Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
BJO Online First, published on April 1, 2014 as 10.1136/bjophthalmol-2014-304902
Review
Managing antiplatelet and anticoagulant drugs in patients undergoing elective ophthalmic surgery Christine A Kiire,1 Rajarshi Mukherjee,1 Neil Ruparelia,2 David Keeling,3 Bernard Prendergast,2 Jonathan H Norris1 1
Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK 2 Department of Cardiology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK 3 Department of Haematology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK Correspondence to Jonathan H Norris, Consultant Ophthalmic Surgeon, Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford OX3 9DU, UK; jonathan. [email protected]
ABSTRACT The management of antiplatelet and anticoagulant treatment can be challenging for the ophthalmic surgeon with the risk of impaired surgical view or potentially sight-threatening haemorrhage. With the advent of newer medications and the expanding usage of these drugs, there is a need for up-to-date guidance on the subject. This paper describes the current use of modern antiplatelet and anticoagulant drugs in the UK, and reviews the evidence of such treatments in the context of ophthalmic surgery. A multidisciplinary approach has been used to develop a guideline for the management of antiplatelet and anticoagulation treatment in elective ophthalmic surgery. Specifically, guidance is provided on when and how to stop antiplatelet and anticoagulant treatment and, importantly, when to seek specialist medical advice.
Received 23 February 2014 Accepted 9 March 2014
INTRODUCTION The ophthalmic surgeon needs to have a working knowledge of the role of antiplatelet (Ap) and anticoagulant (Ac) treatment in patients potentially undergoing surgery. Ap/Ac agents are typically used in the field of stroke prevention in atrial fibrillation (AF), the management of venous thromboembolism (VTE), in patients with mechanical heart valves, in the treatment of acute coronary syndrome (ACS), and in the secondary prevention of cardiovascular disease. Treatment of these conditions is constantly evolving, and a new generation of therapy is now routinely available.1 2 Ap/Ac therapy is known to increase the risk of bleeding, particularly when used in combination. The decision of whether to continue Ap/Ac therapy in ophthalmic surgery, with the inherent risks of potentially sight-threatening complications is complex, particularly as new treatments are developed. This paper attempts to educate the ophthalmologist and the ophthalmic preassessment nurse providing guidance for the optimal management of patients using Ap/Ac therapy.
METHODS To cite: Kiire CA, Mukherjee R, Ruparelia N, et al. Br J Ophthalmol Published Online First: [please include Day Month Year] doi:10.1136/ bjophthalmol-2014-304902
A MEDLINE search was conducted and current UK national guidance3–11 relating to antiplatelet and anticoagulant therapy was reviewed to formulate guidance relating to the safe use of Ac/Ap therapy in ophthalmic surgery. Due to a paucity of good evidence, expert opinion was also sought, including specialists in ophthalmology, cardiology and haematology.
Kiire CA, et al. Br J Article Ophthalmolauthor 2014;0:1–5. doi:10.1136/bjophthalmol-2014-304902 Copyright (or their employer) 2014. Produced
DISCUSSION Antiplatelet and anticoagulant therapy and current clinical use in the UK Antiplatelet drugs Aspirin has been the cornerstone of management for stable coronary artery disease and ACS for 30 years.12 Its action is primarily through the inactivation of platelet cyclo-oxygenase 1 and inhibition of thromboxane production. In combination with aspirin, clopidogrel (an irreversible inhibitor of the platelet P2Y12 receptor) has been the mainstay of secondary prevention of atherothrombotic events in patients with ACS or those following coronary artery stent implantation for the past decade. This regimen has resulted in a significant reduction in cardiovascular events, including mortality. More recently, the development of newer Ap agents which are more potent, have a faster speed of onset, and more predictable effects across all patient groups has been shown to result in a further improvement of outcomes. These agents are now central to contemporary Ap regimens. Prasugrel, like clopidogrel, is of the thienopyridine class. It acts as an ADP receptor antagonist and is a prodrug, with its active form binding irreversibly to the P2Y12 receptor leading to permanent platelet inhibition. Prasugrel is currently approved by the National Institute of Health and Care Excellence (NICE) in the management of certain patients presenting with ST elevation myocardial infarction (STEMI).11 13 Ticagrelor is an oral, reversibly binding P2Y12 antagonist that is rapidly absorbed and reaches peak plasma concentration within 1.5 h of administration. It is approved for the treatment of non-STEMI (NSTEMI) and STEMI patients.14 Other more novel agents, including cangrelor and elinogrel, which are both reversible P2Y12 antagonists, are currently in Phase III clinical trials and may soon reach the clinical setting.
Anticoagulant drugs The oldest Ac drugs currently in use are warfarin (coumadin) and heparin. Warfarin acts by inhibiting production of the vitamin K-dependent clotting factors (II, VII, IX, X) as well as the natural anticoagulant proteins C and S.15 It has been used for decades to treat and prevent VTE. Warfarin is licensed for prophylaxis of systemic embolism in people with rheumatic heart disease and AF, prophylaxis after insertion of prosthetic heart valves, prophylaxis and treatment of VTE and transient attacks of cerebral ischaemia.
by BMJ Publishing Group Ltd under licence.
