Declotting inpatient

anticoagulationCaitlyn Haines, PGY-2

TJUH Family Medicine Resident Lecture Series

Learning Objectives● Understand the hemostatic process including a review of the coagulation

cascade and role of platelets in forming the platelet plug.● Recognize mechanism of action of a variety of anticoagulant agents as

well as indications for use and dosing.● Improve knowledge of perioperative anticoagulation.● Review indications & mechanisms of reversal.● Explore indications for VTE prophylaxis in the era of COVID.

What we won’t cover● Cessation of anticoagulation in older adults.● Perioperative management of medications other than anticoagulants.● Outpatient monitoring/transitioning between anticoagulants.

Disclosures● None

Introduction to anticoagulation

Why anticoagulate?● Hypercoagulable state● Active clot ● Cardiac pathology● Valve replacement/stenting

Platelet function in clot formation● Hemostasis is achieved through three steps:

○ Vascular spasm/vasoconstriction○ Platelet plug formation○ Coagulation

● Platelet plug formation: activation, aggregation & adherence

The Coagulation Cascade

Targets of anticoagulation: ● Thrombin (Factor IIa)● Protein C & S● Factor Xa ● Vitamin K (protein C,

S, factors II, VII, IX, X)

PTT PT/INR

Thrombin → Fibrin → Clot

Medication/Class Mechanism of Action Adverse effects Dosing Contraindications

Warfarin (coumadin)

Vitamin K antagonist Major bleedingTissue necrosis

2-10mg daily (adjusted per INR)

Pregnancy

Heparin (unfractionated)

Inactivates thrombin HIT 5000u BID-TID Hx of HIT

Low Molecular Weight Heparin (LMWH)

Factor Xa inhibitor Bruising, peripheral edema

30-40mg once-twice daily (enoxaparin)

Hx of HITCrCl < 15 mL/min

Direct Oral Anticoagulants (DOACs)

Factor Xa inhibitorsThrombin inhibitor

Bruising 2.5-5mg BID (apixiban)10-20mg daily (rivaroxaban)75-150mg BID (dabigitran)

Drug intolerance

Aspirin Inhibits platelet aggregation

Hypersensitivity, GI bleed, renal insufficiency, nasal polyps

75mg - 325mg daily Drug intolerance

Clopidogrel (Plavix)

Inhibits platelet aggregation

Bruising 75mg daily Drug intolerance

INR targets● INR 2.0 - 3.0 ● Exceptions:

○ Aortic mechanical valve + risk factors (a fib, prior thromboembolism, hypercoagulable conditions, LV dysfunction)

○ Mechanical mitral valve → 2.5 - 3.5

INR Goal

Does the patient have a mechanical

heart valve?

Yes No

Mitral Aortic INR 2.0 - 3.0

INR 2.5 - 3.5 Do they have any of the following:- Atrial fibrillation- LV dysfunction- Previous thromboembolism- Hypercoagulable state

Yes NoINR 2.5 - 3.5 INR 2.0 - 3.0

What impacts Coumadin dosing?

Antibiotics

Diet

Systemic disease

Antidepressants

Anti-inflammatoriesAnti-platelet agents

Alternative remedies/foods

Bariatric surgeryAlcohol

Medication/Class Mechanism of Action Adverse effects Dosing Contraindications

Warfarin (coumadin)

Vitamin K antagonist Major bleedingTissue necrosis

2-10mg daily (adjusted per INR)

Pregnancy

Heparin (unfractionated)

Inactivates thrombin HIT 5000u BID-TID Hx of HIT

Low Molecular Weight Heparin (LMWH)

Factor Xa inhibitor Bruising, peripheral edema

30-40mg once-twice daily (enoxaparin)

Hx of HITCrCl < 15 mL/min

Direct Oral Anticoagulants (DOACs)

