Downloaded from http://bjo.bmj.com/ on November 29, 2014 - Published by group.bmj.com
BJO Online First, published on November 25, 2014 as 10.1136/bjophthalmol-2014-306036 Review
Ophthalmic patients on antithrombotic drugs: a review and guide to perioperative management K-L Kong,1 J Khan2 1
Department of Anaesthesia, SWBH NHS Trust, Birmingham, UK 2 Department of Cardiology, SWBH NHS Trust, Birmingham, UK Correspondence to Dr K-L Kong, Department of Anaesthesia, SWBH NHS Trust, Birmingham B18 7QH, UK; [email protected] Search strategy: MEDLINE and EMBASE electronic databases were searched for papers on anticoagulation and antiplatelet agents in the context of eye surgery. Papers from 1994 to 2014 and their references, in the English language, were included. Received 21 August 2014 Revised 30 October 2014 Accepted 9 November 2014
ABSTRACT The changing profile of patients undergoing ophthalmic surgery, with an increase in prevalence of antiplatelet and anticoagulant drug use, predisposes to bleeding complications. This mandates an awareness of these agents, allowing optimal patient management. We review traditional and newer agents in the context of cataract, vitreoretinal, glaucoma and oculoplastic surgery. Recommendations are given for continuation, cessation and re-commencement of these agents in order to minimise the risk of bleeding and thrombotic/ thromboembolic complications.
INTRODUCTION Patients undergoing eye surgery are increasingly elderly with significant comorbidity. Many are already on anticoagulant or antiplatelet drugs to reduce the risk of thromboembolic and atherothrombotic events, especially in those with atrial fibrillation, recent stroke or myocardial infarction (MI). These drugs may predispose them to the risk of haemorrhagic complications, either during the administration of local anaesthesia or during surgery. This risk must be balanced against that of a thromboembolic event with potentially catastrophic consequences with cessation of antiplatelet or anticoagulant drugs. The aim of this article is to review the evidence and to provide guidance on the perioperative management of ophthalmic patients on antithrombotic drugs.
CATARACT SURGERY AND REGIONAL ANAESTHETIC TECHNIQUES
To cite: Kong K-L, Khan J. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-306036
Several studies have compared bleeding in patients who continued anticoagulant and antiplatelet agents during surgery and those who were either not on these drugs or who stopped them prior to surgery. The local anaesthetic techniques used were peribulbar, retrobulbar or sub-Tenon’s blocks, and the number of patients studied ranged from 255 to 48 862. Aspirin use was widespread with fewer patients taking warfarin and clopidogrel. In a large prospective cohort study of 19 283 cataract operations, Katz and colleagues in 2003 found that the continued use of aspirin and/or warfarin did not increase the risk of ocular haemorrhagic events.1 Kallio and colleagues in 2000 studied 1383 patients on aspirin and/or warfarin scheduled for intraocular surgery requiring peribulbar or retrobulbar anaesthesia.2 They found that the use of these drugs did not predispose to haemorrhagic complications associated with these anaesthetic techniques. A case–control study by Calenda et al in 2012 of 2000 patients undergoing intraocular surgery under peribulbar block found no
difference in ocular haemorrhage grading and potentially sight-threatening local anaesthetic complications between patients taking clopidogrel and those who were not.3 Some studies4–7 have shown an increase in minor haemorrhagic complications such as subconjunctival haemorrhage in patients on warfarin or clopidogrel undergoing sharp needle or sub-Tenon’s anaesthesia. However, there was no increase in potentially sight-threatening local anaesthetic complications (such as retrobulbar or peribulbar haemorrhage) or surgical haemorrhagic complications (such as suprachoroidal haemorrhage and hyphaema). In a systematic review and metaanalysis, patients who underwent cataract surgery while on vitamin K antagonists (VKA) showed an increased risk of bleeding, but almost all haemorrhagic events were self-limited and none of the patients suffered adverse visual outcome because of haemorrhage.8 These results support the continued use of anticoagulants and antiplatelet agents during routine cataract surgery under sharp needle or sub-Tenon’s anaesthesia.
