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E-letters: Electronic letters published:
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Re: Coronary artery stents and non-cardiac surgery.
- Georgina M Howard-Alpe (5 October 2007)
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Re: Perioperative management of antiplatelet therapy
- Georgina M Howard-Alpe (5 October 2007)
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Perioperative management of antiplatelet therapy
- Anuj Bhatia, Harriet Nicholls (14 August 2007)
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Coronary artery stents and non-cardiac surgery.
- C W Kotze, R. Kong , N. Hutchinson, C.M. Harper, S.W. Yusuf (19 July 2007)
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Response to "Regional anaesthesia in patients treated with aspirin and clopidogrel".
- Georgina M Howard-Alpe (11 July 2007)
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Regional anaesthesia in patients treated with aspirin and clopidogrel
- Robert E Self (29 May 2007)
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Response to e-letter "Ticking time bombs in patients hearts
- Georgina M Howard-Alpe (21 May 2007)
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Tiny Ticking Time Bombs in the patients hearts.
- sheshagiri bengeri (11 May 2007)
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Georgina M Howard-Alpe
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Dear Editor We would like to thank Dr Kotze for his interesting and informative letter in response to our article “Coronary artery stents and non-cardiac surgery”.1 Optical light transmission platelet aggregometry, a laboratory based technique, remains the “gold standard” test for the assessment of platelet function and the inhibition in platelet function caused by various antiplatelet agents. It is interesting to observe the significant result discordance between various point of care platelet function tests with regard to the degree of platelet inhibition provided by different antiplatelet agents. Further studies are definitely warranted to identify the most accurate point of care test available. A reliable measure of the inhibition of platelet function would be extremely clinically useful for anaesthetists. However, at present the accuracy of some of these tests is suboptimal. References 1). GM Howard-Alpe, J de Bono, L Hudsmith, WP Orr, JW Sear and P Foex. “Coronary artery stents and non-cardiac surgery”. Brit J Anaesth 2007; 98: 560-74. GM Howard-Alpe Clinical Research Fellow John Radcliffe Hospital Oxford OX3 9DU Conflict of Interest:None declared |
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Georgina M Howard-Alpe
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Dear Editor We would like to thank Dr Bhatia and colleague for their letter in response to our article “Coronary artery stents and non-cardiac surgery”.1 I am delighted and encouraged to hear about the development of local guidelines and an education programme with regard to the perioperative management of patients prescribed clopidogrel in their institution. I hope this example will be repeated in all institutions so that general awareness of the issues and potential dangers involved in the management of these patients will be raised. We would like to stress that, except in cases of "closed space surgery", the evidence is now mounting that dual antiplatelet therapy in patients with coronary artery stents implanted recently should continued throughout the perioperative period.2 In the case of elective closed space surgery, if possible, surgery should be delayed until dual anti- platelet therapy is no longer needed. References 1). GM Howard-Alpe, J de Bono, L Hudsmith, WP Orr, J Sear, and P Foex. “Coronary artery stents and non-cardiac surgery”. Brit J Anaesth 2007; 98: 560-74. 2). P-G Chassot, A Delebays and DR Spahn. “Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction”. Brit J Anaesth 2007; 99: 316-22. Georgina Howard-Alpe Clinical Research Fellow Nuffield Department of Anaesthetics John Radcliffe Hospital Oxford OX3 9DU Conflict of Interest:None declared |
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Anuj Bhatia , Harriet Nicholls
