Periprocedural bleeding in patients undergoing percutaneous coronary intervention
- Paul Sorajja, MD
Paul Sorajja, MD
- Associate Professor of Medicine
- Minneapolis Heart Institute
- David R Holmes, Jr, MD
David R Holmes, Jr, MD
- Professor of Medicine
- Mayo Clinic College of Medicine
The advent of aggressive, multidrug antithrombotic therapy during percutaneous coronary intervention (PCI) has led to significant reductions in short- and long-term ischemic outcomes. (See "Antithrombotic therapy for elective percutaneous coronary intervention: General use".)
However, periprocedural bleeding is a frequent complication of PCI, and its frequency and severity is related in part to the intensity of antithrombotic therapy. Initially, periprocedural bleeding was viewed as a relatively benign consequence, but data have linked the occurrence of bleeding and its treatment (ie, blood transfusion) to increased short- and long-term mortality.
This topic reviews most aspects of periprocedural bleeding among patients undergoing PCI. Gastrointestinal bleeding in this setting is discussed separately. (See "Periprocedural and long-term gastrointestinal bleeding in patients undergoing percutaneous coronary intervention".)
Bleeding in relation to coronary artery bypass grafting or in association with diagnostic coronary angiography is discussed elsewhere. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Bleeding' and "Complications of diagnostic cardiac catheterization", section on 'Local vascular complications'.)
For the purpose of this topic, periprocedural bleeding is any bleeding that occurs during or within 48 hours of the procedure. However, some studies have including episodes of bleeding that occur during the index hospitalization. Estimates of the incidence of periprocedural bleeding during percutaneous coronary intervention (PCI) lack precision due to the use of different definitions. (See 'Incidence' below.) In addition, relevant data come from differing patient populations who were treated with varying regimens of adjunctive pharmacology. Early studies of adjunctive pharmacology in PCI utilized definitions that were extrapolated from fibrinolytic trials (such as the TIMI and GUSTO scales). These early definitions focused on occurrence of intracranial bleeds or large drops in hemoglobin . In more studies, the definitions of major bleeding have been more inclusive of less severe, but clinically significant, bleeds (table 1 and table 2). These definitions of major bleeding have included events such as the need for transfusion, bleeding requiring surgical intervention or prolonging hospital stay, or cardiac tamponade.
- Rao AK, Pratt C, Berke A, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial--phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11:1.
- Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123:2736.
- Ndrepepa G, Schuster T, Hadamitzky M, et al. Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention. Circulation 2012; 125:1424.
- Vranckx P, Leonardi S, Tebaldi M, et al. Prospective validation of the Bleeding Academic Research Consortium classification in the all-comer PRODIGY trial. Eur Heart J 2014; 35:2524.
- Kikkert WJ, van Geloven N, van der Laan MH, et al. The prognostic value of bleeding academic research consortium (BARC)-defined bleeding complications in ST-segment elevation myocardial infarction: a comparison with the TIMI (Thrombolysis In Myocardial Infarction), GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries), and ISTH (International Society on Thrombosis and Haemostasis) bleeding classifications. J Am Coll Cardiol 2014; 63:1866.
- Feit F, Voeltz MD, Attubato MJ, et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 Trial. Am J Cardiol 2007; 100:1364.
- Kinnaird TD, Stabile E, Mintz GS, et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. Am J Cardiol 2003; 92:930.
- Doyle BJ, Ting HH, Bell MR, et al. Major femoral bleeding complications after percutaneous coronary intervention: incidence, predictors, and impact on long-term survival among 17,901 patients treated at the Mayo Clinic from 1994 to 2005. JACC Cardiovasc Interv 2008; 1:202.
- Chhatriwalla AK, Amin AP, Kennedy KF, et al. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. JAMA 2013; 309:1022.
- Marso SP, Amin AP, House JA, et al. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA 2010; 303:2156.
- Jolly SS, Yusuf S, Cairns J, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet 2011; 377:1409.
- Baklanov DV, Kim S, Marso SP, et al. Comparison of bivalirudin and radial access across a spectrum of preprocedural risk of bleeding in percutaneous coronary intervention: analysis from the national cardiovascular data registry. Circ Cardiovasc Interv 2013; 6:347.