OTHER OCULAR SURGERY Vitreoretinal surgery Although anticoagulant and antiplatelet drugs can be safely continued in many patients having vitreoretinal (VR) surgery, complications have been reported. Two studies, in patients on anticoagulants or antiplatelet agents undergoing VR surgery, each reported a case of subretinal haemorrhage associated with scleral buckling and drainage procedure.9 10 However, subretinal haemorrhage is a known complication of this procedure and may have resulted from trauma to choroidal vessels or acute hypotony. In one study, aspirin had little effect on bleeding but warfarin did increase choroidal haemorrhage or postoperative diabetic vitreous haemorrhage. This led the authors to suggest aspirin be continued during VR surgery but warfarin may be stopped in patients with low thromboembolic risk, each patient’s circumstances being considered individually.11 However, two large studies12 13 concluded that continuation of anticoagulation does not add any significant risk of haemorrhage to the operation, recommending warfarin treatment is continued during vitrectomy surgery. Mason et al14 in 2011 studied 289 patients undergoing 25-gauge vitrectomy surgery. In total, 61 were on warfarin, 118 on clopidogrel and 110 on neither. No patient experienced haemorrhagic complications resulting from peribulbar or retrobulbar blocks. In addition, there was no significant difference in transient vitreous haemorrhage among
Kong K-L, et al. Br J Ophthalmol 2014;0:1–6. doi:10.1136/bjophthalmol-2014-306036
Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://bjo.bmj.com/ on November 29, 2014 - Published by group.bmj.com
Review those on warfarin, clopidogrel or control. Antiplatelet drugs did not increase the risk of postoperative intraocular bleeding.15 In a recent prospective study in 2013, Ryan et al16 assessed the risk of bleeding during VR surgery in patients on anticoagulant and antiplatelet therapy. They found the perioperative bleeding risks in these patients were relatively low and concluded that anticoagulants and antiplatelet agents may be safely continued for the majority of patients undergoing VR surgery. They made the important observation that the single greatest significant independent predictor of intraoperative bleeding was proliferative diabetic retinopathy and of postoperative bleeding was the presence of diabetes mellitus.
Glaucoma surgery Perioperative anticoagulant and a high preoperative intraocular pressure are potential risk factors for haemorrhagic complications in these patients. Cobb and colleagues in 2007 studied the surgical outcome of 367 trabeculectomies, 55 of whom were on aspirin and 5 on warfarin.17 Patients on aspirin had an increased incidence of hyphaema (50.9%) compared with those not on aspirin or warfarin (28%), but this did not affect surgical outcome. However, those on warfarin were found to be at risk of serious haemorrhagic complications compromising surgical success. All five patients on warfarin developed significant hyphaema, two of whom required surgical evacuation. Only one of these patients had long-term success. The authors concluded that it was safe to continue aspirin but recommended careful monitoring of those on warfarin. Patients who experienced haemorrhagic complications either during or after glaucoma surgery had a significantly higher rate of severe loss of vision compared with those who did not experience haemorrhagic complications (17.1% and 5.9%, respectively).18 Patients who continued anticoagulants had the highest rate of haemorrhagic complications (33%) compared with those who discontinued them prior to surgery (15.8%) or those who used antiplatelet agents alone (8.0%). Therefore, anticoagulants and antiplatelet agents, especially warfarin, are associated with haemorrhagic complications. Currently, however, there is no consensus regarding the continuation or discontinuation of these drugs for glaucoma surgery. In a survey of glaucoma surgeons in England in 2008, the majority of them do not stop warfarin or aspirin prior to glaucoma surgery (67% and 69%, respectively).19
Oculoplastic surgery Serious haemorrhagic complications have been associated with oculoplastic procedures. However, their incidence is low. In a retrospective review of 1015 patients undergoing 1130 oculoplastic procedures, Kent and Custer in 2013 found that 39.6% of these patients were on anticoagulants or antiplatelet agents, although many patients failed to disclose their medication usage.20 There was no significant difference in intraoperative or postoperative haemorrhagic complications among those who were not on anticoagulants or antiplatelet agents and those who were on these drugs whether they continued or discontinued prior to surgery. No patient in this study suffered any visual or functional deficit related to bleeding. The authors recommended that anticoagulants and antiplatelet agents may be continued in patients with a history of thromboembolic or cardiovascular disease undergoing procedures associated with little haemorrhagic risk or where the bleeding can be easily addressed. In patients undergoing procedures with a greater haemorrhagic risk such as dacryocystorhinostomy or orbital 2
decompression, the management options should be discussed with both the patient and other clinicians. Currently, most oculoplastic surgeons would prefer to stop antithrombotic agents for these high haemorrhagic risk procedures if it is safe to do so (personal communication).