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To the Editor- We read the review article by Howard-Alpe and colleagues on implications of coronary artery stents and antiplatelet therapy in patients undergoing non-cardiac surgery1 with great interest. We agree with the authors’ statements that “the risk of an adverse cardiovascular event if clopidogrel is stopped in the peri-operative period is unknown but is likely to be considerable” and that “there are few data to guide the most appropriate management”. The decision about stopping clopidogrel in the peri-operative period is often made by the surgical team, usually prior to the preoperative anaesthetic evaluation. Lack of adequate information on indications of clopidogrel therapy in a patient and the potential for thrombotic complications following coronary stenting (especially with drug eluting stents) can confound the decision-making process and tilt the risk-benefit balance inappropriately. This has potential implications for patient safety as inappropriate decisions can result in avoidable morbidity and mortality. We recently surveyed 42 consultants from different surgical specialties at our hospital regarding awareness of perioperative implications of dual antiplatelet (clopidogrel and aspirin) therapy in patients with coronary artery stents. The survey included structured questions with categorical and non-categorical answers. The survey forms were sent out in a single internal mailing and the responses were compiled with comments being recorded separately. The majority of consultants (75%) indicated that while they frequently came across patients on low dose aspirin therapy, they only occasionally (<once a month) encountered patients on clopidogrel. There was a lack of consensus about the best strategy for continuing / stopping clopidogrel in the perioperative period and for how long to stop it for. Responses to the question regarding management of antiplatelet therapy in patients with stents who were on both aspirin and clopidogrel while awaiting elective surgery were varied suggesting that awareness about coronary stents (especially the drug eluting variety) and the importance of preventing cardiovascular morbidity through the use of dual antiplatelet therapy could be improved. We were encouraged by comments from majority of respondents indicating that they would consult a cardiologist or anaesthetist for advice. Our survey confirmed that guidelines were required for optimal perioperative management of patients on clopidogrel therapy. As a result we have instituted the following measures: 1. We have drawn up guidelines with the cardiologists regarding peri- operative management of clopidogrel therapy. 2. All patients listed for an operative procedure are screened at the time of listing for clopidogrel use and the notes of all patients on clopidogrel are viewed by a member of the anaesthetic department who regularly anaesthetises for the surgical team due to perform the procedure. Using the local guidelines, the anaesthetist can advise on the peri-operative management of clopidogrel for that patient. 3. If the anaesthetist feels that an individual patient’s case requires discussion between surgeon and cardiologist, they initiate and co-ordinate this process. We believe that this system gives time for an appropriate and safe plan to be formulated for each patient and also prevents unnecessary "on the day" cancellations for patients who should have stopped clopidogrel. This pro- active approach has been well received in our hospital. At the same time we are gradually educating more of our staff on the issues surrounding clopidogrel. A recent editorial has stressed the importance of timing of surgery in relation to percutaneous coronary interventions and the authors advocate careful decisions regarding management of anticoagulation in the perioperative period.2 We feel that greater awareness amongst our surgical and anaesthetic colleagues, consulting our cardiology colleagues as well as clear guidelines would help in optimising perioperative anticoagulant therapy for patients on clopidogrel. Kind regards, Dr Anuj Bhatia, Specialist Registrar Dr Harriet Nicholls, Consultant Luton and Dunstable Hospital, Luton, UK E mail: bhatiaanuj@hotmail.com Declaration from the authors: A modified version of this letter has appeared on the website www.anaesthesiacorrespondence.com (Bhatia A, Nicholls H. Thoracic epidurals and antiplatelet therapy: http://www.anaesthesiacorrespondence.com/Correspond3.asp?articleid=4764&archive=[accessed on 17/03/2007] 1. Howard-Alpe GM, de Bono J, Hudsmith L, Orr WP, Foex P, Sear JW. Coronary artery stents and non-cardiac surgery. Br J Anaesth 2007: 98: 560 -74. 2. Spahn DR, Howell SJ, Delabays A, Chassot PG. Coronary stents and perioperative anti-platelet regimen: dilemma of bleeding and stent thrombosis. Br J Anaesth 2006: 96: 675-7. Conflict of Interest:None declared |