- Nikolsky E, Mehran R, Dangas G, et al. Development and validation of a prognostic risk score for major bleeding in patients undergoing percutaneous coronary intervention via the femoral approach. Eur Heart J 2007; 28:1936.
- Iijima R, Ndrepepa G, Mehilli J, et al. Profile of bleeding and ischaemic complications with bivalirudin and unfractionated heparin after percutaneous coronary intervention. Eur Heart J 2009; 30:290.
- Rao SV, Dai D, Subherwal S, et al. Association between periprocedural bleeding and long-term outcomes following percutaneous coronary intervention in older patients. JACC Cardiovasc Interv 2012; 5:958.
- Steg PG, Huber K, Andreotti F, et al. Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2011; 32:1854.
- Fernandes LS, Tcheng JE, O'Shea JC, et al. Is glycoprotein IIb/IIIa antagonism as effective in women as in men following percutaneous coronary intervention?. Lessons from the ESPRIT study. J Am Coll Cardiol 2002; 40:1085.
- Chacko M, Lincoff AM, Wolski KE, et al. Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: a subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial. Am Heart J 2006; 151:1032.e1.
- Hochholzer W, Wiviott SD, Antman EM, et al. Predictors of bleeding and time dependence of association of bleeding with mortality: insights from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). Circulation 2011; 123:2681.
- Lip GY, Huber K, Andreotti F, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Thromb Haemost 2010; 103:13.
- Mehran R, Pocock S, Nikolsky E, et al. Impact of bleeding on mortality after percutaneous coronary intervention results from a patient-level pooled analysis of the REPLACE-2 (randomized evaluation of PCI linking angiomax to reduced clinical events), ACUITY (acute catheterization and urgent intervention triage strategy), and HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trials. JACC Cardiovasc Interv 2011; 4:654.
- Kastrati A, Mehilli J, Schühlen H, et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004; 350:232.
- Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004; 292:45.
- Montalescot G, White HD, Gallo R, et al. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006; 355:1006.
- Bhatt DL, Lee BI, Casterella PJ, et al. Safety of concomitant therapy with eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: results of the Coronary Revascularization Using Integrilin and Single bolus Enoxaparin Study. J Am Coll Cardiol 2003; 41:20.
- Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006; 354:1464.
- Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289:853.
- Kastrati A, Neumann FJ, Mehilli J, et al. Bivalirudin versus unfractionated heparin during percutaneous coronary intervention. N Engl J Med 2008; 359:688.
- Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357:2001.
- Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361:1045.
- Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009; 361:2318.
- Bhatt DL. Prasugrel in clinical practice. N Engl J Med 2009; 361:940.
- Suh JW, Mehran R, Claessen BE, et al. Impact of in-hospital major bleeding on late clinical outcomes after primary percutaneous coronary intervention in acute myocardial infarction the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol 2011; 58:1750.
- Mamas MA, Anderson SG, Carr M, et al. Baseline bleeding risk and arterial access site practice in relation to procedural outcomes after percutaneous coronary intervention. J Am Coll Cardiol 2014; 64:1554.
- Ndrepepa G, Berger PB, Mehilli J, et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008; 51:690.
- Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol 2007; 49:1362.
- Mehran R, Pocock SJ, Nikolsky E, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010; 55:2556.
- Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008; 358:1229.
- Jani SM, Smith DE, Share D, et al. Blood transfusion and in-hospital outcomes in anemic patients with myocardial infarction undergoing percutaneous coronary intervention. Clin Cardiol 2007; 30:II49.
- Yatskar L, Selzer F, Feit F, et al. Access site hematoma requiring blood transfusion predicts mortality in patients undergoing percutaneous coronary intervention: data from the National Heart, Lung, and Blood Institute Dynamic Registry. Catheter Cardiovasc Interv 2007; 69:961.
- Kim P, Dixon S, Eisenbrey AB, et al. Impact of acute blood loss anemia and red blood cell transfusion on mortality after percutaneous coronary intervention. Clin Cardiol 2007; 30:II35.
- Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358:2218.
- Spencer FA, Moscucci M, Granger CB, et al. Does comorbidity account for the excess mortality in patients with major bleeding in acute myocardial infarction? Circulation 2007; 116:2793.
- Doyle BJ, Rihal CS, Gastineau DA, Holmes DR Jr. Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol 2009; 53:2019.
- Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood 2005; 106:2605.
- Taylor JE, Henderson IS, Stewart WK, Belch JJ. Erythropoietin and spontaneous platelet aggregation in haemodialysis patients. Lancet 1991; 338:1361.
- Smith KJ, Bleyer AJ, Little WC, Sane DC. The cardiovascular effects of erythropoietin. Cardiovasc Res 2003; 59:538.
- Louvard Y, Benamer H, Garot P, et al. Comparison of transradial and transfemoral approaches for coronary angiography and angioplasty in octogenarians (the OCTOPLUS study). Am J Cardiol 2004; 94:1177.
- Pristipino C, Trani C, Nazzaro MS, et al. Major improvement of percutaneous cardiovascular procedure outcomes with radial artery catheterisation: results from the PREVAIL study. Heart 2009; 95:476.
- Koreny M, Riedmüller E, Nikfardjam M, et al. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis. JAMA 2004; 291:350.
- Ellis SG, Bhatt D, Kapadia S, et al. Correlates and outcomes of retroperitoneal hemorrhage complicating percutaneous coronary intervention. Catheter Cardiovasc Interv 2006; 67:541.
- Ducas J, Chan MC, Miller A, Kashour T. Immediate protamine administration and sheath removal following percutaneous coronary intervention: a prospective study of 429 patients. Catheter Cardiovasc Interv 2002; 56:196.
- Cosgrave J, Qasim A, Latib A, et al. Protamine usage following implantation of drug-eluting stents: a word of caution. Catheter Cardiovasc Interv 2008; 71:913.
- Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol 2007; 49:734.
- Briguori C, Di Mario C, De Gregorio J, et al. Administration of protamine after coronary stent deployment. Am Heart J 1999; 138:64.
- Sherwood MW, Wang Y, Curtis JP, et al. Patterns and outcomes of red blood cell transfusion in patients undergoing percutaneous coronary intervention. JAMA 2014; 311:836.
- Chase AJ, Fretz EB, Warburton WP, et al. Association of the arterial access site at angioplasty with transfusion and mortality: the M.O.R.T.A.L study (Mortality benefit Of Reduced Transfusion after percutaneous coronary intervention via the Arm or Leg). Heart 2008; 94:1019.
- Welch HG, Meehan KR, Goodnough LT. Prudent strategies for elective red blood cell transfusion. Ann Intern Med 1992; 116:393.
- Almac E, Ince C. The impact of storage on red cell function in blood transfusion. Best Pract Res Clin Anaesthesiol 2007; 21:195.
- Anniss AM, Sparrow RL. Variable adhesion of different red blood cell products to activated vascular endothelium under flow conditions. Am J Hematol 2007; 82:439.
- Berezina TL, Zaets SB, Morgan C, et al. Influence of storage on red blood cell rheological properties. J Surg Res 2002; 102:6.
- Allen BW, Piantadosi CA. How do red blood cells cause hypoxic vasodilation? The SNO-hemoglobin paradigm. Am J Physiol Heart Circ Physiol 2006; 291:H1507.
- Twomley KM, Rao SV, Becker RC. Proinflammatory, immunomodulating, and prothrombotic properties of anemia and red blood cell transfusions. J Thromb Thrombolysis 2006; 21:167.
- Janatpour K, Holland PV. Noninfectious serious hazards of transfusion. Curr Hematol Rep 2002; 1:149.
- Wu WC, Rathore SS, Wang Y, et al. Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 2001; 345:1230.
- Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999; 340:409.
- Hébert PC, Yetisir E, Martin C, et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Crit Care Med 2001; 29:227.
- Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004; 292:1555.
- RISK FACTORS
- Antithrombotic therapy
- OUTCOMES AFTER BLEEDING
- Access site
- Gastrointestinal tract
- Activated clotting time
- Patients on oral anticoagulants
- CLINICAL MANIFESTATIONS AND DIAGNOSIS
- Femoral artery
- Retroperitoneal space
- Gastrointestinal tract
- Cranial bleeding
- Reversal of anticoagulation
- Reversal of GPIIb/IIIa inhibitors
- Blood transfusion
- - Potential mechanisms of adverse outcome after blood cell transfusion
- - Recommendations for blood transfusion
- SUMMARY AND RECOMMENDATIONS