Perioperative management of antithrombotic therapy

Ext. Phatcharapol UdomluckMedical student

Naresuan university

Antithrombotic therapy

• Long-term anticoagulation therapy for the prevention of thromboembolism due to – Atrial fibrillation– Placement of a mechanical heart-valve prosthesis– Venous thromboembolism

• Dual antiplatelet therapy (combination treatment with aspirin and a thienopyridine) after the placement of a coronary-artery stent has dramatically increased

Perioperative management of antithrombotic therapy

Goal • Prevent thromboembolic (TE) events

– Arterial TE : Prosthetic valve thrombosis (5.9-64.7%) , Cardioembolic stroke (fatality 4.2-14.9)

– Venous TE : DVT, PE (fatality 26.4)

• Reduced major hemorrhage in the periprocedural period

http://www.drtedwilliams.net/Dr Ted Williams, PharmD education (2009)

ASSESSMENT OF THROMBOTIC RISK

• Valvular atrial fibrillation– Severe valvular heart disease (mechanical valvular

prosthesis or mitral-valve repair) : high risk for TE

• non-valvular atrial fibrillation– The CHA 2 DS 2 -VASc score

( Prior MI, PAD, Aortic plaque )

ASSESSMENT OF THROMBOTIC RISK

• Mechanical heart valves and venous thromboembolism

ASSESSMENT OF THROMBOTIC RISK

Cancer– Increased risk of periprocedural thrombosis

• Cancer-specific prothrombotic activity, hormonal therapy, angiogenesis inhibitors, radiotherapy, and the presence of indwelling central venous catheters

– Increased risk of bleeding• Prophylactic agents for the prevention of venous

thromboembolism, chemotherapy-related hepatic and renal dysfunction and thrombocytopenia

ASSESSMENT OF THROMBOTIC RISK

Coronary stents• Some patients with coronary stents may require dual

antiplatelet therapy

• Premature discontinuation of antiplatelet therapy in anticipation of invasive procedure may lead to stent thrombosis and precipitation of myocardial infarction

• Rate of 50% or higher

Coronary stent

Bare-metal stent• Risk of thrombosis is

highest within 6 Wks after placement of stent

• Dual antiplatelet required – ASA(165-325 mg/day) : 1 mo– Clopidogrel : at least 1 mo

and Up to 12 mo

Drug-eluting stent• Risk of thrombosis is

highest within 3-6 mo after placement of stent

• Dual antiplatelet required – ASA(165-325 mg/day)

• Sirolimus 3 mo• Paclitaxel 6 mo

– Clopidogrel : at least 12 mo

Assessment of Periprocedural bleeding risk

• Major bleeding depends on procedure– High-risk : Major bleed

• intracranial, intraspinal, intraocular, retroperitoneal, intrathoracic, or pericardial bleeding

• Additional Risk factors– Residual effects of antithrombotic agents

– Active cancer

– Chemotherapy

– History of bleeding

– Reinitiation of antithrombotic therapy within 24 hours after the procedure

HAS-BLED risk score

• SBP > 160 mmHg• Chronic dialysis or renal transplantation or serum

creatinine ≥ 200 mmol/L• Chronic hepatic disease (e.g. Cirrhosis) or

biochemical evidence of significant hepatic derangement

• Previous bleeding history and/or predisposition to bleeding, e.g. Bleeding diathesis, anaemia

• Concomitant use of drugs, such as antiplatelet agents, NSAIDs

Low – intermediate (HAS-BLED 0-2)

High risk (HAS-BLED score >= 3)

Bridging anticoagulant therapy

Assessment tool for identifying patient-specific and surgical risk factors for patients on anticoagulation therapy who are undergoing elective surgery

JAFFER A K Cleveland Clinic Journal of Medicine 2009;76:S37-S44©2009 by Cleveland Clinic

Low risk Stop anticoagulant but not start bridging anticoagulant

Recommend for Warfarin use

• Stop oral anticoagulant 5 day before invasive procedure – Keep INR <1.5

• If follow up INR > 1.5 in 1-2 day before invasive procedure– Vitamin K 1-2 mg

• If Continue Warfarin : Keep INR approximately 2.5

• Urgent operative procedure– Oral or IV Vitamin K 2.5-5.0 mg

• Emergency operative procedure– FFP + Low dose (IV or Oral) Vitamin K

• Mechanical heart valve – Only use FFP ( NOT use Vitamin K “Warfarin resistance”)

Bridging anticoagulant

• Recommend for Moderate to High risk TE– Start when INR <2– Therapeutic dose SC LMWH or IV UFH– If GFR < 30 IV UFH is preferred

• Stop bridging before invasive procedure– Therapeutic SC LMWH or SC UFH : 12-24 hr before

procedure (Use half dose in Morning last dose)– IV UFH : 4-6 hr before procedure

• Half life 60 – 90 min , Dissipate after discont. 3 – 4 hr

After procedure : Start Oral anticoagulant when keep desired INR level for 3 day

Y. Chintammit : Update in internal medicine 2009 : 343 – 349

SC

IV UFH : Keep aPTT 1.5 – 2 x control

Y. Chintammit : Update in internal medicine 2009 : 343 – 349

Reversal of anticoagulant

Reversible anticoagulant agent

• Warfarin– Vitamin K and Fresh frozen plasma– Prothrombin complex concentrates preferred in …

• CHF, Valvular heart disease, Renal failure• Volume overload from Large volume infusion of FFP