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C W Kotze, Clinical Research Fellow Brighton & Sussex University Hospitals NHS Trust, R. Kong , N. Hutchinson, C.M. Harper, S.W. Yusuf
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Dear Editor We read with interest the following article published in your journal: Coronary artery stents and non-cardiac surgery. Br J Anaesth. 2007 May;98(5):560-74 We found the paper by Howard-Alpe GM et al interesting and helpful. Recently, there has been much emphasis on point of care (POC) platelet function testing, predominantly as a diagnostic aid in measurement of platelet function status, and in monitoring the effect of anti-platelet agents on platelet function (1,2). Currently, several avenues of POC platelet function testing are being explored, of which the majority of the current available options are mentioned in the above study. However we noted that Multiplate® platelet function analysis(Dynabite GmbH, Munich Germany), an increasingly recognised platelet analysis technique(3,4), was not mentioned in the article. Multiplate® platelet function analysis is a whole blood test that is based on impedance aggregometry, which measures electrical impedance between two silver coated copper sensors. As platelets adhere to the sensor wires impedance increases. Multiplate® uses an integrated computer system with five channels which allows for parallel determinations and automatic analysis. Several test reagents are available to allow triggering of different receptors or signal transduction pathways of the platelet, in order to detect its function or response to drugs. Multiplate® differs from Born aggregometry and Single platelet counting in that it takes place on surfaces. Impedance aggregometry revealed a high sensitivity of this method for analysis of aspirin and clopidogrel treated patients(5,6,8). A recent comparison between Multiplate® and a global function analysis using PFA- 100( platelet function analyser) demonstrates Multiplate® provides a more specific test system(3). The use of different activators [ADP(adenosin diphosphate), Prostaglandin E1, Arachidonic Acid, Collagen and TRAP-6 (thrombin receptor activating peptide)] and the possibility to apply different concentrations of the substances, allows varying the sensitivity and specificity of Multiplate® as required. Similarly, Tóth et al found that Multiplate® revealed very convergent results to those obtained by Single platelet counting(4).However, several questions remain unanswered. A recent study that attempted to classify “aspirin non-response” was unsuccessful due to a high degree of discordance between PFA-100 and impedance aggregometry(7). Further clinical studies are needed to show which parameters of platelet function correlate best with useful clinical endpoints. Yours truly, C.W. Kotze Clinical Research Fellow Vascular Surgery Brighton and Sussex University Hospitals NHS Trust References: 1. M.S. Avidan , E.L Alcock , J. Da Fonseca, J. Ponte, JB Desai, G.J. Despotis , B.J. Hunt . Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery. Br J Anaesth. 2004;92:178-86. 2 A.W. Bracey , A.M. Grigore , N.A. Nussmeier. Impact of platelet testing on presurgical screening and implications for cardiac and noncardiac surgical procedures. Am J Cardiol. 2006;98:25N-32N. 3 A. Calatzis, M. Wittwer, B. Krueger. A new approach to platelet function analysis in whole blood-the Multiplate analyser. Platelets 2004;15:479-517 4 O. Tóth, A. Calatzis, S. Penz, H. Losonczy, W. Siess. Multiple electrode aggregometry: A new device to measure platelet aggregation in whole blood. Thromb Haemost 2006;96 5 A. Calatzis, M. Spannagl, F. Theisen. Whole blood aggregation in patients on chronic aspirin and/or clopidogrel treatment. Abstract submitted for the GTH congress February 2007; Society of Thrombosis and Haemostasis Research. 6 G. Bauriedel , D. Skowasch , M. Schneider , R. Andrié , A. Jabs , B. Lüderitz Antiplatelet effects of angiotensin-converting enzyme inhibitors compared with aspirin and clopidogrel: a pilot study with whole-blood aggregometry. Am Heart J. 2003;145:343-8. 7. H.Weisser, K. von Pape M. Dzjan-Horn, A. Calatzis. Control of aspirin effect in cardiovascular patients using two whole blood platelet function assays: PFA-100 and Multiple electrode aggregometry. Clin Chem Lab Med 2006;44:A81-A198 8 S. M. Penz,A. J. Reininger, O. Toth, H. Deckmyn, R. Brandl, W. Siess. Glycoprotein Ibα inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques. Thromb Haemost 2007; 97:435–443 Conflict of Interest:None declared |
