Managing Anticoagulants, Antiplatelets, and NSAIDS in the Interventional Radiology Setting. Amy Huggins, BSN, RN
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1 Managing Anticoagulants, Antiplatelets, and NSAIDS in the Interventional Radiology Setting Amy Huggins, BSN, RN
2 Objectives Recognize bleeding risk based on classes of IR procedures Differentiate between anticoagulants, antiplatelet agents and NSAIDS and how they work Discuss monitoring parameters to evaluate the effects of blood thinners Determine how long to hold medications prior to procedure Understand reversal agents and when each would be most appropriate
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4 Procedure Categories I II III Low Bleeding Risk/Easily Detectable or Controlled Moderate Bleeding Risk Significant Bleeding Risk/Bleeding Difficult to Detect of Control J Vasc Interv Radiol. 2013; 24:641-5.
5 Procedure Examples I II III Nontunneled Venous Catheter Placement/Removal Angiograms (with access up to 7 FR) TIPS Dialysis Access Interventions Venous Interventions Renal Biopsy IVC Filters Catheter Exchanges Tunneled Catheters Nephrostomy Tube Placements Paras & Thoras Spinal Procedures Biliary Interventions J Vasc Interv Radiol. 2013; 24:641-5.
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8 Antiplatelets Blood Thinners Anticoagulants NSAIDS
9 Antiplatelet Agents
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12 1
13 Antiplatelets Aspirin P2Y12 Inhibitors GP IIb/IIIa Inhibitors Ticlodipine (Ticlid) Eptifibatide (Integrilin) Clopidogrel (Plavix) Abciximab (Reopro) Prasugrel (Effient)) Tirofiban (Aggrastat) Ticagrelor (Brilinta)
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15 Aspirin Acetylates cyclooxygenase-1 and -2 (COX) enzymes Irreversibly binds, inhibits platelet aggregation Half-Life Hold for Class I Hold for Class II Hold for Class III 3-6 Hours Do not withhold Do not withhold 5 days J Vasc Interv Radiol. 2013; 24:641-5.
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17 P2Y12 Inhibitors Ticlopidine (Ticlid) Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brilinta)
18 P2Y12 Inhibition
19 P2Y12 Inhibitors* Medication Clopidogrel (Plavix) Ticlopidine (Ticlid) Prasugrel (Effient) Ticagrelor (Brilinta) Half-Life Hold for Class I Hold for Class II Hold for Class III 6 hours 0-5 days 5 days 5 days 12.5 hours 0-5 days 7 days 7 days 2-15 hours, avg appx days 5 days 5 days 7 hours 0-5 days 5 days 5 days J Vasc Interv Radiol. 2013; 24: Dtsch Arztebl Int. 2013;110(31-32):525-32
20 GP IIb/IIIa Inhibitors Eptifibatide (Integrilin) Abciximab (Reopro) Tirofiban (Aggrastat)
21 GP IIb/IIIa Inhibition
22 GP IIb/IIIa Inhibitors Medication Half-Life Hold for Class I Hold for Class II Hold for Class III Abciximab (Reopro) 30 minutes hours aptt 50 s ACT 150 s 24 hours aptt 50 s ACT 150 s 24 hours aptt 50 s ACT 150 s Eptifibatide (Integrilin) 2.5 hours Immediately prior to procedure 4 hours 4 hours Tirofiban (Aggrastat) 2 hours Immediately Prior to Procedure 4 hours 4 hours J Vasc Interv Radiol. 2013; 24:641-5.
23 Cilostazol (Pletal) Inhibits thrombosis and platelet aggregation Less potent platelet inhibitor than Plavix Half Life: hours Not listed in SIR CPG J Vasc Interv Radiol. 2013; 24:641-5.
24 Reinitiation of Antiplatelets When postoperative bleeding risk has subsided Aspirin takes effect almost immediately after it is taken P2Y12 Inhibitors can have a delayed impact Could consider a loading dose Plavix mg Prasugrel 60 mg Blood Dec 6; 120(24):
25 Anticoagulant Agents
26 Anticoagulants Vitamin K Antagonist Factor Xa Inhibitors Direct Thrombin Inhibitors Unfractionated Heparin Low Molecular Weight Heparin Warfarin (Coumadin) Rivaroxaban (Xarelto) Dabigatran (Pradaxa) Enoxaparin (Lovenox) Apixaban (Eliquis) Bivalirudin (Angiomax) Daltaparin (Fragmin) Fondaparinux (Artixtra) Argatroban
27 Warfarin Vitamin K Antagonist Inhibits Vitamin K Clotting Factors II, IX, X, and VII Delayed onset based on half life of the affected factors Drug Interactions affect INR Half-Life Hold for Class I hours 3-5 days INR 2.0 Hold for Class II 5 days INR 1.5 Hold for Class III 5 days INR 1.5 J Vasc Interv Radiol. 2013; 24:641-5.