• Heparin– Protamine can reverse the action

• UFH : Completely reversal• LMWH : Partial reversal

2011 Clinical Practice Guide on Anticoagulant Dosing and Management of Anticoagulant-Associated Bleeding Complications in Adults

2011 Clinical Practice Guide on Anticoagulant Dosing and Management of Anticoagulant-Associated Bleeding Complications in Adults

Reversal warfarin

• ACCP (2008) guidelines recommends • Oral doses of vitamin K

– 1-2.5 mg for an INR between 5 and 9 – 2.5-5 mg for INR ≥ 9, no significant bleeding– 10 mg for serious bleeding and elevated INR

2011 Clinical Practice Guide on Anticoagulant Dosing and Management of Anticoagulant-Associated Bleeding Complications in Adults

* heparin-induced thrombocytopenia

Reversal of anticoagulant

Nonreverssible anticoagulant agent – Reliable reversibility has not been proved

• Direct factor Xa inhibitors (Rivaroxaban)– Prothrombin complex concentrates (contain factor II, VII, IX,

X and protein C ,S)

• Direct thrombin inhibitor (Dabigatan)– Life-threatening bleeding that cannot be managed with

supportive care and local hemostatic measures

– Hemodialysis or charcoal hemoperfusion can be considered

Perioperative management of antiplatelet therapy

Antiplatelet

• Antiplatelet drugs (irreversible)– ASA, clopidogrel, ticlopidine, and prasugrel– For each day after interruption 10% to 14% of

normal platelet function is restored; later, it takes 7 to 10 days for an entire platelet pool to be replenished

Antiplatelet

• Antiplatelet drugs (reversible)– Dipyridamole, Cilostazol, and NSAIDs

• Dipyridamole, a pyridopyrimidine derivative with antiplatelet and vasodilator properties, has a half-life of 10 h

• Cilostazol, a phosphodiesterase inhibitor with anti-platelet and vasodilator properties, has a half-life of 10 h

• NSAID have half-lives that vary from – 2 to 6 h (ibuprofen, ketoprofen, indomethacin)– to 7 to 15 h (celecoxib, naproxen, difl unisal)– to . 20 h (meloxicam, nabumetone, piroxicam)

Antiplatelet

• Patients who were receiving a VKA and ASA typically resumed ASA at the same time as the VKA, which was within 24 h after surgery

Schematic of different therapeutic options for inhibition of platelet P2Y12 receptor.

Ferreiro J L , and Angiolillo D J Circ Cardiovasc Interv 2012;5:433-445

Copyright © American Heart Association

Assessment

• Optimal preoperative management of patients with coronary artery stents depends on many factors

• Relative risks and benefits of stopping versus continuing antiplatelet therapy – Identification of patients at high risk for a perioperative event

after cessation of antiplatelet therapy– Identifi cation of patients at high risk of bleeding

• The risk of perioperative bleeding increases when two or more antiplatelet agents are used

Recommendation of ACCP 2012

Minor surgery

• In patients who are receiving ASA for the secondary prevention of cardiovascular disease and are having minor dental or dermatologic procedures or cataract surgery – suggest continuing ASA around the time of the

procedure instead of stopping ASA 7 to 10 days before the procedure

Non-cardiac surgery

• In patients at moderate to high risk for cardiovascular events– suggest continuing ASA around the time of surgery

instead of stopping ASA 7 to 10 days before surgery (Grade 2C)

• In patients at low risk for cardiovascular events– suggest stopping ASA 7 to 10 days before surgery instead

of continuation of ASA (Grade 2C)

CABG surgery

• suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C)

• In patients who are receiving dual antiplatelet drug therapy and require CABG surgery– suggest continuing ASA around the time of surgery and stopping

clopidogrel/prasugrel 5 days before surgery instead of continuing dual antiplatelet therapy around the time of surgery (Grade 2C)

Patients with Coronary Stents having Surgery

• Surgery for at least 6 weeks after placement bare-metal stent • Surgery for at least 6 months after placement drug-eluting

stent instead of undertaking surgery within these time periods (Grade 1C)

• In patients who require surgery within 6 weeks of placement of a bare-metal stent or within 6 months of placement of a drug-eluting stent– suggest continuing dual antiplatelet therapy around the time of

surgery instead of stopping dual antiplatelet therapy 7 to 10 days before surgery (Grade 2C)

Resumption of antiplatelet

• Clopidogrel administered at maintenance doses has a delayed onset of action, and treatment can therefore be reinitiated within 24 hours after the procedure

• Treatment with other antiplatelet agents, including aspirin, can be reinitiated within 24 hours

• Caution when reinitiating treatment with prasugrel or ticagrelor because of – their rapid onset of action, potent antiplatelet inhibition, and

the lack of agents to reverse their effects

Canadian Cardiovascular Society (CCS) class of angina

• Class I – Angina only during strenuous or prolonged physical activity

• Class II – Slight limitation, with angina only during vigorous physical activity

• Class III – Symptoms with everyday living activities, i.e., moderate limitation

• Class IV – Inability to perform any activity without angina or angina at rest, i.e., severe limitation

GRACE

Killip class

• I: no clinical signs of heart failure • II: crackles, S3 gallop and elevated jugular venous

pressure • III: frank pulmonary oedema • IV: cardiogenic shock - hypotension (systolic < 90

mmHg) and evidence of peripheral vasoconstriction (oliguria, cyanosis, sweating)