anticoagulation overview 2018 - wesley ob/gyn · 9/5/2018 · anticoagulation overview 2018 jed...
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Anticoagulation
Overview
2018
Jed Delmore, MD, FACS, FACOG
Professor Obstetrics and Gynecology
University of Kansas School of Medicine, Wichita
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The ideal lecture is like a
miniskirt.
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Short enough to get your
attention, and long enough to
cover the important parts.
Modified and stolen from a TED Talk.
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Unfortunately, this talk is an
evening gown.
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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
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Anticoagulation
Prophylactic vs. Therapeutic
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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
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Antiplatelet Therapy
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Coagulation
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Indication Duration
Antiphospholipid Syndrome Indefinite
DVT & PE
Transient/reversible risk factors 3 months
Unprovoked At least 3 months, then re-evaluate
Second episode of unprovoked Extended
Non-valvular Atrial
Fibrillation/Flutter
CHADS2 = 0 (low CVA risk) No therapy
CHADS2 = 1 (intermediate CVA risk) DOAC (direct-acting oral anticoagulant)
CHADS2 = ≥2 (high CVA risk) DOAC (direct-acting oral anticoagulant)
With mitral stenosis Long-term
With stable CAD Long-term
Prior to/following cardioversion to NSR 3-4 weeks
Mechanical Heart Valve
Aortic Long-term
Mitral Long-term
Bioprosthetic Heart Valve
Aortic ASA
Mitral 3 month anticoagulation then ASA
Cardioembolic Ischemic Stroke DOAC (direct-acting oral anticoagulant)
Anticoagulation
Indications
Adapted from 9th
edition of Chest
Guidelines
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Preprocedural Continuation or Discontinuation of
Anticoagulation
Continue or Discontinue
Anticoagulation
Risk of Adverse Event
Off TherapyRisk of Adverse Event
On Therapy
Risk of Bleeding
Associated with ProcedureRisk of Adverse Event or
Bleeding while Bridging
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Discontinuing AnticoagulationAssessing 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
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Discontinuing AnticoagulationAssessing Peri-operative Risk
▪ Non-valvular atrial fibrillation
▪ Assessing risk of stroke associated with discontinuing
anticoagulation
▪ CHADS2
▪ CHADS2DS2-VASc
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Non-valvular atrial fibrillationAssessing risk of stroke associated with discontinuing anticoagulation
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Venous ThromboembolismAssessing 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.
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Prosthetic Heart ValvesAssessing 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
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Common
Anticoagulation
Drugs
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Drug Mechanism of
Action
Half-Life Time to Peak
Warfarin Inhibits Vit. K
dependent Factors
II, VII, IX & X
40 hours 4-5 days
Unfractionated
Heparin
Inhibits Factors Xa
& IIa via activation
of AT3, Inhibit
thrombin activation
1.5 hours sub-q
30 min. IV
4 hours
2 hours
Enoxaparin
Daltaparin
(LMWH)
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 Direct
Thrombin(IIa)
Inhibitor
12-14 hours 1 hour
Bivalirudin
(infusion)
Direct
Thrombin(IIa)
Inhibitor
25 minutes 4 hours
Argatroban
(infusion)
Direct
Thrombin(IIa)
Inhibitor
45 minutes 1-3 hours
Peak Effect
&
Half-life
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Drug Mechanism of
Action
Monitoring Renal Dosing Potential
Reversal Agents
Warfarin Inhibits Vit. K
dependent Factors
II, VII, IX & X
PT/INR No Vit. K, Fresh Frozen
Plasma (FFP),
Prothrombin
Complex
Concentrates(
PCC), rVIIa
Unfractionated
Heparin
Inhibits Factors Xa
& IIa via activation
of AT3, Inhibit
thrombin activation
aPTT No Protamine sulfate
Enoxaparin
Daltaparin
(LMWH)
Same as UFH Anti-factor Xa
(not routine)
Yes Protamine sulfate
Fondaparinux Factor Xa inhibitor Anti-factor Xa Yes Possibly four-
complex PCC
Rivaroxiban Factor Xa inhibitor Anti-factor Xa Yes Possibly four-
complex PCC
Apixaban Factor Xa inhibitor Anti-factor Xa Unknown Possibly four-
complex PCC
Dabigatran Direct Thrombin(IIa)
Inhibitor
Thrombin Time,
Ecarin clotting time
Yes Possibly four-
complex PCC
Bivalirudin Direct Thrombin(IIa)
Inhibitor
Thrombin Time,
Ecarin clotting time
Yes Possibly four-
complex PCC
Argatroban Direct Thrombin(IIa)
Inhibitor
Thrombin Time,
Ecarin clotting time
No Possibly four-
complex PCC
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Bridging Anticoagulation
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J Am Coll Cardiol 2015;66:1392-403
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J AM Coll Cardiol 2015;66:1392-403
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J AM Coll Cardiol 2015;66:1392-403
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Timing of discontinuation of
anticoagulation for elective surgery
Trauma Surg Acute Care Open 2016;1:1-7.
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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.
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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
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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
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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
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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
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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 1995.
▪ 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
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We have reached the
hem of the dress!
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References
▪ Kovac RJ et al. Practical management of anticoagulation in patients with atrial fibrillation. J Am Coll Cardiol 2015:;66:1340-60
▪ The perioperative management of antithrombotic therapy: American College of Chest
Physicians Evidence-based Clinical Practice Guidelines (8th 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.