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29 Factor Xa Inhibitors Fonadparinux (Arixtra) Apixaban (Eliquis) Rivaroxaban (Xaralto)
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31 Factor Xa Inbibitors Medication Fonadparinux (Arixtra) Apixaban (Eliquis) Rivaroxaban (Xaralto) Half-Life Renal Elimination hours 77% Hold for Class I Do not withhold Hold for Class II 2-3 days (CrCl >50 ml) 3-5 days (CrCl <50 ml) Hold for Class III 2-3 days (CrCl >50 ml) 3-5 days (CrCl <50 ml) 8-15 hours 27% 1-2 days 2-4 days 2-4 days 5-9 hours, hours in the elderly 66% 1-2 days 2-4 days 2-4 days Am J Health-Syst Pharm May;70:S3-11 J Vasc Interv Radiol. 2013; 24:641-5.
32 Rivaroxaban and Apixaban Hold times mildly dependent on renal function Creatinine Clearance Last Dose before Minor Procedure > 50 ml/min ml/min ml/min 2 4 Last Dose before Major Procedure Am J Health-Syst Pharm May;70:S3-11 Am J Health-Syst Pharm Sept;69:
33 Direct Thrombin Inhibitors Dabigatran (Pradaxa) Bivalirudin (Angiomax) Argatroban
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35 Direct Thrombin Inhibitors Medication Half-Life Hold for Class I Hold for Class II Hold for Class III Argatroban minutes Do not withhold Hold 4 hours, defer procedure if possible Hold 4 hours, defer procedure if possible Bivalirudin (Angiomax) minutes Do not withhold 2-3 hours (CrCl >50 ml/min) 3-5 hours (CrCl <50 ml/min) 2-3 hours (CrCl >50 ml/min) 3-5 hours (CrCl <50 ml/min) Dabigatran (Pradaxa) hours Do not withhold 2-3 days (CrCl >50 ml/min) 3-5 days (CrCl <50 ml/min) 2-3 days (CrCl >50 ml/min) 3-5 days (CrCl <50 ml/min) Am J Health-Syst Pharm May;70:S3-11 Am J Health-Syst Pharm Sept;69:
36 Unfractionated Heparin Combines with antithrombin III (Heparin cofactor) Prevents the conversion of prothrombin to thrombin Inactivates the activated Factor X Half-Life Hold for Class I Hold for Class II Hold for Class III minutes No consensus, check aptt No consensus, check aptt Withhold 2-4 hours before procedure, aptt 1.5 x control J Vasc Interv Radiol. 2013; 24:641-5.