THROMBOTIC RISKS In the early 1980s, discontinuing anticoagulation was recommended for cataract surgery. However, in a survey of a hundred cataract surgeons who discontinued warfarin before surgery, six patients developed acute strokes, two of whom died.21 In addition, one patient had deep vein thrombosis (DVT) and another had a pulmonary embolus. Thromboembolic complications are often catastrophic. Thrombosis of a mechanical heart valve can be fatal in 15% of patients,22 and embolic stroke can result in major disability or death in 70% of patients.23 24 In a large study of 1293 episodes of warfarin cessation for a range of procedures, most commonly colonoscopy, oral and ophthalmic surgery, in patients with atrial fibrillation, thromboembolism and mechanical heart valves, the risk of thromboembolism was low. Postoperative thromboembolism occurred in 0.7% of cases, none of these had received bridging heparin therapy. Eighty per cent of patients had warfarin therapy withheld for 5 days or fewer. Major bleeding occurred in 0.6%, nonmajor bleeding in 1.7%.25 In general, studies in patients undergoing endoscopy and noncardiac surgery have shown an overall low risk of thromboembolic complications. However, patients with advanced age, severe illness, recurrent venous thromboembolism, thrombophilia, left ventricular dysfunction, sustained atrial fibrillation, a mitral prosthetic valve or >1 prosthetic valve are at higher risk.26–30 Nowadays, fewer cataract surgeons discontinue warfarin preoperatively partly because of an increased awareness of the risks of thromboembolic complications resulting from its discontinuation and also because of advances in cataract surgery. In a 1989 survey of ophthalmologists, 62% of respondents discontinued warfarin preoperatively.31 This figure had fallen to 23.3% in a Canadian Survey in 200332 and just 13.2% by 2009 in a survey of members of the UK Royal College of Ophthalmologists.33 There is substantial evidence that interrupting antiplatelet therapy even for a short duration is associated with an increased risk of serious cardiovascular complications. In a large cohort study, discontinuation of low-dose aspirin resulted in a 40% increase in the risk of stroke, with a longer duration between discontinuation and stroke compared with cardiac events.34 In patients with coronary disease, stopping aspirin or clopidogrel is associated with a twofold to threefold increase in subsequent MI or death.35–37 The relationship between adverse cardiac events and discontinuation of antiplatelet agents is due, in part, to a rebound of platelet reactivity but also to the proinflammatory and prothrombotic effects of surgery.38 39 Premature discontinuation of antiplatelet therapy in patients with drug-eluting stents (DESs) is associated with a marked increase in the risk of late-stent thrombosis (7.8%), a complication associated with an incidence of MI or death of 64%.40
RECOMMENDATIONS FOR PRACTICE Based on current evidence, haemorrhagic complications associated with local anaesthetic blocks (both sharp needle techniques and sub-Tenon’s anaesthesia) are usually minor. Severe sight-threatening haemorrhagic events such as peribulbar and retrobulbar haemorrhage are rare, and the use of anticoagulant Kong K-L, et al. Br J Ophthalmol 2014;0:1–6. doi:10.1136/bjophthalmol-2014-306036
Downloaded from http://bjo.bmj.com/ on November 29, 2014 - Published by group.bmj.com
Review and antiplatelet agents is not associated with an increase in these complications. These agents are also not associated with any increased incidence of haemorrhagic surgical complications during cataract surgery. In contrast, evidence suggests that stopping anticoagulants and antiplatelet agents, particularly in patients with atrial fibrillation, prosthetic heart valves or recent coronary stenting, carries a higher risk of thromboembolic events. Therefore, anticoagulants and antiplatelet agents should be continued during routine cataract surgery. For non-cataract eye surgery, there is less robust evidence to make firm recommendations. Nevertheless, routine VR and oculoplastic surgery appears to be safe in patients on anticoagulants and antiplatelet agents.
