Managing Anti-Coagulation in Endoscopy

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1 Managing Anti-Coagulation in Endoscopy Dushant S. Uppal, MD, MSc Assistant Professor of Medicine Gastroenterology&Hepatology University of Virginia Objectives Understand commonly used antithrombotic agents Understand the risk of GI bleeding in patients on specific antithrombotic agents Understand the thromboembolic event risks when holding antithrombotics Better understand when to hold/resume antithrombotic agents for bleeding or electively. Copyright American College of Gastroenterology 1

2 Anti-thrombotic medications Antiplatelet agents Aspirin Thienopyridines (P2Y12 inhibitors) Anti-coagulant medications Warfarin Direct oral anticoagulants (DOAC) GI Bleeding severity Mild GI bleeding No evidence of ongoing active bleeding or clinically significant bleeding Stable hemodynamics Moderate GI bleeding Clinically significant bleeding or possible ongoing bleeding Stable or easily stabilized hemodynamics Severe GI bleeding Clinically significant bleeding and ongoing GI bleeding Unstable hemodynamics Copyright American College of Gastroenterology 2

3 Anti-Platelet agents Aspirin Irreversible acetylation and inactivation of platelet cyclooxygenase Effect is for duration of the platelet s life (7-10 days) Prolonged bleeding time for 48 hours and up to 8 days Copyright American College of Gastroenterology 3

4 Why not just stop ASA? ASA withdrawal precedes 10% of acute vascular syndromes Time between stopping ASA and acute event: 14.3 days for CVA 8.5 days for acute coronary syndrome 25.8 days for peripheral ischemia Increased bleeding BUT reduced mortality Sung JJ. Ann Intern Med 2010;152:1-9 Copyright American College of Gastroenterology 4

5 So when should we resume ASA after a GI bleed? ACCF/ACG/AHA Consensus document Reintroductions of antiplatelet therapy in high CV-risk patients is reasonable in those who remain free of rebleeding after 3 to 7 days ACG guidelines If given for secondary prevention (ie. Established CV disease) then aspirin should be resumed as soon as possible after bleeding ceases in most patients: ideally within 1-3 days and certainly within 7 days Thienopyridines (P2Y12 inhibitors) Selectively inhibit ADP-induced platelet aggregation Inhibit the binding of ADP to P2 receptors and subsequent activation of the GP IIb/IIIa receptor Inhibition takes several days to develop 40% to 60% inhibition of aggregation after 3 to 5 days Some antiplatelet activity for 7-10 days Copyright American College of Gastroenterology 5

6 Thienopyridine class Dual antiplatelet therapy for ACS - ACC/AHA Intensification of antiplatelet therapy, with the addition of a P2Y12 inhibitor to aspirin monotherapy, as well as prolongation of DAPT, necessitates a fundamental tradeoff between decreasing ischemic risk and increasing bleeding risk. Decisions about treatment with and duration of DAPT require a thoughtful assessment of the benefit/risk ratio, integration of study data, and consideration of patient preference. Levine et al. J Am Coll Cardiol Copyright American College of Gastroenterology 6

7 Dual antiplatelet therapy for ACS - ACC/AHA In general, shorter duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk. A Class I recommendation is made for at least 6-12 months of DAPT Class IIb recommendation is made for prolonged DAPT beyond this initial 6 to 12 month period (optimal duration unknown). ASA should always be continued indefinitely in patients with CAD. The recommended daily dose of aspirin in patient treated with DAPT is 81mg. Levine et al. J Am Coll Cardiol Copyright American College of Gastroenterology 7

8 UGIB post PCI most common site Koskinas KC. Circ Cardiovasc Interv 2015;May;8(5) GI bleeding impact Koskinas KC. Circ Cardiovasc Interv 2015;May;8(5) Copyright American College of Gastroenterology 8

9 Management of thienopyridines with GI bleeding Discontinue if possible Platelet transfusion if reversal needed Switch to clopidogrel if on a newer agent (eg. pasugrel, ticagrelor) clopidogrel has a less efficient conversion to active metabolite and shorter duration Discuss with cardiology: Following control of bleeding Prior to elective endoscopy Copyright American College of Gastroenterology 9

10 Anticoagulants Copyright American College of Gastroenterology 10

11 Warfarin Inhibits production of Factors II, VII, IX and X (vit K dependent) Inhibits proteins C and S Onset between 24 and 96 hours Transient reversal with FFP (4-6 hours) Duration of action of 2 to 5 days Anitcoagulation and therapeutic endoscopy 233 patients post successful therapeutic endoscopy 44% of pts had an INR >1.3 (95% < 2.7) Rebleeding rate 23 % in anticoagulated pts (INR >1.3) 21 % in pts with normal coagulation (INR <1.3) INR not a predictor of rebleeding, length of stay, transfusion requirement, surgery, or mortality Endoscopic therapy is appropriate in mildly to moderately anticoagulated pts Wolf AT. Am J Gastroenterol 2007; 102:290-6 Copyright American College of Gastroenterology 11