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38 Low Molecular Weight Heparins Enoxaparin (Lovenox) Dalteparin (Fragmin)
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40 Low Molecular Weight Heparins Medication Half-Life Hold for Class I Hold for Class II Hold for Class III Enoxaparin (Lovenox) hours 1 dose or 12 hours 1 dose or 12 hours 2 doses or 24 hours Dalteparin (Fragmin) 2-7 hours 1 dose or 12 hours 1 dose or 12 hours 2 doses or 24 hours J Vasc Interv Radiol. 2013;24:641-5
41 Could use as Bridge Therapy For patients with high risk when off anticoagulation Stop Coumadin 3-5 days prior and use Lovenox up until hours before procedure Restart the Coumadin post and continue Lovenox until goal INR is reached Blood Dec 6; 120(24):
42 Restarting Anticoags When post procedure risk has subsided
43 NSAIDS
44 NSAIDS Short Acting Intermediate Acting Long Acting Ibuprofen Naproxen Meloxicam Diclofenac Sulindac Nabumetone Ketoprofen Diflunisal Piroxicam Indomethacin Celecoxib J Vasc Interv Radiol. 2013;24:641-5
45 NSAIDS Like ASA, NSAIDs block the COX Receptors Unlike ASA, NSAIDS diminish over time as they circulate Medication Half-Life Hold for Class I Hold for Class II Hold for Class III Short Acting 2-6 hours Do not withhold Do not withhold 24 hours Intermediate Acting 7-15 hours Do not withhold Do not withhold 2-3 days Long Acting > 20 hours Do not withhold Do not withhold 10 days J Vasc Interv Radiol. 2013;24:641-5
46 Monitoring for Efficacy
47 Lab Values Lab Value PT INR Dilute PT (dpt) aptt Thrombin Time (TT) Ecarin Clotting Time (ECT) Chromogenic Assays Heptest Prothrombinase--induced clotting time (PiCT) Description Time in seconds for plasma to coagulate after addition of thromboplastin Calculation of PT that accounts for manufacturer s sensitivity index Similar to PT, dilution increases the sensitivity Reflects activity of Factors II, V, VIII-XII Activity of thrombin in plasma Measures thrombin generation Color changes of substrate specific for a certain factor Measures the inhibition of exogenous Factor Xa Involves phospholipids, Fxa, & enzymes to activate factor V to measures time & effect of anticoagulant
48 Lab Values Rivaroxaban (Xaralto) Lab Value Utility Comments PT Widely available, more sensitive at higher concentrations Dilute PT (dpt) Reagent variability, not widely available aptt Less sensitive than PT, not ideal Thrombin Time (TT) No effect Ecarin Clotting Time (ECT) Unlikely to have an effect Chromogenic Anti Factor IIa Assays Heptest Prothrombinase--induced clotting time (PiCT) Accurate & Precise, most promising Sensitive at low and high concentrations. Not widely available Not widely available, not FDA approved Am J Health-Syst Pharm Sept; 69: Am J Health-Syst Pharm May; 70:S21-31 Blood Dec 6; 120(24):
49 Lab Values Apixaban (Eliquis) Lab Value Utility Comments PT Dilute PT (dpt) Widely available, more sensitive at higher concentrations More sensitive than PT, not widely available or FDA approved aptt Less sensitive than PT, not ideal Thrombin Time (TT) No effect Ecarin Clotting Time (ECT) Unlikely to have an effect Chromogenic Anti Factor IIa Assays Heptest Accurate & Precise, most promising Sensitive at low and high concentrations. Not widely available Prothrombinase--induced Clotting time (PiCT) Not widely available, not FDA approved Am J Health-Syst Pharm Sept; 69: Am J Health-Syst Pharm May; 70:S21-31 Blood Dec 6; 120(24):
50 Lab Values Dabigatran (Pradaxa) Lab Value Utility Comments PT Not ideal, but widely available Dilute PT (dpt) aptt Thrombin Time (TT) Ecarin Clotting Time (ECT) Chromogenic Anti Factor IIa Assays More sensitive than PT, not widely available Availability & sensitivity support use Limited utility in quantifying extent of anticoagulation Sensitive at all concentrations, limited availability Minimal data, not available Heptest Poor correlation, not useful PiCT Not studied, not likely to be useful Am J Health-Syst Pharm Sept; 69: Am J Health-Syst Pharm May; 70:S21-31 Blood Dec 6; 120(24):
51 Strategies for Reversals
52 Blood Products Packed Red Blood Cells Maintain oxygenation and hemoglobin Will increase Hgb by appx 1 Fresh Frozen Plasma Contains clotting factors contained in human plasma 20-30% increase in plasma clotting factors Platelets Human platelet concentrates May give in combo with DDAVP
