Perioperative Management of Anticoagulation

Transcription

1 Perioperative Management of Anticoagulation Presented By: Nibal R. Chamoun, PharmD, BCPS Clinical Assistant Professor, Clinical Coordinator Lebanese American University, School of Pharmacy Presented at: 25 TH Annual Congress on November

2 Outline 1. Identify risk factors associated with perioperative bleeding versus thromboembolism 2. Discuss the decision pathway to consider in perioperative management of anticoagulation 3. Recognize key factors linked to the appropriate timing to withhold oral anticoagulants 4. Identify patients who warrant bridging of parenteral anticoagulation 5. Identify the appropriate timing to resume anticoagulation post operatively 6. Summarize the perioperative management of vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) 18/12/2017 2

3 Definitions and Abbreviations Definitions: - Perioperative: around the time of a surgery (before and after surgery) - Bridge anticoagulant therapy is the administration of a shortacting parenteral anticoagulant during the peri-operative period, when the patient is not taking chronic oral anticoagulant. Abbreviations: - OACs: Oral anticoagulants - DOACS: Direct oral anticoagulants - VKA: Vitamin K antagonists - TE: Thromboembolic Risk - DVT: Deep venous thrombosis - PE: Pulmonary embolism - VTE: Venous thromboembolism, including DVT & PE 18/12/2017 Circulation. 2012;125(12):e

4 Illustration of Perioperative Management of Anticoagulation Oral Anticoagulation Stop OAC before Surgery But what do we do in the meantime?? We give parenteral Anticoagulation that can be safely stopped before surgery Stop the parenteral anticoagulant before surgery Images taken from figures and multimedia from NEJM So we can safely operate with minimal bleeding 4

5 Background Patients receiving chronic oral anticoagulation for a variety of indications such as DVT, PE, Atrial Fibrillation, Secondary Prevention of Stroke, Mechanical Heart Valves Chronic oral anticoagulation includes: - VKAs (acenocoumarol, hydroxycoumarol or fluindione) - DOACS (rivaroxaban, apixaban and dabigatran) Around 15-20% of such patients require interruption of anticoagulation per year The decision of whether or not to bridge with parenteral agents is a clinical dilemma especially in lieu of minimal evidence. Circulation. 2012;126: /12/2017 Circulation. 2014;129: J Am Coll Cardiol 2015;66:

6 Background Guidelines on the perioperative management of anticoagulation: - American Heart Association, American College of Cardiology, Heart Rhythm Society - American College of Chest Physicians ** Recommendations are based on observational studies and expert opinion with minimal primary literature. Guideline consensus on 3 important principles: 1. OAC should not be interrupted for procedures with low bleeding risk. 2a. Patients at high risk for TE>>>bleeding risk need bridging 2b. Patients at low risk for TE or Bleeding risk >>>>TE no bridging 3. Intermediate- TE- risk cases should be managed individually based on patient- and procedure-specific risks for bleeding and TE. 18/12/2017 Chest 2012;141:e326S 50S. J Am Coll Cardiol 2014; 64:e

7 Step 1 in Perioperative Management of Anticoagulation- ASKING THE RIGHT QUESTIONS Asking the right questions helps gather important data for: - Improved communication - Informed decision making Key questions for pharmacists to ask: - Why are you taking chronic oral anticoagulation? - Who prescribed this medication to you? - How long have you been on it? - Have you ever had to stop this medication before? If yes for how long? 18/12/2017 7

8 Asking the right questions: How it helps Questions Patient Answers Is it a MUST to give BRIDGE THERAPY perioperatively?? (yes/no/not sure ) Why are you taking chronic oral anticoagulation Who prescribed this medication to you? Have you ever had to stop this medication before? If yes for how long? Why are you taking chronic oral anticoagulation I have a blood clot in my lungs (Pulmonary Embolus) that was found last week. My oncologist, but I m not sure why. I have a history of clots I think Yes, onetime I had to stop for a dental implant however 4 days later I went to the hospital with a clot in my leg. I had a blood clot in my lungs 4 years ago after having a huge car accident. Doctor told me it s from the accident but I don t have any other clotting abnormalities. 18/12/ YES YES / Not sureconfirm with oncologist YES NO

