1. Dr. Hadab A. Mohamed

2. BACKGROUND Temporary interruption Thrombotic risk Continuation Bleeding risk A great challenge, especially in the emergency setting

3. A 55 years old man was noticed to have a progressive loss of vision within 2 weeks. His family took him to the ophthalmology department, where he was discovered to have a huge suprasellar mass and was referred to a neurosurgeon. THE CASE…

4. He had an ST elevation MI 2 years ago and a drug- eluting stent was placed. No further information is available. He also has a history of DVT and PE one month ago following hemicollectomy and has been maintained on warfarin. He is now on aspirin 325 mg, clopidogrel 75 mg, warfarin 4 mg and atenolol 75 mg by mouth daily. CASE WORK-UP BY NEUROSURGEON…

5. The surgeon asked you to assess this man’s coagulation as the patient is worried about visual loss and the surgeon wants to do surgery as soon as possible. THE PERIOPERATIVE DILEMMA

6. WHAT IS YOUR INITIAL ASSESSMENT STRATEGY REGARDING THIS MAN’S COAGULATION? Initial assessment and risk stratification is based on Thrombosis Bleeding Patient Procedure & Interruption Continuation

7. PATIENT RELATED THROMBOTIC RISK? Indication dependent Antithrombotics are indicated for atrial fibrillation, venous thromboembolism and artificial heart valves. The thrombotic risk is defined as the risk of thromboembolism for each condition if not on anticoagulant therapy

8. DVT within the preceding month (As in this patient) During the second and third months of treatment After 3 months of oral anticoagulation High risk of recurrent thromboembolism 40% per year without anticoagulation intermediate risk 10% per year without anticoagulation Low risk Risk of recurrence is about 1.5% per year PATIENT DEPENDENT THROMBOTIC RISK Risk in patients with DVT

9. PATIENT DEPENDENT THROMBOTIC RISK Patients with lone atrial fibrillation and no other risk factors for thromboembolism The lowest risk of stroke (less than 1 per cent per year) Patients with risk factors for stroke Assign one point each for: *Presence of C ongestive heart failure *H ypertension *A ge 75 years or older *D iabetes mellitus *Assign two points for history of S troke or transient ischaemic attack. Risk in patients having atrial fibrillation The stroke rate per 100 patient/year without antithrombotic therapy increases by a factor of 1·5 for each one-point increase in CHADS-2 score. Assessed by CHADS-2 score

10. PATIENT DEPENDENT THROMBOTIC RISK Pts. With artificial heart valves without anticoagulation Incidence of major thromboembolism is approximately 4 per cent per year The thrombotic risk is related to valve site Mitral position produce a greater risk than the aortic position.. The thrombotic risk is increased in those with more than one prosthetic valve Valve design Caged-ball have a greater risk than bi- leaflet valves. Single-leaflet tilting-disc has an intermediate risk. history of thrombosis Greater risk of further thrombosis Risk in patients having artificial heart valves

11. Major surgery Minor surgery 100-fold increase in the absence of thrombolytic therapy Smaller, but definite risk PROCEDURE RELATED THROMBOTIC RISK?

12.  History of congenital or acquired bleeding problems (e.g. liver failure) are associated with high risk of bleeding.  Use of concomitant antiplatelet and NSAIDs increases the chance of perioperative bleeding.  Neurosurgery, vascular surgery and procedures such as renal biopsy are potentially haemorrhagic.  Major surgeries for sure carry an extra risk of bleeding than minor.  Factors such as the location and the accessibility means of controlling bleeding by packing and suturing should be considered. Patient related factorsProcedure related factors WHAT FACTORS SHOULD BE CONSIDERED WHEN ASSESSING INTRAOPERATIVE BLEEDING RISK WITH CONTINUATION OF ANTITHROMBOTIC AGENTS?

13. Our patient is considered at high risk of recurrent thromboembolism with interruption, and at high bleeding risk with continuation of antithrombotic agents. SO, CAN YOU CLASSIFY THIS PATIENT ACCORDING TO THROMBOTIC & BLEEDING RISKS?