53 Prothrombin Complex Concentrate (PCC) Profilnine 3 factors II, IX, X May use multiple doses No max dose Kcentra 4 factors II, VII, IX, X Repeat dosing not recommended Max dosing weight = 100kg Dosing is the same for both: INR <4: 25 units/kg INR 4-6: 35 units/kg INR > 6: 50 units/kg Am J Health-Syst Pharm May;70:S3-11
54 FFP vs. PCC Dose Adverse Reactions FFP Commonly appx 2 unites ml/kg (appx ml/unit) Hemolytic Reaction Acute Lung Injury Hypersensitivity PCC Expressed as Factor IX units/kg Hypersensitivity Thrombosis (1-2%) Price $40/pack $1.27 per unit Advantages Disadvantages Contains all factors found in human plasma Large Volume Need to be thawed Risk for transmission of disease Fast administration No type and cross needed Expensive Risk of infectious disease transmission
55 Factor VIIa NovoSeven RT Recombinant Activated Factor VII Dose mcg/kg, max 100 mcg/kg Higher risk for thrombosis with higher dosing Dosing regimen evidence isn t clear Activated products carry a higher risk of arterial thrombosis
56 Vitamin K Can be used to reverse Warfarin Can be used if patient cannot wait for Warfarin to wear off or if they are actively bleeding Route Reversal Time Dose IV hours 5-10 mg PO 24 hours 2-5 mg
57 Protamine Sulfate Used to reverse heparin (unfractionated and low molecular weight) Max dose of 50 mg As time passes from heparin administration, dose needed drops 1 mg Protamine Neutralizes Unfractionated Heparin Low Molecular Weight Heparin Dalteparin (Fragmin) 100 units 1 mg 100 anti-xa units
58 Desmopressin (DDAVP) De-amino d-arginin vasopressin Often given in addition to platelets Increases Von Willebrand Factor and Factor XIII Dosing 0.3 mcg/kg in 100 ml of saline administered over 30 minutes Effect is immediate J Thromb Haemost 2011;9: J Thromb Haemost 2003;1:682-9
59 Reversal of Selected Agents Drug Class Antidote Dialysis Recommendations Antiplatelets Vitamin K Antagonists Warfarin (Coumadin) Dabigatran (Pradaxa) Desmopressin (DDAVP) Vitamin K In Development Acute ASA toxicity only No Yes Platelets - ASA only 1 pack - Combo Therapy 2 packs Factor VIIa prbc Vitamin K +/- PCC FFP prbcs PCC 50 units/kg IV Factor VIIa 90 mcg/kg IV FFP prbc
60 Reversal of Selected Agents Drug Class Antidote Dialysis Recommendations Factor Xa Inhibitors Heparin & Low Molecular Weight Heparins In Development Protamine Sulfate No No PCC 50 units/kg IV Factor VIIa 30 mcg/kg IV FFP prbc FFP prbc
61 Possible New Agents on the Horizon Potential Future Reversals Dabigatran monoclonal antibody fragment Rivaroxaban, apixaban, LMWH antidote Factor X Fragment New Agents being Studied Cangrelor P2Y12 Inhibitor, IV Route with Rapid Onset Endoxaban Factor Xa Inhibitor, PO Route Blood Dec 6; 120(24): Best Pract Res Clin Haematol Jun;26(2):
62 Questions How urgent is the procedure? Can it wait for the agent to wear off on its own? What reversal strategy is most appropriate for the agent in use? Will the patient need to restart the medication? If so, what would be the safest way to do so?
63 Thank you to Carlion Clinic Pharmacy Joleen Bierlein, Pharm.D.
64 References 1) Patel IJ, Davidson JC, Nikolic B, et al. Addendum of newer anticoagulants to the SIR consensus guideline. J Vasc Interv Radiol. 2013; 24: ) Schlitt A, Jambor C, Spannagl M, et al. The perioperative management of treatment with anticoagulants and platelet aggregation inhibitors. Dtsch Arztebl Int. 2013;110(31-32): ) Ortel TL. Perioperative management of patients on chronic antithrombotic therapy. Blood Dec 6; 120(24): ) Nutescu EA. Oral anticoagulant therapies: Balancing the risks. Am J Health-Syst Pharm May; 70:(S3-11) 5) Miyares MA, Davis K. Newer oral anticoagulants: A review of laboratory monitoring options and reversal agents in the hemorrhagic patient. Am J Health-Syst Pharm Sept; 69: ) Dager WE. Developing a management plan for oral anticoagulant reversal. Am J Health-Syst Pharm May; 70:(S21-S31) 7) Levi M, Eerenberg E, Kamphuisen PW. Bleeding risk and reversal strategies for old an new anticoagulants and antiplatelet agents. J Thromb Haemost 2011; 9: ) Kalus JS. Pharmacologic interventions for reversing the effects of oral anticoagulants. Am J Health-Syst Pharm May; 70:(S12-S21). 9) Kaufmann JE, Vischer UM. Cellular mechanisms of the hemostatic effects of desmopression (DDAVP). J Thromb Haemost 2003;1: ) Majeed A, Schulman S. Bleeding and antidotes in new oral anticoagulants. Best Pract Res Clin Haematol Jun;26(2):
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