Factor Xa inhibitorsThrombin inhibitor

Bruising 2.5-5mg BID (apixiban)10-20mg daily (rivaroxaban)75-150mg BID (dabigitran)

Drug intolerance

Aspirin Inhibits platelet aggregation

Hypersensitivity, GI bleed, renal insufficiency, nasal polyps

75mg - 325mg daily Drug intolerance

Clopidogrel (Plavix)

Inhibits platelet aggregation

Bruising 75mg daily Drug intolerance

Transitioning between anticoagulants

Anticoagulation Updates

Case 1KF is a 76 yo M with PMHx of HLD, HTN who recently was hospitalized following a fall on the ice and resulting hip fracture. He presented to the emergency department with left calf swelling that he noticed starting 2-3 days ago. HR 80s, BP 120/78, O2 99% on room air. EKG with normal sinus rhythm. Venous dopplers positive for DVT. According to the 2016 CHEST guidelines, which agent is recommended first line for treatment of the first episode of a provoked DVT/PE?

A) WarfarinB) LMWHC) ClopidogrelD) Apixaban

2016 CHEST Guidelines● DOACs - first line treatment of non-cancer associated provoked or

unprovoked VTE over vitamin K antagonists (2B) or LMWH (2C) ● LMWH - first line treatment of cancer-associated provoked or unprovoked

VTE over DOACs (2C) or vitamin K antagonists (2B)● Low-risk patients with subsegmental PE do not always require

anticoagulation

2014/2016 ACC/AHA Guidelines on ASA/DAPT● ASA

○ Heart valve replacement (mechanical or bioprosthetic)○ Primary prevention of CVD○ Secondary ischemic stroke prevention

● DAPT○ Bare metal stents → 1 month○ Coronary artery stenting (DES) → 6 months○ Stenting after MI → 12 months

Perioperative anticoagulation

Case 2DJ is a 64 yo F with PMHx of T2DM, atrial fibrillation on eliquis, HTN, HLD, bilateral knee osteoarthritis that you see in clinic for her annual physical exam and pre-op clearance. How long (ideally) should DJ’s eliquis be held prior to this elective procedure?

A) 24 hoursB) 48 hours C) 72 hoursD) It should be continued through the procedure

Perioperative anticoagulation● Recommendation is to delay elective surgery if:

○ Less than 6 months since PCI/DES○ Less than 12 months since ACS○ Less than 3 months since stroke

● Assess procedural bleeding risk○ Low → continue anticoagulation & ASA○ Moderate-high → interrupt

Risk stratification

CHADS2VASC & HASBLED

Perioperative anticoagulation● DOACs should be held for 48hr prior to surgery

○ Neuraxial anesthesia - 72hr due to risk for spinal hematoma

● Aspirin/anti-platelet agents○ Hold 5-7 days prior to surgery ○ If prior PCI/DES > 6 months → continue ASA through procedure○ If prior PCI/DES < 6 months → ASA monotherapy, resume plavix ASAP following

procedure

● Coumadin○ Hold for 5 days prior to OR

● LMWH/unfractionated heparin (bridging)○ Hold ~24hr prior to OR/hold 4-5hr prior to OR

Sunday Monday Tuesday Wednesday Thursday Friday Saturday Sunday

Last dose of Coumadin Surgery Restart

coumadin

Bridge (?)

Sunday Monday Tuesday Wednesday Thursday Friday Saturday

Last dose of DOAC Surgery Restart

DOAC

Sunday Monday Tuesday Wednesday Thursday Friday Saturday

Last dose of DOAC Surgery Restart

DOAC

Coumadin

DOAC - Low bleeding risk

DOAC - High bleeding risk

To Bridge or not to Bridge● Do not bridge atrial fibrillation (2015 BRIDGE)

○ Exceptions: CHA2DS2Vasc 7+ or embolic event within 3 months

● Mechanical valves warrant bridging (2014 ACC guidelines) ○ Exceptions: low risk aortic valves