Patients on anticoagulants Patients on warfarin should have their international normalised ratio (INR) checked on the day of surgery being within the range that is determined by the condition for which the patient is being anticoagulated. The risk of significant bleeding is relatively low when INR is within the therapeutic range.41 When INR is >3, the incidence of major bleeding is twice as large as when it is between 2 and 3.42 Reducing the warfarin dose preoperatively to bring INR down to the lower limit of the therapeutic range is a safer approach than sudden withdrawal, with consequent hypercoagulability,43 exposing the patient to a risk of thromboembolism. When there are specific haemorrhagic concerns, the decision whether to modify or withhold warfarin therapy is made following an assessment of the patient’s risk for thromboembolic events and the risk for perioperative bleeding to determine how safely antithrombotic therapy can be withheld or whether bridging therapy is needed. The risk of a thromboembolic complication in patients with non-valvular atrial fibrillation is often estimated by means of the CHADS2 score, but more recently the CHA2DS2-VASc score.44 The latter provides better discrimination for assessing risk in the low-to-intermediate risk groups. The greater the cumulative score, the greater the risk of thromboembolic events. Scores of 1 or 2 are allocated based on the presence or absence of the following characteristics: congestive cardiac failure, hypertension, age ≥75, diabetes, prior stroke or transient ischaemic attack (TIA) or thromboembolism, vascular disease, age 65–74 and female sex. Table 1
The aim is to stratify patients into a high-risk, moderate-risk or low-risk group for thromboembolic complications. For patients with venous thromboembolism, the aim is to assess the risk of recurrent embolism during interruption of anticoagulation during the perioperative period. Important considerations are the timing of the most recent thromboembolic event and the presence or absence of prothrombotic risk factors such as thrombophilic disorders or active malignancy (table 1).45 For patients with prosthetic cardiac valves, mitral valves confer higher risk than aortic valves and mechanical valves confer higher risk than tissue valves. These risks must be balanced against the risks of haemorrhage. Factors predisposing patients to haemorrhagic risks include ▸ increasing age ▸ coexisting haematological, vascular, renal or hepatic disease ▸ concurrent medication with steroids or antiplatelet agents ▸ type of proposed procedure, its complexity and anticipated difficulty (table 2).46 Table 3 outlines the approach to perioperative anticoagulation and bridging therapy,47 and figure 1 illustrates the requirement for bridging therapy.45
Inferior vena cava filters It is preferable to defer surgery in patients with a recent thromboembolic event for at least 1 month, but ideally 3 months, for anticoagulant therapy.48 An inferior vena caval (IVC) filter should be considered if surgery is required within 3 months of a proximal DVT or pulmonary embolism.49 Once anticoagulation has been re-established, the IVC filter could be removed depending on the perceived risks.
Newer agents The direct oral anticoagulants (DOA) are a new group of drugs that have recently been introduced into clinical practice. These are direct inhibitors of thrombin such as dabigatran or direct inhibitors of factor Xa such as rivaroxaban. These drugs are expected to replace VKA such as warfarin for the majority of their current indications including the long-term treatment and prevention of venous thromboembolism and the prevention of thromboembolic events in patients with atrial fibrillation. Therefore, we can expect to see an increasing number of patients on DOA presenting for ophthalmic surgery.
