Everything

Anticoagualtion Heather Kertland

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By the end of the session you should be able to:

1. Identify which patient populations should be

considered for bridging

2. Review the current peri-operative

management of anticoagulation

3. Selection an anticoagulant for a patient with

renal dysfunction

4. Selection an anticoagulant for patient with

heparin-induced thrombocytopenia

Learning Objectives

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Do you need to bridge?

3 N Engl J Med 2015;373:823-33 DOI:10.1056/NEJMoa1501035

• N=1884

• A fib/flutter requiring surgery/procedure

– Excluded cardiac, intracranial, intraspinal surgery

– Mech heart valve, stroke/systemic embolism is last 12 weeks excluded

• Warfarin interruption versus interruption and bridging with dalteparin 100

units/kg q12H

• Surgeries: orthopedic 30 – 33%, urologic 22 – 27%, general sx 15 – 17%

BRIDGE trial

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No bridging Bridging

Stroke/TIA/systemic embolism

0.4% 0.3%

Major bleeding 1.3% 3.2%

Minor bleeding 12% 20%

• CHADS2 5/6 – 2.7 – 3.4%

Bruise-Control Trial

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• Concerns of pocket hematoma with anticoagulation peri-

device insertion

• Randomized, single-blind trial

• Patients with annual thromboembolism risk < 5%

• Continue warfarin (INR < 3) versus bridging

anticoagulation

• Outcome: clinically significant pocket hematoma and

bleeding

• Stopped after 2nd interim analysis (668 out of planned 984

patients)

Bruise-Control trial

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• Population

Population -

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• Significant hematoma

–Continued warfarin 3.5%

–Bridged 16%

• Embolic events

– Continued warfarin - 2 patients

•INR 1 – 1.2 on day of surgery

–Bridged - 0

• Identified risk factor for hematoma formation

–Use of ASA

Results

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• Similar to Bruise but on DOAC

–All 3 agents equally represented

• Continued arm – took dose the morning of surgery

• Interrupted arm – 2 days before surgery (longer if

renal dysfunction)

• Drugs reinitiated at least 24 hours post-procedure

• Trial stopped early – 590/846 patients enrolled

BRUISE-Control 2

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14 CCS 2016

guidelines

Appendix of 2017 ACC Expert Consensus

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Patients with

• Thromboembolism during past interruptions or while on therapeutic

anticoagulation

• stroke/TIA in past 3 months

• Recent (within 1 month) evidence of mural thrombus or left atrial appendage

clot

• Mitral mechanical valve

• Older caged ball or tilting disc mechanical valves

• VTE in past 3 months

• VTE and hypercoagulable statin (e.g., antiphospholipid antibody syndrome,

Protein C or S deficiency or antithrombin 3 deficiency)

Circ Cardiovasc Qual Outcomes. 2016;9:64-67.

DOI: 10.1161/CIRCOUTCOMES.115.002430

Who should be bridged?

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Who should be bridged

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www.thrombosiscanada.ca

March 25, 2019

CCS – 2-16 a fib guidelines

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Recommendation Supporting Evidence

Interruption of anticoagulant therapy, particular for vitamin K

antagonists (VKAs), in a patient with AF/AFL is not necessary for

most procedures with a low risk of bleeding (i.e. cardiac device

implantation, dental procedures).

BRUISE-CONTROL trial (7)

For patients planning to interrupt warfarin therapy prior to a

procedure, bridging therapy with LMWH or unfractionated

heparin (when INR below therapeutic) only in patients at high

risk of thromboembolic events (CHADS2 ≥ 4, mechanical heart

valve, recent stroke/TIA, rheumatic heart disease).

BRIDGE trial (8)

No bridging for non-valvular AF patients receiving NOACs

requiring interruption of anticoagulation.

Perioperative Dabigatran Study, ORBIT-AF, and Dresden NOAC

Registries (10-12)

Table 1. CCS 2016 Periprocedural Anticoagulation Recommendations

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LMWH and renal dysfunction

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Enoxaparin

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Renal Function Accumulation T ½

Normal > 80 mL/min 4.4 hrs

Mild 50 – 79 mL/min 17% 5.4 hrs

Moderate 30 – 49 mL/min 31% 6.4 hrs

Severe < 30 mL/min 44% 8.0 hrs

Hulot et al Clin Pharmacol Ther 2005;77:542-52.

Sunnybrook guideline

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Based on 1.5 mg/kg q24 if CrCl > 30 mL/min

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B. Subsequent tinzaparin dosing nomogram Tinzaparin doses may be adjusted on days 3 and 5 (+/- 1 day) based on the trough anti-Xa level. Tinzaparin doses will be rounded up or down to the nearest 1000 IU. The following dosing nomogram will be used:

For example, a 70-kg patient who received tinzaparin 12,250 IU (175 IU/kg x 70 kg) on days 1 and 2 has an anti-Xa measurement of 0.72 IU/mL on day 3. This patient would receive 50% of their initial dose on days 3 and 4:

Calculated tinzaparin dose: 12,250 IU x 0.5 = 6,125 IU Administered tinzaparin dose (rounded to the nearest 1000 IU) = 6,000 IU

On day 5, their anti-Xa measurement is 0.65 IU/mL. This patient would then receive 75% of the previous dose for day 5: Calculated tinzaparin dose: 6,000 IU x 0.75 = 4,500 IU (pre-filled syringe at this dose).

Trough anti-Xa level (IU/mL) Tinzaparin dose (175 IU/kg)

< 0.50

No dose adjustment, continue with current dose

0.50 – 0.69

75% of the previous dose

0.70 – 0.99

50% of the previous dose

≥ 1.00

Hold the next dose, resume the following day at 50% of previous dose

APPENDIX D continued

Tinzaparin – trough levels

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Target 4 hour levels

Twice daily dalteparin 0.8 – 1.2

Rivaroxaban dosing

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US: 15 – 50 mL/min – same a Canadian

Apixaban dosing

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US dosing:

DVT – no dosing adjustment required

A fib – ESRD & HD - 5 mg BID*

- Based on kinetic studies

Obesity - Enoxaparin

31 Annals Pharmacotherapy 2018;52:898-909

Heparin-induced thrombocytopenia

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ASH VTE guidelines

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ASH gudelines

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• Apixaban 10 mg BID x 7 days (and platelets

greater than 150) then 5 mg BID

• Rivaroxaban 15 mg BID x 21 days (and platelets

greater than 150) then 20 mg daily

• Fondaparinux

–Weight based dosing

• Argatroban

–aPTT 2 – 3 x baseline aPTT

HIT dosing

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Alternative Heparin dosing

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• 333 units/kg subcut X 1 then 250 units/kg q12H

Questions

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