1
Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
Review Heparin comes in the form of unfractionated heparin (UFH) and, more recently, low molecular weight heparin (LMWH). Both produce their effect by activating antithrombin. Compared with UFH, LMWH has reduced antifactor IIa activity relative to antifactor Xa activity. Heparin has been found to be effective for the prevention and treatment of VTE, for prevention of mural thrombosis after myocardial infarction (MI), and for treatment of patients with unstable angina and MI.16 UFH is usually given intravenously, whereas LMWH is given by subcutaneous injection. Although widely prescribed for thrombotic disorders, warfarin has a number of well documented limitations, including a narrow therapeutic index, the need for regular monitoring, frequent dose adjustment and multiple drug and food interactions.17 Puduserri and colleagues explained how the limitations have led to the development of new classes of direct, small molecule, oral Ac medications.1 They include apixaban, rivaroxaban and dabigatran. Apixaban and rivaroxaban are direct inhibitors of factor Xa. Inhibition of factor Xa prevents thrombin generation and thrombus development. Dabigatran is a direct, reversible inhibitor of thrombin, free and fibrin-bound, and it therefore also inhibits thrombin-induced platelet aggregation. Apixaban is licensed for the prevention of stroke and systemic embolism in adults with non-valvular AF, with one or more of the following risk factors: prior stroke or transient ischaemic attack (TIA), age 75 years or more, hypertension, diabetes mellitus, symptomatic heart failure (New York Heart Association (NYHA) Class II or higher). It is also licensed for VTE in adults who have undergone elective hip or knee replacement surgery. It has NICE approval for these indications.4 Dabigatran is approved by NICE as an option for the prevention of stroke and systemic embolism in adults with non-valvular AF with one or more of the following risk factors: previous stroke, TIA, or systemic embolism; left ventricular ejection fraction less than 40%; symptomatic heart failure, NYHA Class II or higher; age 75 years and older; age 65 years and older with one of the following: diabetes mellitus, coronary artery disease, or hypertension.6 It is also approved by NICE5 and licensed for the primary prevention of VTE in adults who have undergone elective total hip replacement surgery or total knee replacement surgery. Rivaroxaban is approved by NICE as an option for the prevention of stroke and systemic embolism in AF in adults with non-valvular AF with one or more of the following risk factors: congestive heart failure, hypertension, age greater than 75 years, diabetes mellitus, or prior stroke or TIA.8 It also has NICE approval as an option for the prevention of VTE in adults having elective total hip replacement surgery or elective total knee replacement surgery.7 Additionally, it is approved for the treatment of VTE and prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism in adults after diagnosis of acute DVT.9 10 It is licensed for each of these indications.
bruising and haematoma may form due to subcutaneous anaesthesia which is more relevant to oculoplastic surgery.
Intravitreal injections Many patients receiving intravitreal injections of vascular endothelial growth factor inhibitors for conditions such as age-related macular degeneration and diabetic retinopathy are at a higher risk of cardiovascular disease and stroke, independent of the additional risks that are associated with this type of treatment.21 Although these patients may be on Ap/Ac medications, the risk of significant ocular haemorrhage is very small.22
Cataract surgery At present, the most commonly used technique for cataract surgery is phacoemulsification, in which significant complications related to bleeding, even in patients on Ap/Ac drugs, are extremely rare.23 However, in patients with high myopia, glaucoma, diabetes, atherosclerotic vascular disease or hypertension, there may be an increased risk of sight-threatening suprachoroidal haemorrhage.24
Glaucoma surgery Of the wide range of glaucoma surgical procedures, trabeculectomy is the most common.25 Intraoperative or postoperative bleeding complications, including hyphaema, intrableb bleeding and suprachoroidal haemorrhage have been reported which can result in failure of the filtration procedure or loss of sight. The evidence suggests that such complications occur more frequently in patients with Ap/Ac medications.26 Although associated with an increased risk of hyphaema, it may be safe to continue aspirin in patients undergoing trabeculectomy.27 By contrast, patients on warfarin have been found to be at risk of bleeding, increasing the risk of treatment failure.27 Tube implants have also been associated with a risk of hyphaema and suprachoroidal haemorrhage.28
Vitreoretinal surgery The results of published studies relating to bleeding in patients on Ap/Ac drugs undergoing pars plana vitrectomy are conflicting. This applies to diabetic and non-diabetic patients undergoing vitrectomy.29 30 The risk of haemorrhage might be reduced with smaller incision procedures.31
Oculoplastic surgery The procedures involving significant risk of haemorrhage include lacrimal surgery,32 orbital surgery, postseptal eyelid surgery and skin grafts.33 Although there may not be evidence to strongly support or refute a significant increase in haemorrhagic complications in patients on Ap/Ac therapy undergoing oculoplastic procedures, most authors recommend an approach tailored to each patient.34–36
The risk of haemorrhage in ophthalmic surgical procedures There is relatively little evidence relating to the risk of sightthreatening haemorrhagic complications in patients undergoing ophthalmic procedures, particularly in patients using newer Ap/ Ac medications.