12 Warfarin reversal American College of Chest Physicians (2012) 4 factor prothrombin complex concentrate (PCC) contains factors II, VII, IX, and X Vitamin K (5-10 mg slow IV) NO FFP NO individual coagulation factors American Heart Association/American College of Cardiology (2014): valvular heart disease 4 factor PCC or FFP No vitamin K ASGE Rapid Endoscopy with warfarin bleed We suggest that endoscopic therapy not be delayed in patients with serious GI bleeding and an INR < 2.5 * INR at time of endoscopy NOT predictive of rebleeding Acosta RD, Abraham NS, ASGE SOP. Gastrointest Endosc 2016; 83: 3-16 Copyright American College of Gastroenterology 12

13 Management of warfarin with GI bleeding Continue warfarin if mild bleeding Reduce target INR to Monitor INR levels closely Consider a switch to a DOAC Consider if difficulty controlling INR level Switch to a DOAC with a lower bleed risk If bleeding occurred on both warfarin and ASA Stop warfarin if possible and use low-dose ASA Resuming warfarin after GI bleeding ASGE: Restart warfarin following GI bleed within 4-7 days Same day restart with low risk endoscopic stigmata Witt DM. Arch Intern Med 2012; 172(19): Acosta RD, Abraham NS, ASGE SOP. Gastrointest Endosc 2016; 83: 3-16 Copyright American College of Gastroenterology 13

14 Bleeding post polypectomy in polyps <1cm in anticoagulated (warfarin) pts Horiuchi A. Gastrointest Endosc 2014; 79(3): >1cm Non-thermal polypectomy < 1cm Copyright American College of Gastroenterology 14

15 Direct oral anticoagulants (DOAC) Factor Xa or IIa (thrombin) inhibitors At least as effective as warfarin in preventing CVAs in AF Convenient - Oral fixed dose without coagulation management Normal coagulation within hours after DOAC dose is held Copyright American College of Gastroenterology 15

16 Desai J. Gastrointest Endosc 2013;7(2): Desai J. Gastrointest Endosc 2013;7(2): Copyright American College of Gastroenterology 16

17 Management of DOAC during active bleed If ingestion < 2 hours prior -> consider oral charcoal Maximize renal excretion Dabigatran 80% Rivaroxaban 50% Apixaban 40% Hemodialysis for severe GI bleeding Consider PCC for severe bleeding No specific antidotes until recently. Idarucizumab Human monoclonal Ab with high affinity for dabigatran Cost ~ $3500/dose Andexanet alfa Reversal agent against direct and indirect Factor Xa inhibitors PER977 Synthetic water soluble molecule directly binds to heparin, LMWH and DOACs Copyright American College of Gastroenterology 17

18 Tips for management of DOACs in GI bleeding Can measure the anticoagulation effect Dabigatran greater effect on PTT Xa inhibitors greater effect on PT Switch to an alternative DOAC if cannot stop Apixaban has a lower risk of GI bleeding Be aware of possible reversal agents Dabigatran can be reversed Factor Xa inhibitor inhibitors soon available Pragmatic paradigm for DOACs with GI bleed Mild GI bleeding No change to medications No reason to reverse Moderate GI bleeding Hold antithrombotic meds if possible Reverse if ongoing bleeding Restart after endoscopy in 1-7 days (generally should not be held for longer) Severe GI bleeding Hold antithrombotic medications Reverse Restart when clinically stable and monitor (within 7 days) Copyright American College of Gastroenterology 18

19 Resume anticoagulation if needed! Patel et al. JACC Vol. 61, No. 6, 2013: Elective anticoagulation management (ASGE) nes: Acosta RD, Abraham NS, ASGE SOP. Gastrointest Endosc 2016; 83: 3-16 Copyright American College of Gastroenterology 19

20 Elective anticoagulation management Acosta RD, Abraham NS, ASGE SOP. Gastrointest Endosc 2016; 83: 3-16 Summary ASA Resume ASAP once bleeding controlled Continue 81mg for elective procedures Thienopyridines Discontinue for active bleeding Discuss necessity with Cardiology once bleeding controlled (consider switch to clopidogrel) Hold for 5 days prior to elective procedures Copyright American College of Gastroenterology 20

21 Summary Warfarin Reverse with PCC +/- vitamin K for mod severe bleeding Consider switch to DOAC once bleeding controlled Hold for 7 days +/- bridge depending on risk prior to elective procedures DOAC Discontinue for active bleeding Consider "reversal agent" for dabigatran Hold for prescribed period of time prior to elective procedures Resources ASGE: uidelines/antithrombotics.pdf ACCP: 9/11026.pdf Copyright American College of Gastroenterology 21

22 Thank You Copyright American College of Gastroenterology 22

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