Clopidogrel is an antiplatelet agent that is being increasingly prescribed in both general practice and hospital medicine due to its synergistic action with aspirin, and also for those intolerant of aspirin. The mechanism of action is by irreversibly inhibiting binding of adenosine diphosphate (ADP) to its platelet receptor. This inhibits ADP-mediated activation of glycoprotein IIb/IIIa complex. This in turn inhibits platelet aggregation . As the receptor modification is irreversible, platelet aggregation is impaired for the remainder of the platelets lifespan, generally 7 days. It is because of this permanent effect that the manufacturers, and the current BNF guidelines, recommend stopping clopidogrel 7 days in advance of elective surgery if the antiplatelet effect is not desired . Therefore current practice for the majority reflects the current recommendation.
This recommendation however was based on studies that showed increased rate of post-operative bleeding, need for transfusion, and re-operation rate in patients undergoing cardiothoracic surgery that had clopidogrel continued pre-operatively [6–9]. To our knowledge there has been no research into continued use of clopidogrel peri-operatively in orthopaedic patients.
Patients undergoing orthopaedic surgery have a high incidence of thrombo-embolic complications , especially if no DVT prophylaxis is used . DVT prophylaxis can be both mechanical and pharmacological, and both methods have been shown to decrease thrombo-embolic phenomena in orthopaedic patients [12–14]. Although the new National Institute for Clinical Excellence (NICE) guidelines do not mention it , the Scottish Intercollegiate Guidelines Network (SIGN guidelines) suggests that one method of DVT prophylaxis is aspirin . This was also supported by one of the haematology departments we contacted. It has been shown that aspirin reduces the risk of thrombo-embolic disease, and that the risk of increased postoperative bleeding, haematoma, or infection is low . Therefore we pose the question that although the mechanism of action of both aspirin and clopidogrel is different (aspirin inhibits the cyclo-oxygenase dependent production of thromboxane A2); if aspirin has been shown to be a safe and effective method of DVT prophylaxis in orthopaedic patients could clopidogrel not be used in patients already taking the medication? Currently there appears to be no data available to support this and clopidogrel is not currently licensed for use in DVT prophylaxis.
In our survey 13.9% of respondents did not routinely stop clopidogrel pre-operatively. None of these respondents reported any increased incidence of pre-operative or post-operative complications. This anecdotally seems to suggest that continued use of clopidogrel in patients undergoing orthopaedic surgery may not result in increased risk of complications such as bleeding. This is however contrasted by the reports of increased peri-operative complications (namely bleeding) in those who stop the medication pre-operatively. The finding of increased complications attributable to clopidogrel in those who stop the medication compared with those who do not is paradoxical. There is no literature available to suggest a rebound coagulopathy in patients' that stop clopidogrel pre-operatively. Indeed the likely alternative explanation is that as assessment of bleeding is subjective, consultants who are aware of the complications of clopidogrel may attribute any bleeding to the medication despite having stopped it for a period greater than its' supposed physiologic effect; and those who do not stop the medication may not attribute any increased complications to it. This may be due to a lack of understanding of the mechanism of action of the drug and its effects. There is also the possibility that those who continue clopidogrel are more meticulous with haemostasis due to knowledge of the potential for increased complications. However we are unable to draw any firm conclusions due to the small sample size of our survey.
Our study indicates that there is a lack of uniformity amongst orthopaedic surgeons, and haematologists in Scotland, with regards the need to stop clopidogrel preoperatively. There also appears to be some confusion as to whether additional DVT prophylaxis is needed. Most orthopaedic units did not have a policy to deal with these patients, and the majority did not contact the haematology department at their hospital prior to instituting a policy on stopping clopidogrel. The majority of orthopaedic surgeons also felt that further guidelines in this area would be useful. In order to best manage these patients a multidisciplinary approach is needed to fully assess risk of bleeding compared to risk of an ischemic event when assessing need for anticoagulation.
Our survey raises the following issues. First, is it safe to continue taking clopidogrel in the perioperative period, and if so, is any additional DVT prophylaxis needed or is clopidogrel alone sufficient? Second, in the absence of any current guidelines, are there medico-legal implications if surgeons fail to conform to the British National Formulary advice of stopping clopidogrel 7 days preoperatively? Third, should elective/emergency surgery be delayed until the antiplatelet effect of clopidogrel has worn off?
As this paper was an observational study, there are limitations. Although more than 60% of consultants responded there is the potential for bias as those who responded may have more interest in this subject perhaps due to knowledge of the medication or previous experience of complications. There is also the possibility that those who did not respond do not stop the medication and experienced complications. This would alter the results and therefore the conclusions drawn. However the purpose of this study was to audit the current practice in Scotland and highlight a potential lack of uniformity and the need for further guidance on peri-operative management of these patients.