Perioperative management of antithrombotic therapy

Ext. Phatcharapol Udomluck Medical 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 signicant 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

2009 by Cleveland Clinic

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

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, di 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)