrombosis and Hemostasis Center, Immunohematology and Transfusion Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy.
  • Lucilla Masciocco Department of Internal Medicine, Lastaria Hospital, Lucera, Italy.
  • Paolo Gresele Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Italy.
  • Sophie Testa Haemostasis and Thrombosis Centre, Cremona Local Health Unit, Cremona, Italy.

Patients with mechanical prosthetic heart valves (MHV) need vitamin K antagonist (VKA) treatment, due to the high thrombotic risk. The need to evaluate the bleeding risk of these patients is of great clinical relevance. This is an observational retrospective multicenter study among Centers affiliated to the Italian Federation of Anticoagulation Clinics on MHV patients, with the aim to evaluate the risk of major bleeding (MB) and associated risk factors. 2357 patients with MHV were included in the study, patients were followed for 24.081 pt-years; 246 patients had MB (rate 1.0 ×100 pt-yrs), 54 were intracranial hemorrhage (rate 0.22 ×100 pt-yrs). Patients with MB were significantly older, more affected by peripheral obstructive arterial disease (POAD) and atrial fibrillation (AF), and presented a history of previous MB, with respect to patients who did not bleed. Patients with MB showed a trend for lower time in therapeutic range (TTR), and a significant number of patients had a TTR in the lower quartile. Patients with MB had a higher mortality rate with respect to patients who did not bleed (p=0.001). The history of previous bleeding, the presence of POAD or of AF, and a TTR in the lowest quartile, were significantly associated with MB. MHV patients treated with VKAs followed by Anticoagulation Clinics, showed a low bleeding risk. Risk factors associated with major bleeding are older age, the presence of POAD or AF, the history of previous bleeding, and poor quality of anticoagulation. Patients who experienced MB during anticoagulation are at high risk of death.


Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451-96. DOI: https://doi.org/10.1093/eurheartj/ehs109

Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and Thrombolytic Therapy for Valvular Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e576S-600S. DOI: https://doi.org/10.1378/chest.11-2305

Chiang YP, Chikwe J, Moskowitz AJ, et al. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years. JAMA 2014;312:1323-9. DOI: https://doi.org/10.1001/jama.2014.12679

Head SJ, Celik M, Kappetein AP. Mechanical versus bioprosthetic aortic valve replacement. Eur Heart J 2017;38:2183-91. DOI: https://doi.org/10.1093/eurheartj/ehx141

Goldstone AB, Chiu P, Baiocchi M, et al. Mechanical or Biologic Prostheses for Aortic-Valve and Mitral-Valve Replacement. N Engl J Med 2017;377:1847-57. DOI: https://doi.org/10.1056/NEJMoa1613792

Zhao DF, Seco M, Wu JJ, et al. Mechanical Versus Bioprosthetic Aortic Valve Replacement in Middle-Aged Adults: A Systematic Review and Meta-Analysis. Ann Thorac Surg 2016;102:315-27. DOI: https://doi.org/10.1016/j.athoracsur.2015.10.092

Watkins DA, Johnson CO, Colquhoun SM, et al. Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015. N Engl J Med 2017;377:713-22. DOI: https://doi.org/10.1056/NEJMoa1603693

Eikelboom JW, Brueckmann M, Van de Werf F. Dabigatran in patients with mechanical heart valves. N Engl J Med 2014;370:383-4. DOI: https://doi.org/10.1056/NEJMc1315004

Poli D, Antonucci E, Pengo V, et al. Mechanical prosthetic heart valves: Quality of anticoagulation and thromboembolic risk. The observational multicenter PLECTRUM study. Int J Cardiol 2018;267:68-73. DOI: https://doi.org/10.1016/j.ijcard.2018.04.042

Antonucci E, Poli D, Tosetto A, et al. The Italian START-Register on Anticoagulation with Focus on Atrial Fibrillation. PLoS One 2015;10:e0124719. DOI: https://doi.org/10.1371/journal.pone.0124719