Suggested risk stratification for perioperative thromboembolism45
Risk category
Atrial fibrillation
Venous thromboembolism (VTE)
Mechanical heart valve
High (>10%/year arterial thromboembolism risk, or >10%/month venous thromboembolism risk)
CHADS2 score 5–6 CHA2DS2-VASc score 6–9 Recent (
BJO Online First, published on November 25, 2014 as 10.1136/bjophthalmol-2014-306036 Review
Ophthalmic patients on antithrombotic drugs: a review and guide to perioperative management K-L Kong,1 J Khan2 1
Department of Anaesthesia, SWBH NHS Trust, Birmingham, UK 2 Department of Cardiology, SWBH NHS Trust, Birmingham, UK Correspondence to Dr K-L Kong, Department of Anaesthesia, SWBH NHS Trust, Birmingham B18 7QH, UK; [email protected] Search strategy: MEDLINE and EMBASE electronic databases were searched for papers on anticoagulation and antiplatelet agents in the context of eye surgery. Papers from 1994 to 2014 and their references, in the English language, were included. Received 21 August 2014 Revised 30 October 2014 Accepted 9 November 2014
ABSTRACT The changing profile of patients undergoing ophthalmic surgery, with an increase in prevalence of antiplatelet and anticoagulant drug use, predisposes to bleeding complications. This mandates an awareness of these agents, allowing optimal patient management. We review traditional and newer agents in the context of cataract, vitreoretinal, glaucoma and oculoplastic surgery. Recommendations are given for continuation, cessation and re-commencement of these agents in order to minimise the risk of bleeding and thrombotic/ thromboembolic complications.
INTRODUCTION Patients undergoing eye surgery are increasingly elderly with significant comorbidity. Many are already on anticoagulant or antiplatelet drugs to reduce the risk of thromboembolic and atherothrombotic events, especially in those with atrial fibrillation, recent stroke or myocardial infarction (MI). These drugs may predispose them to the risk of haemorrhagic complications, either during the administration of local anaesthesia or during surgery. This risk must be balanced against that of a thromboembolic event with potentially catastrophic consequences with cessation of antiplatelet or anticoagulant drugs. The aim of this article is to review the evidence and to provide guidance on the perioperative management of ophthalmic patients on antithrombotic drugs.
CATARACT SURGERY AND REGIONAL ANAESTHETIC TECHNIQUES
To cite: Kong K-L, Khan J. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-306036
Several studies have compared bleeding in patients who continued anticoagulant and antiplatelet agents during surgery and those who were either not on these drugs or who stopped them prior to surgery. The local anaesthetic techniques used were peribulbar, retrobulbar or sub-Tenon’s blocks, and the number of patients studied ranged from 255 to 48 862. Aspirin use was widespread with fewer patients taking warfarin and clopidogrel. In a large prospective cohort study of 19 283 cataract operations, Katz and colleagues in 2003 found that the continued use of aspirin and/or warfarin did not increase the risk of ocular haemorrhagic events.1 Kallio and colleagues in 2000 studied 1383 patients on aspirin and/or warfarin scheduled for intraocular surgery requiring peribulbar or retrobulbar anaesthesia.2 They found that the use of these drugs did not predispose to haemorrhagic complications associated with these anaesthetic techniques. A case–control study by Calenda et al in 2012 of 2000 patients undergoing intraocular surgery under peribulbar block found no
difference in ocular haemorrhage grading and potentially sight-threatening local anaesthetic complications between patients taking clopidogrel and those who were not.3 Some studies4–7 have shown an increase in minor haemorrhagic complications such as subconjunctival haemorrhage in patients on warfarin or clopidogrel undergoing sharp needle or sub-Tenon’s anaesthesia. However, there was no increase in potentially sight-threatening local anaesthetic complications (such as retrobulbar or peribulbar haemorrhage) or surgical haemorrhagic complications (such as suprachoroidal haemorrhage and hyphaema). In a systematic review and metaanalysis, patients who underwent cataract surgery while on vitamin K antagonists (VKA) showed an increased risk of bleeding, but almost all haemorrhagic events were self-limited and none of the patients suffered adverse visual outcome because of haemorrhage.8 These results support the continued use of anticoagulants and antiplatelet agents during routine cataract surgery under sharp needle or sub-Tenon’s anaesthesia.