14. The patient is now on aspirin 325 mg, clopidogrel 75 mg, warfarin 4 mg and atenolol 75 mg by mouth daily. BACK TO OUR CASE…

15. The risks and benefits of stopping or continuing anticoagulation should be discussed with the patient, and an informed consent should be obtained. BASED ON THE THROMBOTIC AND BLEEDING RISKS, WHAT IS YOUR ADVICE REGARDING WARFARIN? The risk of thrombosis and bleeding should be discussed among the haematologist, surgeon and anaesthetist Low bleeding risk (e.g. dental extractions) may continue warfarin, especially if the INR is within the therapeutic range. If the INR is higher, it should be allowed to return to within range before the procedure. Intermediate bleeding risk (e.g. abdominal surgery) *Further characterization needed, based on their thrombotic risk. *Low thrombotic risk: discontinue warfarin before the procedure. *Intermediate& high thrombotic risk: stop warfarin and substituted with LMWH (Prophylactic dose for the intermediate thrombotic risk group and therapeutic dose for the high-risk group). High risk bleeding (e.g. neurosurgery) as in this case): *Withdraw warfarin and replace with intravenous un- fractionated heparin instead of LMWH * Inferior vena cava filter if there is an additional high thrombotic risk.

16. Most surgical procedures can be performed safely (Insignificant bleeding) when the INR is less than 1.5. For operations with a high bleeding risk (e.g. neurosurgery), the INR should preferably be less than 1.2. If the INR is between 2·0 and 3·0, four scheduled doses of warfarin could be withheld to allow it to fall spontaneously to 1·5 or less before surgery. Extend this period if the initial INR is higher. THEN, WHEN IS IT APPROPRIATE TO WITHDRAW WARFARIN BEFORE SURGERY?

17. So the INR should be checked the day before surgery. If it remains over 2.0, the administration of a low dose of oral vitamin K (1–2 mg) 24 hours before the operation should be considered. WITHDRAWAL OF WARFARIN BEFORE SURGERY…

18. A “bridging Therapy” should be instituted, using heparin, following warfarin withdrawal. Heparin is started, even preoperatively, once the INR is less than 2.0 after cessation of warfarin. THE PRICE TO PAY FOR WARFARIN WITHDRAWAL IS A POTENTIAL RISK OF POSTOPERATIVE THROMBOSIS. HOW DO YOU GUARD AGAINST THAT?

19. The last therapeutic dose of LMWH should be given no less than 12 hours before operation with a twice daily regimen, or 24 hours before operation with a once-daily regimen (Stopping heparin 24 hours before surgery is always acceptable). Intravenous un-fractionated heparin should be stopped 4–6 hours before surgery. SHOULD THE PATIENT BE MAINTAINED ON HEPARIN THROUGHOUT SURGERY?

20. A pragmatic approach would be to start LMWH at a prophylactic dose 12 hours after operation and increase it over 36 hours, especially in patients with high thrombotic risk. If intravenous UFH is chosen, it should be restarted without a loading dose at a rate of no more than 18 units/kg/h. WHAT ARE YOUR RECOMMENDATIONS REGARDING HEPARIN AND WARFARIN POSTOPERATIVELY?

21. Warfarin may be restarted (with the same preoperative maintenance dose) on the evening of surgery or whenever the patient is able to take oral medications. Once warfarin therapy is restarted, it can be expected to take at least 3 days for the INR to reach the usual therapeutic range of 2.0–3.0. POSTOPERATIVE HEPARIN AND WARFARIN...

22. Bridging therapy should be continued until the INR is in the therapeutic range for 2 consecutive days; in the mean time bleeding should be monitored once the anticoagulation has been resumed. Patients receiving either form of heparin should also have regular platelet counts to monitor for heparin-induced thrombocytopenia. POSTOPERATIVE HEPARIN AND WARFARIN...

