This document discusses the perioperative management of antithrombotic therapy. The goals are to prevent thromboembolic events like strokes while reducing the risk of major hemorrhage during surgery. It assesses thrombotic risk based on the type of anticoagulation and bleeding risk scores. It provides guidance on bridging anticoagulation during surgery and reversing anticoagulants. It also discusses perioperative management of antiplatelet drugs like aspirin and clopidogrel based on surgery type and risk of cardiovascular events.

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)