OTHER OCULAR SURGERY Vitreoretinal surgery Although anticoagulant and antiplatelet drugs can be safely continued in many patients having vitreoretinal (VR) surgery, complications have been reported. Two studies, in patients on anticoagulants or antiplatelet agents undergoing VR surgery, each reported a case of subretinal haemorrhage associated with scleral buckling and drainage procedure.9 10 However, subretinal haemorrhage is a known complication of this procedure and may have resulted from trauma to choroidal vessels or acute hypotony. In one study, aspirin had little effect on bleeding but warfarin did increase choroidal haemorrhage or postoperative diabetic vitreous haemorrhage. This led the authors to suggest aspirin be continued during VR surgery but warfarin may be stopped in patients with low thromboembolic risk, each patient’s circumstances being considered individually.11 However, two large studies12 13 concluded that continuation of anticoagulation does not add any significant risk of haemorrhage to the operation, recommending warfarin treatment is continued during vitrectomy surgery. Mason et al14 in 2011 studied 289 patients undergoing 25-gauge vitrectomy surgery. In total, 61 were on warfarin, 118 on clopidogrel and 110 on neither. No patient experienced haemorrhagic complications resulting from peribulbar or retrobulbar blocks. In addition, there was no significant difference in transient vitreous haemorrhage among
Kong K-L, et al. Br J Ophthalmol 2014;0:1–6. doi:10.1136/bjophthalmol-2014-306036
Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://bjo.bmj.com/ on November 29, 2014 - Published by group.bmj.com
Review those on warfarin, clopidogrel or control. Antiplatelet drugs did not increase the risk of postoperative intraocular bleeding.15 In a recent prospective study in 2013, Ryan et al16 assessed the risk of bleeding during VR surgery in patients on anticoagulant and antiplatelet therapy. They found the perioperative bleeding risks in these patients were relatively low and concluded that anticoagulants and antiplatelet agents may be safely continued for the majority of patients undergoing VR surgery. They made the important observation that the single greatest significant independent predictor of intraoperative bleeding was proliferative diabetic retinopathy and of postoperative bleeding was the presence of diabetes mellitus.
Glaucoma surgery Perioperative anticoagulant and a high preoperative intraocular pressure are potential risk factors for haemorrhagic complications in these patients. Cobb and colleagues in 2007 studied the surgical outcome of 367 trabeculectomies, 55 of whom were on aspirin and 5 on warfarin.17 Patients on aspirin had an increased incidence of hyphaema (50.9%) compared with those not on aspirin or warfarin (28%), but this did not affect surgical outcome. However, those on warfarin were found to be at risk of serious haemorrhagic complications compromising surgical success. All five patients on warfarin developed significant hyphaema, two of whom required surgical evacuation. Only one of these patients had long-term success. The authors concluded that it was safe to continue aspirin but recommended careful monitoring of those on warfarin. Patients who experienced haemorrhagic complications either during or after glaucoma surgery had a significantly higher rate of severe loss of vision compared with those who did not experience haemorrhagic complications (17.1% and 5.9%, respectively).18 Patients who continued anticoagulants had the highest rate of haemorrhagic complications (33%) compared with those who discontinued them prior to surgery (15.8%) or those who used antiplatelet agents alone (8.0%). Therefore, anticoagulants and antiplatelet agents, especially warfarin, are associated with haemorrhagic complications. Currently, however, there is no consensus regarding the continuation or discontinuation of these drugs for glaucoma surgery. In a survey of glaucoma surgeons in England in 2008, the majority of them do not stop warfarin or aspirin prior to glaucoma surgery (67% and 69%, respectively).19
Oculoplastic surgery Serious haemorrhagic complications have been associated with oculoplastic procedures. However, their incidence is low. In a retrospective review of 1015 patients undergoing 1130 oculoplastic procedures, Kent and Custer in 2013 found that 39.6% of these patients were on anticoagulants or antiplatelet agents, although many patients failed to disclose their medication usage.20 There was no significant difference in intraoperative or postoperative haemorrhagic complications among those who were not on anticoagulants or antiplatelet agents and those who were on these drugs whether they continued or discontinued prior to surgery. No patient in this study suffered any visual or functional deficit related to bleeding. The authors recommended that anticoagulants and antiplatelet agents may be continued in patients with a history of thromboembolic or cardiovascular disease undergoing procedures associated with little haemorrhagic risk or where the bleeding can be easily addressed. In patients undergoing procedures with a greater haemorrhagic risk such as dacryocystorhinostomy or orbital 2
decompression, the management options should be discussed with both the patient and other clinicians. Currently, most oculoplastic surgeons would prefer to stop antithrombotic agents for these high haemorrhagic risk procedures if it is safe to do so (personal communication).