23. The patient had an ST elevation MI one year ago and a drug-eluting stent was placed. He is now on aspirin 325 mg, clopidogrel 75 mg, warfarin 4 mg and atenolol 75 mg by mouth daily. BACK TO OUR CASE…

24. Premature discontinuation of antiplatelet therapy is the most significant predictor of stent thrombosis, with a mortality rate of 45%. This risk is related to the timing of discontinuation of of antiplatelet. THE PATIENT IS ALSO ON ANTI-PLATELETS, WOULD YOU LIKE TO DISCONTINUE THEM?

25. Discontinuation of clopidogrel during the first month after coronary stent insertion caries a high risk of stent thrombosis during the next year. The same applies to aspirin for a period as long as 15 months after coronary stent insertion WHAT IS THE RISK OF STENT THROMBOSIS WITH ANTI-PLATELETS WITHDRAWAL?

26. In addition, the risk of stent thrombosis increases in patients with renal impairment, diabetes or dehydration. AP WITHDRAWAL……

27. The patient had an ST elevation MI 2 years ago and a drug- eluting stent was placed. No further information is available. He is now on aspirin 325 mg, clopidogrel 75 mg, warfarin 4 mg and atenolol 75 mg by mouth daily. Our patient is at low risk of developing stent thrombosis, but this small risk should be addressed to the patient. ACCORDINGLY, WHAT IS THE RISK OF STENT THROMBOSIS IN THIS PATIENT?

28. The patient has an increased risk of thromboembolism related to both, patient (Recent DVT& PE) and procedure (craniotomy). In addition, our patient is at low risk of developing stent thrombosis. IN SUMMARY…

29. Having a patient with low risk for stent thrombosis the surgeon decided to discontinue AP therapy before surgery for fear of bleeding. What is your advice in this respect?

30. low-dose aspirin ( ˂ 325mg/day) should not be discontinued before an intended operation or procedure unless there is a very high bleeding risk as in intracranial surgery and TURP. However, this might not be reasonable for dual antiplatelet therapy (aspirin and clopidogrel), as in this case, which is known to increase the risk of surgical bleeding. ADVICE….

31. To identify the proper timing of AP discontinuation before surgery a risk-based approach may be considered.  Patients for elective surgery receiving dual antiplatelet therapy should have surgery postponed until the recommended duration of clopidogrel therapy is finished.  If delay is unacceptable, a balance of perioperative risk of stent thrombosis compared with the possibility of increased surgical bleeding related to the procedure is acceptable. ADVICE….

32.  In situations of high bleeding and low risk of stent thrombosis, as in this case, the discontinuation of both clopidogrel and aspirin is logical (at least 7 days before surgery).  In scenarios of high thrombotic and low bleeding risk, dual antiplatelet drug therapy may be continued until the day before surgery if at all possible, otherwise, continuation of at least aspirin should be considered. ADVICE….

33.  With high risk of postoperative bleeding, delay restarting AP until this risk has diminished, and removal of any indwelling catheters has occurred.  Careful monitoring for cardiac ischaemia is imperative in patients who have drugs discontinued because of the high risk of coronary thrombosis.  In the emergency situation, platelet transfusion might be required to correct the thrombopathy induced by AP therapy. WHAT IS YOUR ADVICE TOWARD POSTOPERATIVE RESUMPTION OF AP THERAPY?

34. AN EXTRA MASSAGE FOR THE ANAESTHETIST!!! Prophylactic LMWH Therapeutic LMWH Stop at least 12 h before needle insertion Delay for at least 24 h before needle insertion Removal of epidural catheter Subsequent LMWH dosing 10–12 h after the last dose of LMWH A minimum of 2 h after catheter removal Neuraxial block recommendations in patients receiving anticoagulants& antiplatelets

35. AN EXTRA MASSAGE FOR THE ANAESTHETIST!!! IV UFH Needle placement and catheter removal 4 h after discontinuing heparin Further heparin administration Delay for 1 h after needle placement Neuraxial block recommendations in patients receiving anticoagulants& antiplatelets

36. AN EXTRA MASSAGE FOR THE ANAESTHETIST!!! Aspirin Clopidogrel No added risk of spinal haematoma Stop 7 days preoperatively Emergency surgery Platelet transfusion should be given before the procedure Neuraxial block recommendations in patients receiving anticoagulants& antiplatelets