9 Case 1 HM is a 46 yo woman with a past medical history of atrial fibrillation and HTN Home medications include: - Bisoprolol 5mg po daily - Acenocoumarol 2mg po daily, most recent INR on was 2.2 (INR goal is 2-3) Her dentist informs her that she is going to undergo dental extraction on Which of the following is the most appropriate perioperative management of her anticoagulantion? a) Discontinue acenocoumarol 4 days before procedure b) Discontinue acenocoumarol 4 days before procedure and start enoxaparin when INR is less than 2 c) No need to discontinue acenocoumarol because it is a low bleeding risk procedure d) No need to discontinue acenocoumarol because it is a procedure that can be done on anticoagulation, but do not take acenocoumarol in the morning of the procedure 18/12/2017 9

10 Which procedures require: No need for Interruption of OAC N.B: very important that the OAC is not at peak activity or higher end of the therapeutic range during the procedure. For DOACS, wait 12 or 24 h after the last intake, depending on their specific regimen dosing (once or twice daily). For VKA, make sure INR is on the lower end of the therapeutic range ~ INR=2 18/12/ J Am Coll Cardiol 2015;66: European Heart Journal Cardiovascular Pharmacotherapy (2015) 1, Some examples of procedures that can be done without interruption of DOACs include skin cancer removal, joint injection, cataract removal, or tooth extraction in which an adequate local haemostasis is commonly possible. 2 Very important to coordinate with the surgeon or physician performing the procedure. They might not accept to operate 10 with on OAC!

11 Case 1 HM is a 46 yo woman with a past medical history of atrial fibrillation and HTN Home medications include: - Bisoprolol 5mg po daily - Acenocoumarol 2mg po daily, most recent INR on was 2.2 (INR goal is 2-3) Her dentist informs her that she is going to undergo dental extraction on Which of the following is the most appropriate perioperative management of her anticoagulantion? a) Discontinue acenocoumarol 4 days before procedure b) Discontinue acenocoumarol 4 days before procedure and start enoxaparin when INR is less than 2 c) No need to discontinue acenocoumarol because it is a low bleeding risk procedure d) No need to discontinue acenocoumarol because it is a procedure that can be done on anticoagulation, but do not take acenocoumarol in the morning of the procedure 18/12/

12 Perioperative Management of Anticoagulation Bleeding Risk Factors 1) Procedure 2) Patient-specific Thromboembolic Risk Depending on Indication and History 18/12/

13 Risk factors associated with perioperative bleeding versus thromboembolism BLEEDING RISK 1. Patient specific risk factors 2. Procedure specific risk of bleeding (low, moderate or high) 18/12/2017 THROMBOEMBOLISM RISK 1. Indication specific risk factors - Mechanical Heart Valves Mechanical vs bioprosthetic Aortic or mitral - Atrial Fibrillation CHADS2 CHAS2VAS2C - Venous Thromboembolism Timing of VTE Dubois et al. Thrombosis Journal (2017) 15:14 Circulation. 2017;135(24). J Am Coll Cardiol 2014; 64:e

14 Thromboembolic Risk Stratification Perioperatively 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s (J Am Coll Cardiol 2015;66: ) 14

15 Procedure-related-bleeding risk (VKA) perioperatively Surgeries and Procedures at an increased risk of bleeding if on antithrombotic therapy around the perioperative time: - Urologic surgery - Pacemaker or device implantation - Colonic polyp resection, typically of large polyps (1-2cm) - Surgery and procedures in highly vascular organs (ex. kidney, liver, and spleen) - Bowel resection - Major surgery with extensive tissue injury (eg, cancer surgery, joint arthroplasty, reconstructive plastic surgery) - Cardiac, intracranial, or spinal surgery- high risk bleeding 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s 15

