1. Perioperative management of
antithrombotic therapy
Ext. Phatcharapol Udomluck
Medical student
Naresuan university

2. 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

3. 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

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

5. 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

6. ( Prior MI, PAD, Aortic plaque )

9. ASSESSMENT OF THROMBOTIC RISK
• Mechanical heart valves and venous thromboembolism

10. 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

11. 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

12. 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

13. Assessment of
Periprocedural bleeding risk
• Major bleeding depends on procedure
– High-risk : Major bleed
• intracranial, intraspinal, intraocular, retroperitoneal, int
rathoracic, 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

15. 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

16. Low – intermediate (HAS-BLED 0-2)

17. High risk (HAS-BLED score >= 3)

20. Bridging anticoagulant therapy

21. 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

22. Low risk  Stop anticoagulant but not start bridging anticoagulant

23. 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”)

24. 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

25. After procedure : Start Oral anticoagulant when keep
desired INR level for 3 day
Y. Chintammit : Update in internal medicine
2009 : 343 – 349

26. SC
IV UFH : Keep aPTT 1.5 – 2 x control
Y. Chintammit : Update in internal medicine
2009 : 343 – 349

29. 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

30. 2011 Clinical Practice Guide on Anticoagulant Dosing and
Management of Anticoagulant-Associated Bleeding Complications in Adults

31. 2011 Clinical Practice Guide on Anticoagulant Dosing and
Management of Anticoagulant-Associated Bleeding Complications in Adults

32. 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

33. 2011 Clinical Practice Guide on Anticoagulant Dosing and
Management of Anticoagulant-Associated Bleeding Complications in Adults
* heparin-induced
thrombocytopenia

34. 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

35. Perioperative management of
antiplatelet therapy

36. 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

37. 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)

38. 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

40. 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

41. 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

42. Recommendation of ACCP 2012

43. 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

44. 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)

45. 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)

46. 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)

47. 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

51. 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

53. GRACE

54. 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)