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Georgina M Howard-Alpe, Clinical Research Fellow in Anaesthesia
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Editor - I would like to thank Dr Self for his interesting and informative letter. In our review article, “Coronary artery stents and non-cardiac surgery”,2 we highlighted the difficulties and risks associated with performing neuro-axial blockade in patients taking dual antiplatelet therapy with aspirin and clopidogrel. We presented the dilemmas that arise in the care of a patient on dual antiplatelet therapy who needs emergency surgery where neuro-axial blockade is felt to be essential. The question of how many pools of platelets need to be transfused to perform neuro-axial blockade safely was an issue we discussed. We quoted the French guidelines of 2003,4 stating that in the absence of platelet dysfunction, for spinal anaesthesia a platelet count of 50,000 μL-1 should be achieved and for epidural anaesthesia, 80,000 μL-1. Obviously in the case of aspirin and clopidogrel therapy there is platelet dysfunction in the absence of thrombocytopenia. However, at the time we wrote our article the amount of platelet transfusion needed to safely reverse the combined effects of clopidogrel and aspirin therapy was not known. Consequently, we welcome Dr Self’s reference to the recently published healthy volunteers study suggesting at least two to three pools of platelets are needed to normalise platelet function after clopidogrel and aspirin therapy,6 and would advise any clinician to follow this recommendation in the absence of alternative guidelines. With regard to Dr Self’s second point, we would agree that no platelet function test excludes the rare possibility of haematoma following spinal or epidural anaesthesia. Haematoma is a rare complication of neuro-axial blockade that has also been reported in patients not taking either anticoagulant or anti-platelet therapy. In our article we referred to two separate case reports of haematomas following spinal, and combined spinal and epidural anaesthesia; in both cases the clopidogrel was stopped 7 days prior to the procedure.3, 5 As with many aspects of medicine nothing is guaranteed, and patients must be made aware of the possible complications of anaesthesia at consent. Dr Self drew attention to the case report we quoted where platelet aggregometry was used to guide the correction of platelet function with platelet transfusion prior to neuro- axial blockade in the patient undergoing emergency surgery whilst awaiting lung transplantation.1 We believe that in the increasingly litigious world in which we practice medicine, the security of a normal result on platelet function testing or correction of an abnormal result with platelet transfusion, will enable the anaesthetist to feel and prove they did all possible to avoid the devastating complication of epidural haematoma. We agree that the platelet count may well be normal despite abnormal platelet function as can be the case in pre-eclampsia and, as we highlighted, in the patient taking antiplatelet therapy. It is precisely for this reason that we advise if you are to perform neuro-axial blockade on a patient in whom you suspect abnormal platelet function, you should perform platelet function testing and correct the platelet function as guided by the test result or, if testing is unavailable, transfuse platelets before you proceed. Finally, we also agree that platelet transfusion is not without risks to the patient and increasingly platelets are an expensive and scarce resource. Not only, as stated by Dr Self, are there risks of administrative errors, transfusion reactions and infective contamination, but also in this patient subgroup the risk of thrombosis associated with platelet transfusion is high. Subsequently we do not advise neuro-axial blockade in the emergency scenario in patients on dual antiplatelet therapy with aspirin and clopidogrel unless there is an essential indication for the block such as end-stage respiratory disease. In the elective scenario, guidelines state that clopidogrel should be stopped for 7 days before neuro-axial blockade and aspirin can be safely continued. This strategy does not completely rule out the possibility of epidural haematoma but reduces the risk significantly. We believe that communication between members of the clinical team and the patient involved with a full explanation of the risks and benefits of different perioperative strategies is vital as in all situations. Georgina M Howard-Alpe Oxford, UK E-mail: georgina.howard-alpe@nda.ox.ac.uk 1. Herbstreit F, Peters J. “Spinal anaesthesia despite combined clopidogrel and aspirin therapy in a patient awaiting lung transplantation: effects of platelet transfusion on clotting tests”. Anaesthesia 2005; 60: 85-7. 