16 Procedure-related-bleeding risk (DOACS) perioperatively Minor interventions: - Skin cancer removal, joint injection, cataract removal, or tooth extraction in which an adequate local haemostasis is commonly possible. Minor surgery: - Endoscopy with biopsy; prostate or bladder biopsy; electrophysiological study or simple radiofrequency catheter ablation; angiography; pacemaker or ICD implantation. Major surgery: - Complex leftsided ablation; spinal or epidural anaesthesia; lumbar diagnostic puncture; thoracicsurgery; abdominal surgery; major orthopaedic surgery; liver biopsy; transurethral prostate resection; kidney biopsy. 18/12/2017 European Heart Journal Cardiovascular Pharmacotherapy (2015) 1,

17 Patient Specific Bleeding Risk Score HAS-BLED Score is utilized in patients with Atrial Fibrillation Only High bleeding score 3 Identify and treat modifiable bleeding risk factors European Heart Journal (2010) 31, Hosp Pract. 2011;39:41 54 Eur Heart J 2016 Oct 7;37(38):

18 Institutional Checklists for Perioperative Anticoagulation: Decision Algorithms - Development of institutional guidelines and hospital policies for the perioperative management of Anticoagulants (DOACs or VKA) - A checklist including all aspects of the particular procedure and the patient characteristics that may increase the risks of bleeding or thrombosis should be available 18/12/2017 The perioperative checklist 1. The Thrombo-embolic risk of the patient 2. The bleeding Risk of the patient 3. Time of stopping the OAC before an invasive procedure 4. Specific considerations for some invasive procedures 5. When should bridge therapy with parenteral anticoagulants be suggested?? 6. When should we stop bridge therapy prior to the procedure? 7. Resuming an OAC after an invasive procedure or surgery Europace. 2015;17: Faraoni Crit Care. 2015;19:203 18

19 Published Decision Algorithm: Perioperative Management of Anticoagulation 18/12/2017 VOL. 69, NO. 7, THE AMERICAN COLLEGE OF CARDIOLOGY 19

20 When to Interrupt OAC?? Appropriate Timing to Withhold Anticoagulation Perioperatively VKA Type of procedure Physician comfort INR level DOACS Type of procedure Renal function (Creatinine Clearance according to cockgroft gault equation) 18/12/

21 VKA Perioperative Management When to stop How to bridge: based on INR When to stop bridge prior to the procedure When to resume OAC after the procedure 18/12/

22 Case 2 CC is a 42 yo man with a factor V Leiden, history of DVT x2 and recently diagnosed with a Pulmonary Embolus 20 days ago. Wt= 80kg and CrCl=94ml/min Maintained on acenocoumarol at home (INR goal 2-3). He is scheduled for a major orthopedic surgery on at 9am. His doctor advised to stop acenocoumarol 4 days before surgery. His Surgery is in 2 days and today his INR is 1.7. How would you manage this patient perioperatively? a) INR is subtherapeutic so no need to give parenteral anticoagulation b) Start enoxaparin 80mg SC bid now and give the last dose of enoxaparin on at 9 am (24 hours before surgery) c) Start enoxaparin 80mg SC bid now and give the last dose of enoxaparin on at 9 pm (12 hours before surgery) 18/12/

23 Appropriate timing to STOP VKA Before the Procedure If patients need temporary interruption of a VKA before surgery, recommended to stop VKAs approximately 5 days before surgery(grade 1C). Half life of VKA: - Warfarin (hydroxycoumarol): hours - Sintrom (acenocoumarol ): 8 to 11 hours Based on this discontinue acenocoumarol 4 days before surgery 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s 23

24 Identifying Patients who require Bridge Therapy 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s (J Am Coll Cardiol 2015;66: ) 24

25 Bridging Dose Regimens high-dose regimen (therapeutic-dose ) - enoxaparin 1 mg/kg bid or 1.5 mg/kg daily - tinzaparin 175 International Units/kg daily - IV UFH to reach 1.5 to 2.5 times the control aptt low-dose regimen (prophylactic-dose) - enoxaparin 30 mg bid or 40 mg daily - UFH 5,000-7,500 International Units bid intermediate-dose regimen (between high- and low-dose regimens) - enoxaparin 40 mg bid 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s 25