Tripodi A, Chantarangkul V, Akkawat B, et al. A partial factor v deficiency in anticoagulated lyophilized plasmas has been identified as a cause of the international normalized ratio discrepancy in the external quality assessment scheme. Thromb Res 1995;78:283-92. DOI: https://doi.org/10.1016/0049-3848(95)00061-U

Palareti G, Leali N, Coccheri S, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 1996;348:423-8. DOI: https://doi.org/10.1016/S0140-6736(96)01109-9

Rosendaal FR, Cannegieter SC, Vandermeer FJM, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993;69:236-7. DOI: https://doi.org/10.1055/s-0038-1651587

Hering D, Piper C, Bergemann R, et al. Thromboembolic and bleeding complications following St. Jude Medical valve replacement: results of the German Experience With Low-Intensity Anticoagulation Study. Chest 2005;127:53-9. DOI: https://doi.org/10.1378/chest.127.1.53

Torella M, Torella D, Chiodini P, et al. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial. Am Heart J 2010;160:171-8. DOI: https://doi.org/10.1016/j.ahj.2010.05.005

Labaf A, Svensson PJ, Renlund H, et al. Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis: A nationwide population-based study. Am Heart J 2016;181:1-9. DOI: https://doi.org/10.1016/j.ahj.2016.06.026

Grzymala-Lubanski B, Labaf A, Englund E, et al. Mechanical heart valve prosthesis and warfarin - treatment quality and prognosis. Thromb Res 2014;133:795-8. DOI: https://doi.org/10.1016/j.thromres.2014.02.031

Poli D, Antonucci E, Testa S, et al. 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;124:824-9. DOI: https://doi.org/10.1161/CIRCULATIONAHA.110.007864

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;138:1093-100. DOI: https://doi.org/10.1378/chest.10-0134

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;105:91-9. DOI: https://doi.org/10.1016/S0002-9343(98)00198-3

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. DOI: https://doi.org/10.1016/j.jacc.2011.03.031

Kirchhof P, Benussi S, Kotecha D, et al. [2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS]. Kardiol Pol 2016;74:1359-469. DOI: https://doi.org/10.5603/KP.2016.0172

Kershenbaum A, Lavi I, Rennert G, Almog R. Fecal occult blood test performance indicators in warfarin-treated patients. Dis Colon Rectum 2010;53:224-9. DOI: https://doi.org/10.1007/DCR.0b013e3181b9d89e

Barada K, Abdul-Baki H, El H II, et al. Gastrointestinal bleeding in the setting of anticoagulation and antiplatelet therapy. J Clin Gastroenterol 2009;43:5-12. DOI: https://doi.org/10.1097/MCG.0b013e31811edd13

Warfarin Antiplatelet Vascular Evaluation Trial I, Anand S, Yusuf S, et al. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 2007;357:217-27. DOI: https://doi.org/10.1056/NEJMoa065959

Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017;135:e726-79. DOI: https://doi.org/10.1161/CIR.0000000000000502

Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e44S-e88S. DOI: https://doi.org/10.1378/chest.11-2292

Poli D, Antonucci E, Pengo V, et al. Risk of reoperation in bioprosthetic valve patients with indication for long-term anticoagulation. Results from the observational retrospective multicentre PLECTRUM study. Open Heart 2018;5:e000837. DOI: https://doi.org/10.1136/openhrt-2018-000837

Poli, D., Antonucci, E., Palareti, G., Facchinetti, R., Falco, P., Serricchio, G., Lerede, T., Masciocco, L., Gresele, P., & Testa, S. (2022). Major bleedings in mechanical prosthetic heart valves patients on Vitamin K antagonist treatment. Data from the PLECTRUM Study. Bleeding, Thrombosis, and Vascular Biology, 1(2). https://doi.org/10.4081/btvb.2022.34

Downloads

Download data is not yet available.

Citations