2. Howard-Alpe GM, De Bono J, Hudsmith L, Orr WP, Foex P and Sear J. “Coronary artery stents and non-cardiac surgery”. Br J Anaesth 2007; 98: 560-74. 3. Litz RJ, Gottschlich B, Stehr SN. “Spinal epidural haematoma after spinal anaesthesia in a patient treated with clopidogrel and enoxaparin”. Anesthesiology 2004; 101:1467-70. 4. Samara CM, Djoudi R, Lecompte T, Nathan-Denizot N and Schved JF. “Perioperative platelet transfusion: recommendations of the Agence Francaise de Securite des produits de Sante (AFSSaPS) 2003. Can J Anaesth 2005; 52: 30-7. 5. Tam NL, Pac-Soo C, Pretomas PM. “Epidural haematoma after combined spinal-epidural anaesthetic in a patient treated with clopidogrel and dalteparin”. Br J Anaesth 2006; 96: 262-5. 6. Villahur G, Choi BG, Zafar MU, et al. “Normalisation of platelet reactivity in clopidogrel-treated subjects”. J Thromb Haemost 2007; 5: 82- 90. Conflict of Interest:None declared |
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Robert E Self
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Editor – I read the recent review ‘Coronary artery stents and non- cardiac surgery’ (1) with interest. Dr Howard-Alpe and colleagues refer to the difficult clinical situation in which an anaesthetist wishes to perform a central neuro-axial block on a patient treated with antiplatelet therapy. The authors suggest pre-operative platelet transfusion ‘if regional neuro-axial blockade is thought to be essential’ for emergency surgery. I wish to highlight three practical difficulties in transfusing platelets in order to allow a central neuro-axial block to be performed. Firstly, how many pools of platelets should be transfused? The authors cite French guidelines from 2003, which refer to platelet count (2). However, it is likely that patients taking antiplatelet therapy will have a platelet count of > 100,000 µl-1 and the platelet count tells us little about platelet function. A recent healthy volunteer study suggests that at least two to three pools of platelets may be required to normalise platelet function after clopidogrel and aspirin administration (3). Secondly, how can platelet function be monitored after platelet transfusion to decide that a block may be safely performed? None of the platelet function tests described in the review will exclude the possibility of the very rare complication of haematoma following an epidural or spinal block. The platelet count may be normal despite abnormal platelet function, as demonstrated in pre-eclampsia (4). A case report of spinal anaesthesia in a patient taking clopidogrel and aspirin describes the use of platelet aggregometry to monitor the effect of platelet transfusion (5). However, as Dr Howard-Alpe et al. state, this technique is laboratory based and therefore may be unavailable to the clinician. Finally, is the risk of platelet transfusion prior to central neuro- axial block offset by the perceived benefits of the block to the patient? Platelet transfusion is not without risk including administration errors, and bacterial contamination of platelets (6). Until anaesthetists have further data to support the safety (or otherwise) of epidural and spinal anaesthesia in patients taking both clopidogrel and aspirin, it is likely that those patients in ‘whom regional neuro-axial blockade is thought to be essential’ will be confined to a small group, such as those awaiting lung transplantation (5). R. E. Self London, UK Email: Robert.Self@rmh.nhs.uk References: 1 Howard-Alpe GM, De Bono J, Hudsmith L, Orr WP, Foex P and Sear JW. Coronary artery stents and non-cardiac surgery. Br J Anaesth 2007; 98: 560 -74 2 Samama CM, Djoudi R, Lecompte T, Nathan-Denizot N, Schved JF. Perioperative platelet transfusion: recommendations of the Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSaPS) 2003. Can J Anaesth 2005; 52; 30-7 3 Villahur G, Choi BG, Zafar MU, Viles-Gonzalez JF, Vorchheimer DA, Fuster V, Badimon JJ. Normalisation of platelet reactivity in clopidogrel- treated subjects. J Thromb Haemost 2007; 5; 82-90 4 Davies JR, Fernando R, Hallworth SP. Hemostatic function in healthy pregnant and preeclamptic women: an assessment using the platelet function analyzer (PFA-100®) and thromboelastograph®. Anesth Analg 2007; 104: 416- 20 5 Herbstreit F, Peters J. Spinal anaesthesia despite combined clopidogrel and aspirin therapy in a patient awaiting lung transplantation: effects of platelet transfusion on clotting tests. Anaesthesia 2005; 60: 85-7 6 Serious Hazards of Transfusion - Annual Report 2005. www.shotuk.org Conflict of Interest:None declared |