● Do not bridge DOACs (2018 PAUSE)● Do not always need to bridge prior VTE

● Recent VTE or stroke (within 3 months) ● Active malignancy● Severe thrombophilia (antiphospholipid antibody syndrome) ● Mechanical valve● Atrial fibrillation with high CHA2DS2Vasc

Resumption of anticoagulation (post-procedure)● Coumadin

○ Resume the evening of/day after surgery (12-24hr) and monitor INR○ Requires a minimum of 5 days of overlap with parenteral anticoagulants (heparin/LMWH)

■ Monitor until INR is in targeted therapeutic range for >24hr

● LMWH/unfractionated heparin - therapeutic○ Resume 24hr after surgery

● DOACs provide more immediate anticoagulation ○ Resume 24hr after surgery

One additional consideration - Neuraxial Anesthesia● Prophylactic-dose LMWH

○ Wait at least 10-12hr after last dose of lovenox for placement of epidural○ Wait at least 6-8hr after epidural catheter removal to resume

● Therapeutic-dose LMWH○ Wait at least 24hr after last dose of lovenox for placement of epidural○ Wait at least 24hr after epidural catheter removal to resume

Reversal

Case 3WJ is a 68 year old male with PMHx of ESRD on HD, valvular atrial fibrillation on coumadin who was sent in by his outpatient coumadin clinic for a supratherapeutic INR and concern for rectal bleeding at home. In the ED, EKG confirms that he is in atrial fibrillation with HR 110s, BP 130/80s. FOBT is negative, you note external hemorrhoids on exam. INR repeated in the ED: 5.2. What next step would you take?

A) Hold today’s dose, repeat INR overnightB) IV Vitamin K, repeat INR C) PO Vitamin K, repeat INRD) FFP, repeat INR

Indications for reversal● In patients without significant bleeding

○ INR supratherapeutic but <4.5 → decrease/hold dose, resume at lower dose○ INR 4.5 - 10 → hold 1-2 doses, resume at lower dose ○ INR >10 → hold dose, administer vitamin K (PO), resume at lower dose

● In patients with concern for bleeding, options include: ○ PO/IV vitamin K○ FFP○ Recombinant Factor VIIa ○ Prothrombin complex concentrate (PCC - 3F & 4F)○ Factor VIII inhibitor bypass activity

Reversal of warfarin-induced bleed

Reversal agents● Heparin/LMWH

○ Protamine (unfractionated heparin > LMWH)

● Reversal in DOACs○ Idarucizumab → dabigatran○ Andexxa (andexanet alpha) → rivaroxaban & apixiban

Anticoagulation in COVID

Case 4JR is a 32yo M with no significant PMHx who was hospitalized for COVID PNA. His oxygen requirement decreases during his hospitalization and he is stable for discharge. He has been reading Dr. Haines’ book during his hospitalization and while getting ready for discharge, he asks whether he needs VTE prophylaxis after leaving the hospital. What do you think?

A) SureB) Not indicated

Anticoagulation in COVID

Anticoagulation in COVID

How this should change our practice● Bleeding risk assessment should be performed at each visit for patients

on anticoagulation.● When discussing medications on hospital discharge - consider DOACs

over coumadin. ● Communicate with surgical teams - particularly during visits for pre-op

clearance and keep an open line of communication with surgical consult teams while in the hospital.

● Communicate with pharmacy to appropriately adjust dosing for kidney function.

Take Home Points● Anticoagulation, both inpatient & outpatient, requires careful patient

monitoring and follow up is important! ● Monitor for changes to a patient’s medication list.● There is no one-size-fits-all when it comes to decisions for perioperative

anticoagulation.● Consider VTE prophylaxis in COVID patients when discharging from the

hospital.

ReferencesBoundless. “Boundless Anatomy and Physiology.” Lumen, courses.lumenlearning.com/boundless-ap/chapter/hemostasis/.