THROMBOTIC RISKS In the early 1980s, discontinuing anticoagulation was recommended for cataract surgery. However, in a survey of a hundred cataract surgeons who discontinued warfarin before surgery, six patients developed acute strokes, two of whom died.21 In addition, one patient had deep vein thrombosis (DVT) and another had a pulmonary embolus. Thromboembolic complications are often catastrophic. Thrombosis of a mechanical heart valve can be fatal in 15% of patients,22 and embolic stroke can result in major disability or death in 70% of patients.23 24 In a large study of 1293 episodes of warfarin cessation for a range of procedures, most commonly colonoscopy, oral and ophthalmic surgery, in patients with atrial fibrillation, thromboembolism and mechanical heart valves, the risk of thromboembolism was low. Postoperative thromboembolism occurred in 0.7% of cases, none of these had received bridging heparin therapy. Eighty per cent of patients had warfarin therapy withheld for 5 days or fewer. Major bleeding occurred in 0.6%, nonmajor bleeding in 1.7%.25 In general, studies in patients undergoing endoscopy and noncardiac surgery have shown an overall low risk of thromboembolic complications. However, patients with advanced age, severe illness, recurrent venous thromboembolism, thrombophilia, left ventricular dysfunction, sustained atrial fibrillation, a mitral prosthetic valve or >1 prosthetic valve are at higher risk.26–30 Nowadays, fewer cataract surgeons discontinue warfarin preoperatively partly because of an increased awareness of the risks of thromboembolic complications resulting from its discontinuation and also because of advances in cataract surgery. In a 1989 survey of ophthalmologists, 62% of respondents discontinued warfarin preoperatively.31 This figure had fallen to 23.3% in a Canadian Survey in 200332 and just 13.2% by 2009 in a survey of members of the UK Royal College of Ophthalmologists.33 There is substantial evidence that interrupting antiplatelet therapy even for a short duration is associated with an increased risk of serious cardiovascular complications. In a large cohort study, discontinuation of low-dose aspirin resulted in a 40% increase in the risk of stroke, with a longer duration between discontinuation and stroke compared with cardiac events.34 In patients with coronary disease, stopping aspirin or clopidogrel is associated with a twofold to threefold increase in subsequent MI or death.35–37 The relationship between adverse cardiac events and discontinuation of antiplatelet agents is due, in part, to a rebound of platelet reactivity but also to the proinflammatory and prothrombotic effects of surgery.38 39 Premature discontinuation of antiplatelet therapy in patients with drug-eluting stents (DESs) is associated with a marked increase in the risk of late-stent thrombosis (7.8%), a complication associated with an incidence of MI or death of 64%.40
RECOMMENDATIONS FOR PRACTICE Based on current evidence, haemorrhagic complications associated with local anaesthetic blocks (both sharp needle techniques and sub-Tenon’s anaesthesia) are usually minor. Severe sight-threatening haemorrhagic events such as peribulbar and retrobulbar haemorrhage are rare, and the use of anticoagulant Kong K-L, et al. Br J Ophthalmol 2014;0:1–6. doi:10.1136/bjophthalmol-2014-306036
Downloaded from http://bjo.bmj.com/ on November 29, 2014 - Published by group.bmj.com
Review and antiplatelet agents is not associated with an increase in these complications. These agents are also not associated with any increased incidence of haemorrhagic surgical complications during cataract surgery. In contrast, evidence suggests that stopping anticoagulants and antiplatelet agents, particularly in patients with atrial fibrillation, prosthetic heart valves or recent coronary stenting, carries a higher risk of thromboembolic events. Therefore, anticoagulants and antiplatelet agents should be continued during routine cataract surgery. For non-cataract eye surgery, there is less robust evidence to make firm recommendations. Nevertheless, routine VR and oculoplastic surgery appears to be safe in patients on anticoagulants and antiplatelet agents.
