Anticoagulation Overview Jed Delmore, MD, FACS, FACOG Professor Obstetrics and Gynecology University of Kansas School of Medicine, Wichita

Transcription

1 Anticoagulation Overview 2018 Jed Delmore, MD, FACS, FACOG Professor Obstetrics and Gynecology University of Kansas School of Medicine, Wichita

2 The ideal lecture is like a miniskirt.

3 Short enough to get your attention, and long enough to cover the important parts. Modified and stolen from a TED Talk.

4 Unfortunately, this talk is an evening gown.

5 Anticoagulation Overview Objectives Therapeutic vs. Prophylactic Anticoagulation vs. Antiplatelet Therapy Indications for anticoagulation therapy Options for therapeutic anticoagulation Drug overview Pharmacology Assessing risk of bleeding vs. stopping therapy Peri-operative management of anticoagulation Stopping Bridging Resuming

6 Anticoagulation Prophylactic vs. Therapeutic

7 Antiplatelet Therapy Platelet lifespan 7-9 days Antiplatelet therapy is irreversible Antiplatelet therapy Inhibition of platelet aggregation by inhibition of Cyclooxygenase 1 (ASA) Inhibition of platelet activation by inhibition of P2Y12 receptor for ADP ( ie. Clopidogrel) Off therapy for 5-10 days prior to surgery, based on the original indication for therapy and risk of surgical bleeding

8 Antiplatelet Therapy

9 Coagulation

10 Anticoagulation Indications Indication Antiphospholipid Syndrome DVT & PE Transient/reversible risk factors Unprovoked Second episode of unprovoked Non-valvular Atrial Fibrillation/Flutter CHADS 2 = 0 (low CVA risk) CHADS 2 = 1 (intermediate CVA risk) CHADS 2 = 2 (high CVA risk) With mitral stenosis With stable CAD Prior to/following cardioversion to NSR Mechanical Heart Valve Duration Indefinite 3 months At least 3 months, then re-evaluate Extended No therapy DOAC (direct-acting oral anticoagulant) DOAC (direct-acting oral anticoagulant) Long-term Long-term 3-4 weeks Adapted from 9 th edition of Chest Guidelines Aortic Mitral Bioprosthetic Heart Valve Aortic Mitral Cardioembolic Ischemic Stroke Long-term Long-term ASA 3 month anticoagulation then ASA DOAC (direct-acting oral anticoagulant)

11 Preprocedural Continuation or Discontinuation of Anticoagulation Risk of Adverse Event Off Therapy Risk of Adverse Event On Therapy Continue or Discontinue Anticoagulation Risk of Bleeding Associated with Procedure Risk of Adverse Event or Bleeding while Bridging

12 Discontinuing Anticoagulation Assessing Peri-operative Risk Non-valvular atrial fibrillation Assessing risk of stroke associated with discontinuing anticoagulation Venous thromboembolic disease Assessing risk of recurrent VTE with discontinuation of anticoagulation Mechanical heart Valves Assessing risk of embolic event associated with discontinuation of anticoagulation

13 Discontinuing Anticoagulation Assessing Peri-operative Risk Non-valvular atrial fibrillation Assessing risk of stroke associated with discontinuing anticoagulation CHADS 2 CHADS 2 DS 2 -VAS c

14 Non-valvular atrial fibrillation Assessing risk of stroke associated with discontinuing anticoagulation

15 Venous Thromboembolism Assessing peri-operative risk of recurrent VTE associated with discontinuation of anticoagulation Low Risk: (<5% annual risk VTE) History of VTE > 12 months ago Intermediate Risk: 5-10% annual risk of VTE) VTE within 3-12 months Non-severe thrombophilia (Factor V Leiden or prothrombin gene mutation) Active cancer current therapy or within 6 months High Risk: (>10% annual risk of VTE) VTE within 3 months Severe thrombophilia ( Protein S/C/antithrombin deficiency or antiphospholipid antibodies.

16 Prosthetic Heart Valves Assessing peri-operative risk of embolic event associated with discontinuation of anticoagulation Intermediate Risk: Aortic bileaflet or current-generation single tilting valves with no risk factors for thromboembolism Bioprosthetic valves and atrial fibrillation, atrial thrombus or enlargement, prior stroke, or TIA > 6 months, HTN, diabetes, CHF, or age > 75 years. High Risk: Aortic caged-ball valve or older generation valves Any mechanical valve with atrial fibrillation, atrial thrombus, or enlargement, stroke, TIA, CHF, or hypercoagulable state Any mechanical mitral valves