26 When to stop bridging prior to surgery? - If using therapeutic-dose IV UFH, stop UFH 4 to 6 h before surgery (Grade 2C). - If using therapeutic-dose SC LMWH, administer the last preoperative dose of LMWH approximately 24 h before surgery (Grade 2C). Minimize bleeding intraoperatively 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s 26

27 Case 2 CC is a 42 yo man with a factor V Leiden, history of DVT x2 and recently diagnosed with a Pulmonary Embolus 20 days ago. Wt= 80kg and CrCl=94ml/min Maintained on acenocoumarol at home (INR goal 2-3). He is scheduled for a major orthopedic surgery on at 9am. His doctor advised to stop acenocoumarol 4 days before surgery. His Surgery is in 2 days and today his INR is 1.7. How would you manage this patient perioperatively? a) INR is subtherapeutic so no need to give parenteral anticoagulation b) Start enoxaparin 80mg SC bid now and give the last dose of enoxaparin on at 9 am (24 hours before surgery) c) Start enoxaparin 80mg SC bid now and give the last dose of enoxaparin on at 9 pm (12 hours before surgery) 18/12/

28 Resumption of Anticoagulant post surgery After surgery: - In patients who require temporary interruption of a VKA before surgery, resume VKAs approximately 12 to 24 h after surgery (evening of or next morning) when there is adequate hemostasis (Grade 2C). - If using therapeutic-dose SC LMWH and are undergoing high-bleeding-risk surgery, resume therapeutic-dose LMWH 48 to 72 h after surgery (Grade 2C). CHEST 2012; 141(2)(Suppl):e326S e350s

29 DOACs Perioperative Management Looking at Procedure & Creatinine Clearance to decide when to stop DOAC Need to bridge?? When to resume DOAC 18/12/

30 Case 3 KK is a 50 yo man with a PMH of Atrial Fibrillation. CHADS2VASC Score is 1 due to having DM. Anticoagulation regimen: rivaroxaban 20mg po daily Procedure: cardiac catheterization via radial artery Wt=70kg CrCl= 67 ml/min Which of the following represents the best perioperative regimen? a) Give the last dose of rivaroxaban 3 days before surgery and start enoxaparin 70mg SC bid two days before surgery a) Give the last dose of rivaroxaban 3 days before surgery & no need for parenteral anticoagulation a) Give the last dose of rivaroxaban 2 days before surgery & no need to give parenteral anticoagulation b) No need to discontinue rivaroxban 18/12/

31 Appropriate Timing to Withhold DOACs Perioperatively 18/12/2017 European Heart Journal Cardiovascular Pharmacotherapy (2015) 1, doi: /ehjcvp/pvv002 31

32 Appropriate Timing to Withhold DOACs Perioperatively 18/12/2017 Journal of ClinicalAnesthesia(2016) 34,

33 Decision Algorithm: Perioperative Management of DOACs 18/12/2017 Circulation. 2017;135(24). doi: /cir

34 Case 3 KK is a 50 yo man with a PMH of Atrial Fibrillation. CHADS2VASC Score is 1 DM Anticoagulation regimen: rivaroxaban 20mg po daily Procedure: cardiac catheterization via radial artery Wt=70kg CrCl= 67ml/min Which of the following represents the best perioperative regimen? a) Give the last dose of rivaroxaban 3 days before surgery and start start enoxaparin 70mg SC bid two days before surgery b) Give the last dose of rivaroxaban 3 days before surgery & no need for parenteral anticoagulation c) Give the last dose of rivaroxaban 2 days before surgery & no need to give parenteral anticoagulation d) No need to discontinue rivaroxban 18/12/

