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Bleeding with antiplatelet agents

Bleeding with antiplatelet agents. Giuseppe Biondi-Zoccai , MD Sapienza University of Rome , Italy giuseppe.biondizoccai@uniroma1.it. Learning goals. Scope of the problem Definitions Pragmatic approach to bleeding Specific recommendations. Learning goals. Scope of the problem

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Bleeding with antiplatelet agents

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  1. Bleeding with antiplatelet agents Giuseppe Biondi-Zoccai, MD Sapienza University ofRome, Italy giuseppe.biondizoccai@uniroma1.it

  2. Learninggoals • Scope of the problem • Definitions • Pragmaticapproachtobleeding • Specificrecommendations

  3. Learninggoals • Scope of the problem • Definitions • Pragmaticapproachtobleeding • Specificrecommendations

  4. Coagulation

  5. Platelets PAR inhibitors Anticoagulants <- <- Aspirin <- P2Y12 inhibitors <- <- IIb/IIIa inhibitors Jackson et al, NatRevDrugDiscov 2003

  6. Bleedingiscommond and kills, irrespectiveofdefinition Mehranet al, Circulation 2011

  7. Bleedingkillsafter PCI Chhatriwallaet al, JAMA 2013

  8. GI bleedingkills in the ICU Cook et al, Crit Care 2001

  9. Learninggoals • Scope of the problem • Definitions • Pragmaticapproachtobleeding • Specificrecommendations

  10. Historicaldefinition: TIMI Mehranet al, Circulation 2011

  11. New-entries: GUSTO, CURE, ACUITY, HORIZONS Mehranet al, Circulation 2011

  12. BleedingAcademicResearchConsortium Type 0: no bleeding Type 1: bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-discontinuation of medical therapy Type 2: any overt, actionable sign of hemorrhage (eg, more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for type 3, 4, or 5, but does meet at least one of the following criteria: (1) requiring nonsurgical, medical intervention by a healthcare professional, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation Mehranet al, Circulation 2011

  13. BleedingAcademicResearchConsortium Type 3a: Overt bleeding plus hemoglobin drop of 3 to 5 g/dL* (provided hemoglobin drop is related to bleed), or any transfusion with overt bleeding Type 3b: Overtbleeding plus hemoglobindrop 5 g/dL* (providedhemoglobindrop is related to bleed), cardiactamponade, bleeding requiring surgery (excluding dental, nasal, skin, hemorrhoid), or bleeding requiring intravenous vasoactive agents Type 3c: Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal), subcategories confirmed by autopsy or imaging or lumbar puncture, or intraocularbleedcompromising vision Mehranet al, Circulation 2011

  14. BleedingAcademicResearchConsortium Type 4 - CABG-relatedbleeding: Perioperative intracranial bleeding within 48 h, reoperation after closure of sternotomy for the purpose of controlling bleeding, transfusion of 5 U whole blood or packed red blood cells within a 48-h period, or chest tube output 2L within a 24-h period Type 5a - Probable fatal bleeding: no autopsy or imaging confirmation but clinicallysuspicious Type 5b - Definite fatal bleeding: overt bleeding or autopsy or imaging confirmation Mehranet al, Circulation 2011

  15. Clinical impact Ndrepepaet al, Circulation 2012

  16. Access site versus non-access site bleeding US CathPCI Registry (2004-2011): 57,246 bleeding events (1.7%) in 3,386,688 PCI procedures Chhatriwallaet al, JAMA 2013

  17. Clarifying the mechanism Peddinghauset al, ClinLabMed 2009

  18. Learninggoals • Scope of the problem • Definitions • Pragmaticapproachtobleeding • Specificrecommendations

  19. Comprehensiveapproachtobleeding Risk-stratificationofpatient/procedure Preventingbleeding Monitoringforbleeding Limitingbleeding Transfusionof RBC Discontinuationofantiplateletagent Reversalofantiplateleteffect Makriset al, Br J Haematol 2012