17 Common Anticoagulation Drugs

18 Peak Effect & Half-life Drug Warfarin Unfractionated Heparin Enoxaparin Daltaparin (LMWH) Mechanism of Action Inhibits Vit. K dependent Factors II, VII, IX & X Inhibits Factors Xa & IIa via activation of AT3, Inhibit thrombin activation Half-Life Time to Peak 40 hours 4-5 days 1.5 hours sub-q 30 min. IV 4 hours 2 hours Same as UFH 3-4 hours 2-4 hours Fondaparinux Factor Xa inhibitor 17 hours 3-4 days Rivaroxiban Factor Xa inhibitor 9-13 hours 2-4 hours Apixaban Factor Xa inhibitor 8-15 hours 3 hours Dabigatran Bivalirudin (infusion) Direct Thrombin(IIa) Inhibitor Direct Thrombin(IIa) Inhibitor hours 1 hour 25 minutes 4 hours Argatroban (infusion) Direct Thrombin(IIa) Inhibitor 45 minutes 1-3 hours

19 Drug Warfarin Unfractionated Heparin Enoxaparin Daltaparin (LMWH) Mechanism of Action Inhibits Vit. K dependent Factors II, VII, IX & X Inhibits Factors Xa & IIa via activation of AT3, Inhibit thrombin activation Same as UFH Monitoring Renal Dosing Potential Reversal Agents PT/INR No Vit. K, Fresh Frozen Plasma (FFP), Prothrombin Complex Concentrates( PCC), rviia aptt No Protamine sulfate Anti-factor Xa (not routine) Yes Protamine sulfate Fondaparinux Factor Xa inhibitor Anti-factor Xa Yes Possibly fourcomplex PCC Rivaroxiban Factor Xa inhibitor Anti-factor Xa Yes Possibly fourcomplex PCC Apixaban Factor Xa inhibitor Anti-factor Xa Unknown Possibly fourcomplex PCC Dabigatran Direct Thrombin(IIa) Inhibitor Thrombin Time, Ecarin clotting time Yes Possibly fourcomplex PCC Bivalirudin Direct Thrombin(IIa) Inhibitor Thrombin Time, Ecarin clotting time Yes Possibly fourcomplex PCC Argatroban Direct Thrombin(IIa) Inhibitor Thrombin Time, Ecarin clotting time No Possibly fourcomplex PCC

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21 Bridging Anticoagulation

22 J Am Coll Cardiol 2015;66:

23 J AM Coll Cardiol 2015;66:

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25 J AM Coll Cardiol 2015;66:

26 Timing of discontinuation of anticoagulation for elective surgery Trauma Surg Acute Care Open 2016;1:1-7.

27 Pre-procedural Assessment of Anticoagulated Patient Indication for the anticoagulation? Risk of surgical bleeding? Risk of adverse event if anticoagulation is stopped or continued? Is anticoagulation bridge needed? Communicate with the care provider managing the anticoagulation.

28 Case # 1 52 year old with enlarging uterus scheduled for TAH, BSO History of rate controlled atrial fibrillation, HTN, Type II DM Medications: Warfarin 5 mg PO daily Amiodarone 600 mg PO daily Hydrochlorothiazide 12.5 mg PO daily Metformin 500 mg PO BID

29 Case # 2 58 year old with menopausal bleeding, endometrial stripe 11 mm. Scheduled for hysteroscopy, D&C History of controlled atrial fibrillation, HTN, Type II DM Medications: Warfarin 5 mg PO daily Amiodarone 600 mg PO daily Hydrochlorothiazide 12.5 mg PO daily Metformin 500 mg PO BID

30 Case # 3 42 year old with endometriosis, Scheduled for robotic hysterectomy, BSO, resection of endometriosis. History of RLE DVT 5 months ago following knee surgery Medications: Rivaroxaban (Xarelto) 20 mg PO daily Multivitamins

31 Case # 4 64 year old with 8 cm solid adnexal mass. Scheduled for hysterectomy, BSO, possible staging. History of recurrent RLE DVT, and pulmonary embolism 7 months ago. Medications: Rivaroxaban (Xarelto) 20 mg PO daily Venlafaxine 75 mg po daily

32 Case # 5 64 year old with serous endometrial carcinoma. Scheduled for robotic hysterectomy, BSO, sentinel node sampling. History of mechanical mitral and aortic valve replacement in Medications: Warfarin 5 mg PO five days weekly, and 7.5 md PO two days weekly. Atorvastatin 20 mg PO daily HCTZ 12.5 mg PO daily

33 We have reached the hem of the dress!

34 References Kovac RJ et al. Practical management of anticoagulation in patients with atrial fibrillation. J Am Coll Cardiol 2015:;66: The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8 th Edition) Chest 2008 Jun;133(6 Suppl):299s-339s. McBeth PB, et al. A surgeon s guide to anticoagulant and antiplatelet medications part one: Warfarin and new direct oral anticoagulant medications. Trauma Surg Acute Care Open 2016;1:1-5. Yeung LYY et al. Surgeon s guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation. Trauma Surg Acute Care Open 2016;1:1-7 Harter K, et al. Anticoagulation Drug Therapy: A Review. West J Emerg med. 2015;16(1):11-17.