35 Case 4 KK is a 80 yo man with a PMH of Atrial Fibrillation. CHADS2VASC Score is 7 ( due to his age, history of PAD, DM, HTN, ischemic stroke 6 weeks ago) Anticoagulation regimen: rivaroxaban 20mg po daily Procedure: major orthopedic surgery Wt=70kg CrCl= 67 Which of the following represents the best perioperative regimen? a) Give the last dose of rivaroxaban 3 days before surgery and start start enoxaparin 70mg SC bid two days before surgery b) Give the last dose of rivaroxaban 3 days before surgery & no need for parenteral anticoagulation c) Give the last dose of rivaroxaban 1 day before surgery d) No need to discontinue rivaroxban 18/12/

36 Decision Algorithm: Perioperative Management of NOACs 1. Bleeding risk 2. Thrombotic risk 3. Bleeding versus thrombotic risk 4. Stopping NOAC based on CrCl 5. Decide if parenteral agent is needed for bridge 18/12/2017 Circulation. 2017;135(24). doi: /cir

37 Case 4 KK is a 80 yo man with a PMH of Atrial Fibrillation. CHADS2VASC Score is 7 ( due to his age, history of PAD, DM, HTN, ischemic stroke 6 weeks ago) Anticoagulation regimen: rivaroxaban 20mg po daily Procedure: major orthopedic surgery Wt=70kg CrCl= 67 Platelets: 200,000cells/mm3 TE risk is high and bleeding risk is high But due to recent stroke TE>>>> Which of the following represents the best perioperative regimen? - Give the last dose of rivaroxaban 3 days before surgery and start enoxaparin 70mg SC bid two days before surgery - Give the last dose of rivaroxaban 3 days before surgery & no need for parenteral anticoagulation - Give the last dose of rivaroxaban 1 day before surgery - No need to discontinue rivaroxban 18/12/

38 Bridging Dose Regimens with DOACs is based on provider preference and minimal evidence high-dose regimen (therapeutic-dose ) - enoxaparin 1 mg/kg bid or 1.5 mg/kg daily - tinzaparin 175 International Units/kg daily - IV UFH to reach 1.5 to 2.5 times the control aptt low-dose regimen (prophylactic-dose) - enoxaparin 30 mg bid or 40 mg daily - UFH 5,000-7,500 International Units bid intermediate-dose regimen (between high- and low-dose regimens) - enoxaparin 40 mg bid 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s 38

39 When to stop bridging prior to surgery? - If using therapeutic-dose IV UFH, stop UFH 4 to 6 h before surgery (Grade 2C). - If using therapeutic-dose SC LMWH, administer the last preoperative dose of LMWH approximately 24 h before surgery (Grade 2C). 18/12/2017 CHEST 2012; 141(2)(Suppl):e326S e350s 39

40 Resumption of NOACs Postoperatively 18/12/2017 European Heart Journal Cardiovascular Pharmacotherapy (2015) 1, doi: /ehjcvp/pvv002 40

41 Summary on Periprocedural Management of VKA Steps: 1. Discontinue warfarin allowing for the clearance prior to the operation (INR returns to normal) 1. Warfarin or sintrom- discontinue ~4 days prior to surgery 2. In patients with medium to high risk of thromboembolism, once the anticoagulant is subtherapeutic, begin therapy with a short acting parenteral anticoagulant such as UFH or LMWH Bridging doses: prophylactic or treatment doses 3. Prior to surgery, discontinue the parenteral AC: UFH 6 hours prior to surgery LMWH 24h prior to surgery 4. Resume parenteral anticoagulant after surgery and overlap with warfarin

42 Summary on Perioperative Management of New Oral Anticoagulants 1. Evaluate Procedure Bleeding Risk 2. Evaluate the patient s thromboembolic risk 3. Factors to consider: Specific medication, CrCl & bleeding risk procedure 4. Options considered for perioperative mananagement: 1. Discontinuing the medication with predictable pharmacokinetics and NO BRIDGE or SWITCH to parenteral 2. Some physicians may opt to switch from a NOAC to a parenteral agent ( must follow the package insert guidance) 18/12/2017 BJS 2014; 101: Circulation. 2017;135(24). doi: /cir

43 Any Questions? 18/12/