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Georgina M Howard-Alpe
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Editor-We read with interest the comments of Dr Bengeri, “Ticking time bombs in the patients hearts”, in response to our recent review article on the perioperative management of patients with coronary artery stents undergoing non-cardiac surgery.1 We agree with Dr Bengeri; the patient is indeed the most important person in the equation and it is our desire to ensure the provision of the best information and clinical care to the patient through the education of those involved in their management that led us to write this review article. Our survey in the Oxford region revealed the lack of knowledge and level of confusion that exists about the perioperative management of patients with coronary artery stents undergoing non-cardiac surgery,2 and the lack of formal guidelines only exacerbates this problem. Treatment options should always be discussed with the patient concerned and they should be made aware of the potential risks and benefits of different management strategies. However, we would encourage a universal clear message from all members of the team responsible for the patient’s care and this requires discussion and communication between all involved; anaesthetist, cardiologist, surgeon and haematologist, as recommended in the article. This approach relies on all members of the team being educated and informed about the issues and potential risks involved. We emphasise as stressed in the review, each case must be considered on an individual basis as both the risk and consequences of surgical bleeding and stent thrombosis will vary. Equally, the potential benefits of regional anaesthesia will vary according to the type of surgery and the individual patient’s co-morbidity. As with many issues in medicine it is our job as professionals to weigh up the consequences of the different options available and present information to the patient in a balanced, unbiased manner, advising them of the consensus of medical opinion regarding the safest management plan. This allows the patient to make a truly informed decision. To do this we have a responsibility to gain an excellent understanding of the various risks involved and to be speaking with one voice. Georgina Howard-Alpe Oxford, UK. E-mail: georgina.howard-alpe@nda.ox.ac.uk References: 1). Howard-Alpe GM, De Bono J, Hudsmith L, Orr WP, Sear JW and Foex P. Coronary artery stents and non-cardiac surgery.” Br J Anaesth 2007: 98: 560-74. 2). Hudsmith L, De Bono J, McKenna C, Foex P and Orr WP. Dual Antiplatelet therapy and non-cardiac surgery risk; what are the anaesthetists and surgeons doing? Eur Heart J 2006; 27: 380-1. Conflict of Interest:None declared |
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sheshagiri bengeri, SpR, Anaesthesia, UHW, Cardiff, CF14 4XW
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I read the article by Dr G M Howard -Alpe et al with great interest. The physiology and pharmacology lacked graphical illustration which would have made it more enjoyable. The authors say “their management should involve careful discussion between the surgeons, anaesthetists, cardiologists, and haematologists”. I think we are forgetting the most important person - the patient. We always discuss with the patient before we start any treatment like advantages, disadvantages and complications. We should in my opinion discuss with the patient before stopping any treatment especially before having an operation. Recently I had a patient who was treated with clopidogrel for stroke prevention. Initially she preferred an epidural analgesia for her post operative pain relief. When she realized that she can not have her clopidogrel until the epidural catheter was removed, she chose not to have the epidural. In my opinion if given a choice the patients would prefer to have slightly more blood loss over having another MI or stroke. With the transfusion services so safe now days, I would rather have blood transfusion. The anaesthetists should continue to play the vital role. We should also document patient’s wishes. If we don’t, it might lead to an increase in litigations in the future. Conflict of Interest:None declared |
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