Patients on anticoagulants Patients on warfarin should have their international normalised ratio (INR) checked on the day of surgery being within the range that is determined by the condition for which the patient is being anticoagulated. The risk of significant bleeding is relatively low when INR is within the therapeutic range.41 When INR is >3, the incidence of major bleeding is twice as large as when it is between 2 and 3.42 Reducing the warfarin dose preoperatively to bring INR down to the lower limit of the therapeutic range is a safer approach than sudden withdrawal, with consequent hypercoagulability,43 exposing the patient to a risk of thromboembolism. When there are specific haemorrhagic concerns, the decision whether to modify or withhold warfarin therapy is made following an assessment of the patient’s risk for thromboembolic events and the risk for perioperative bleeding to determine how safely antithrombotic therapy can be withheld or whether bridging therapy is needed. The risk of a thromboembolic complication in patients with non-valvular atrial fibrillation is often estimated by means of the CHADS2 score, but more recently the CHA2DS2-VASc score.44 The latter provides better discrimination for assessing risk in the low-to-intermediate risk groups. The greater the cumulative score, the greater the risk of thromboembolic events. Scores of 1 or 2 are allocated based on the presence or absence of the following characteristics: congestive cardiac failure, hypertension, age ≥75, diabetes, prior stroke or transient ischaemic attack (TIA) or thromboembolism, vascular disease, age 65–74 and female sex. Table 1
The aim is to stratify patients into a high-risk, moderate-risk or low-risk group for thromboembolic complications. For patients with venous thromboembolism, the aim is to assess the risk of recurrent embolism during interruption of anticoagulation during the perioperative period. Important considerations are the timing of the most recent thromboembolic event and the presence or absence of prothrombotic risk factors such as thrombophilic disorders or active malignancy (table 1).45 For patients with prosthetic cardiac valves, mitral valves confer higher risk than aortic valves and mechanical valves confer higher risk than tissue valves. These risks must be balanced against the risks of haemorrhage. Factors predisposing patients to haemorrhagic risks include ▸ increasing age ▸ coexisting haematological, vascular, renal or hepatic disease ▸ concurrent medication with steroids or antiplatelet agents ▸ type of proposed procedure, its complexity and anticipated difficulty (table 2).46 Table 3 outlines the approach to perioperative anticoagulation and bridging therapy,47 and figure 1 illustrates the requirement for bridging therapy.45
Inferior vena cava filters It is preferable to defer surgery in patients with a recent thromboembolic event for at least 1 month, but ideally 3 months, for anticoagulant therapy.48 An inferior vena caval (IVC) filter should be considered if surgery is required within 3 months of a proximal DVT or pulmonary embolism.49 Once anticoagulation has been re-established, the IVC filter could be removed depending on the perceived risks.
Newer agents The direct oral anticoagulants (DOA) are a new group of drugs that have recently been introduced into clinical practice. These are direct inhibitors of thrombin such as dabigatran or direct inhibitors of factor Xa such as rivaroxaban. These drugs are expected to replace VKA such as warfarin for the majority of their current indications including the long-term treatment and prevention of venous thromboembolism and the prevention of thromboembolic events in patients with atrial fibrillation. Therefore, we can expect to see an increasing number of patients on DOA presenting for ophthalmic surgery.
Suggested risk stratification for perioperative thromboembolism45
Risk category
Atrial fibrillation
Venous thromboembolism (VTE)
Mechanical heart valve
High (>10%/year arterial thromboembolism risk, or >10%/month venous thromboembolism risk)
CHADS2 score 5–6 CHA2DS2-VASc score 6–9 Recent (