Doherty JU, Gluckman TJ, Hucker WJ, Januzzi JL Jr, Ortel TL, Saxonhouse SJ, Spinler SA. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. doi: 10.1016/j.jacc.2016.11.024. Epub 2017 Jan 9. PMID: 28081965.

Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, Davila-Roman VG, Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky BF, Wijeysundera DN; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014 Dec 9;64(22):e77-137. doi: 10.1016/j.jacc.2014.07.944. Epub 2014 Aug 1. PMID: 25091544.

Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report [published correction appears in Chest. 2016;150(4):988]. Chest. 2016;149(2):315–352.

Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115. doi: 10.1016/j.jacc.2016.03.513. Epub 2016 Mar 29. PMID: 27036918.

ReferencesOrtel TL. Perioperative management of patients on chronic antithrombotic therapy. Blood. 2012;120(24):4699-4705. doi:10.1182/blood-2012-05-423228

UpToDate, www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants.

Watto, M & O’Glasser, A (Hosts). (2019, September 23). Dominate Perioperative Medication Management (No 174). [Audio Podcast Episode]. https://thecurbsiders.com/podcast/174-periop

Wigle, Patricia, et al. “Anticoagulation: Updated Guidelines for Outpatient Management.” American Family Physician, 1 Oct. 2019, www.aafp.org/afp/2019/1001/p426.html.

Yee J, Kaide CG. Emergency Reversal of Anticoagulation. West J Emerg Med. 2019;20(5):770-783. Published 2019 Aug 6. doi:10.5811/westjem.2018.5.38235

Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in the emergency department. West J Emerg Med. 2011;12(4):386-392. doi:10.5811/westjem.2011.3.2051

Questions?

Warfarin (coumadin)● Vitamin K antagonist● Indications:

○ Valvular atrial fibrillation, mechanical valve

● Contraindications: ○ Pregnancy○ Unsupervised & potentially noncompliant patients

● Adverse effects:○ Tissue necrosis (<0.1%), compartment syndrome○ Major bleeding (<5%)

Heparin (unfractionated)● Inactivates thrombin, prevents conversion of fibrinogen to fibrin ● Indications:

○ Anticoagulation in CKD/HD patients, ACS, bridging

● Contraindications: ○ Severe thrombocytopenia, history of HIT○ Recommend not to initiate drip if appropriate levels cannot be monitored

● Adverse effects: ○ Thrombocytopenia (+/- HIT)

Low-molecular weight heparin (ex: lovenox)● Factor Xa inhibitor● Indications:

○ Active malignancy, VTE

● Contraindications: ○ History of HIT○ CrCl < 15 mL/min

● Adverse effects: ○ Peripheral edema

Direct oral anticoagulants (dabigatran)● Direct thrombin inhibitor ● Indications:

○ Non-valvular atrial fibrillation, DVT/PE (tx & prophylaxis), stroke prevention

● Contraindications: ○ Drug intolerance

● Adverse effects: ○ Bruising

Direct oral anticoagulants (apixaban, rivaroxaban)● Inhibition of factor Xa● Indications for use:

○ Non-valvular atrial fibrillation, DVT/PE (tx & prophylaxis), stroke prevention

● Contraindications: ○ Drug intolerance

● Adverse effects: ○ Bruising

Aspirin● Inhibits COX-1 & 2 enzymatic activity; inhibits formation of thromboxane

A2 which inhibits platelet aggregation● Indications for use:

○ ACS, TIA, colorectal cancer, preeclampsia, heart valve

● Contraindications: ○ Drug intolerance

● Adverse effects: ○ GI bleed, ASA sensitivity, Reye’s syndrome, renal insufficiency

Plavix (clopidogrel)● Inhibition of platelet aggregation● Indications for use:

○ ACS, stroke/TIA

● Contraindications: ○ Allergy/intolerance

● Adverse effects: ○ Bruising