Anticoagulation

Overview

2018

Jed Delmore, MD, FACS, FACOG

Professor Obstetrics and Gynecology

University of Kansas School of Medicine, Wichita

The ideal lecture is like a

miniskirt.

Short enough to get your

attention, and long enough to

cover the important parts.

Modified and stolen from a TED Talk.

Unfortunately, this talk is an

evening gown.

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

Anticoagulation

Prophylactic vs. Therapeutic

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

Antiplatelet Therapy

Coagulation

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

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

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

Discontinuing AnticoagulationAssessing Peri-operative Risk

▪ Non-valvular atrial fibrillation

▪ Assessing risk of stroke associated with discontinuing

anticoagulation

▪ CHADS2

▪ CHADS2DS2-VASc

Non-valvular atrial fibrillationAssessing risk of stroke associated with discontinuing anticoagulation

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.

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

Common

Anticoagulation

Drugs

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

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

Bridging Anticoagulation

J Am Coll Cardiol 2015;66:1392-403

J AM Coll Cardiol 2015;66:1392-403

J AM Coll Cardiol 2015;66:1392-403

Timing of discontinuation of

anticoagulation for elective surgery

Trauma Surg Acute Care Open 2016;1:1-7.

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.

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

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

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

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

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

We have reached the

hem of the dress!

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.