  20. Bleedingscores www.crusadebleedingscore.com

  21. UK guidelines Makriset al, Br J Haematol 2012

  22. UK guidelines Makriset al, Br J Haematol 2012

  23. UK guidelines Makriset al, Br J Haematol 2012

  24. Usefulnessofthromboelastography-guidedtransfusions Schulman, Hematology 2012

  25. Manyplateletfunctiontests are available Peddinghauset al, ClinLabMed 2009

  26. Butbewareofvariability in assays Santilliet al, J Am CollCardiol 2009

  27. Alsoavoidovertreating: hazardsofanti-fibrinolytics Huttonet al, BMJ 2012

  28. Learninggoals • Scope of the problem • Definitions • Pragmaticapproachtobleeding • Specificrecommendations

  29. Activation and clearance Tanet al, CardiovascTher 2012

  30. Timetonormalplateletfunction Makriset al, Br J Haematol 2012

  31. Aspirin • Oraldrug • Irreversibly inactivates cyclooxygenase • Reversalpossiblewithplatelettransfusion, desmopressin, or rFVIIa Schulman, Hematology 2012; Makriset al, Br J Haematol 2012; Altman et al, J ThrombHaemost 2006

  32. Clopidogrel • Oraldrug • Irreversiblyinactivates the P2Y12 plateletreceptorfor ADP • Reversalpossiblewithplatelettransfusions, desmopressin, methyl prednisolone or rFVIIa Schulman, Hematology 2012; Levineet al, J MedToxicol 2012; Makriset al, Br J Haematol 2012; Leithäuseret al, ClinHemorheolMicrocirc 2008

  33. rFVIIa in healthysubjectsreceiving clopidogrel Skolnicket al, AnesthAnalg 2011

  34. Prasugrel • Oraldrug • Irreversiblyinactivates the P2Y12 plateletreceptorfor ADP • Reversalpossiblewithplatelettransfusions, or desmopressin Zafaret al, J ThrombHaemost 2012

  35. Effectofplatelets on prasugrel Zafaret al, J ThrombHaemost 2012

  36. Ticagrelor • Oraldrug • Reversiblyantagonizes the P2Y12 plateletreceptorfor ADP • Renalclearance • Reversalpossible (onlyanimal/in vitro data) withrFVIIaan FII and platelettransfusion Nylanderet al, J Am CollCardiol 2013

  37. Adjustedindirectcomparison Biondi-Zoccaiet al, Int J Cardiol 2011

  38. WhataboutintravenousglycoproteinIIb/IIIainhibitors? Abciximab: • IV monoclonal antibody • IrreversiblyinactivatesglycoproteinIIb/IIIareceptors • Plasma t1/2 30 minutes, butplateletsremaininhibited 12-24 h • Reversalpossiblewithplatelettransfusions Eptifibatide and tirofiban: • IV drugs • ReversiblyinactivateglycoproteinIIb/IIIareceptors • Plasma t1/2 2.5 hoursforeptifibatide and 1.5 hoursfortirofiban • Renalclearance (thus t1/2longerifrenalfailure) • Reversalmaybeachievedwithdialysis

  39. Pragmaticapproachtoplatelettransfusion Campbell et al, World Neurosurg 2010

  40. PossiblethresholdsforplateletRx Peddinghauset al, ClinLabMed 2009

  41. Take home messages • A comprehensiveapproachtobleedingisrecommended, fromrisk-stratification, toprediction, and management. • Whenbleedingdoesoccur, non-pharmacologicapproachesshouldbeenvisioned first. • Ifthese are failing or unlikelytosucceed, discontinuatonispossible, butitshouldbebased on a multidisciplinaryevaluation. • In highlyselectedcases, reversalwithplatelettranfusions, desmopressin, rFVIIa or otheragents can beimplemented, notwithstanding the major riskofiatrogenicthrombosis.

  42. Manythanksforyourattention Fortheseslides and furtherones on similartopicsfeel free tovisit: www.metcardio.org/slides.html Foradditionaldetails or queriesfeel free tocontact me directly: giuseppe.biondizoccai@uniroma1.it

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