Strabismus surgery Although, severe retrobulbar haemorrhage has been reported following squint procedure,37 such incidents are relatively rare.
Local anaesthesia
Corneal surgery
Although rare, the incidence of retrobulbar haemorrhage has been reported with retrobulbar, peribulbar, or sub-Tenon’s anaesthesia,18 and there is no proven increase in incidence in patients with Ap/Ac medications.19 20 It is well recognised that
Suprachoroidal haemorrhage is a rare complication of penetrating keratoplasty38 although it has been reported following endothelial keratoplasty as well.39 There are no studies indicating any increased risk in patients taking Ac/Ap medications.
2
Kiire CA, et al. Br J Ophthalmol 2014;0:1–5. doi:10.1136/bjophthalmol-2014-304902
Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
Review
Box 1 The risk factors of intraoperative and postoperative haemorrhage in ophthalmic surgery40 ▸ ▸ ▸ ▸ ▸
History of bleeding disorders or thromboembolic events Liver failure, renal failure or anaemia41 Cardiac stent Uncontrolled hypertension Herbal treatments like feverfew, garlic, ginger, ginkgo and Asian ginseng42 43 ▸ Family history of bleeding or clotting disorders
A guideline for the management of antiplatelet and anticoagulant drugs in elective ophthalmic surgery Preoperative assessment of patients on antiplatelet and anticoagulant therapy During the preoperative assessment of the patients on Ap/Ac therapy undergoing ophthalmic surgery, attempts should be made to identify the risk factors which could have an impact on surgical success. Box 1 outlines the common risk factors to consider during preoperative assessment. Once the surgery is planned, the decision to stop or continue Ap/Ac therapy is made based on the risks and benefits of each option. Figure 1 provides an illustration of ‘risk stratification’ in this context. The figure is derived from a combination of local and national guidance as well as expert opinion. The type of procedure and the patient-related risk factors are considered
and used to categorise the patient as being at low, medium or high risk of sight-threatening bleeding complications if their Ap/ Ac treatment is continued.
Preoperative antiplatelet treatment If a decision to stop antiplatelet treatment is made, then in patients who do not have a coronary stent it is recommended that their aspirin be stopped 7–10 days preoperatively, to reduce the risk of bleeding. Non-steroidal anti-inflammatory medications which act as reversible platelet inhibitors can be stopped 24–72 h preoperatively. In patients who have a coronary stent, a discussion with the patient’s cardiologist and an agreed management plan is mandatory in advance of surgery. For those in whom a bare-metal coronary stent was placed more than 1 month previously, clopidogrel (or alternative second antiplatelet agent) should be stopped for 7 days prior to the procedure, and aspirin continued throughout the perioperative period. If original stent implantation was undertaken in the context of an ACS, then clopidogrel (or alternative second antiplatelet agent) should be reintroduced once bleeding risk has elapsed. In patients who have undergone drug-eluting coronary stent implantation, dual-antiplatelet therapy should continue for 12 months. In some circumstances, with certain stents, temporary withdrawal of clopidogrel (or alternative second antiplatelet agent) may be feasible at an earlier timepoint following discussion with the patient’s cardiologist. In all cases, the merits of delaying the planned procedure versus performing the procedure with concomitant dual antiplatelet therapy should be considered. Some patients may be on dual antiplatelet therapy for other indications. In these
Figure 1 Ophthalmic surgery risk stratification for bleeding, based on patient comorbidity and Ap/Ac therapy. (UFH, unfractionated heparin; LMWH, low molecular weight heparin; INR, international normalised ratio). Kiire CA, et al. Br J Ophthalmol 2014;0:1–5. doi:10.1136/bjophthalmol-2014-304902
3
Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
Review patients, a management plan should be drawn up in discussion with the patient’s cardiologist/physician.
Table 2 A protocol for stopping dabigatran based on renal function and risk of bleeding during surgery Stop dabigatran before elective surgery
Preoperative anticoagulant treatment Warfarin In patients undergoing elective surgery that requires temporary cessation of treatment, it is recommended that patients stop taking their warfarin 5 days preoperatively, in order that their international normalised ratio (INR) should be near normal at the time of surgery.44–46 Warfarin then needs to be restarted 12–24 h postoperatively, typically the evening after surgery, if haemostasis has successfully been achieved. For patients in whom the risk of thromboembolism is judged high when their INR is dropped below their target therapeutic range (eg, those with mitral metallic heart valves or AF patients with a history of thromboembolic stroke), then bridging with LMWH or UFH is necessary (table 1). If a sight-threatening bleed occurs in a patient on warfarin, then a coagulation screen, a check of renal function and hepatic function should be performed. Reversal of excessive non-major bleeding can be achieved using intravenous vitamin K (typically 5 or 10 mg). Rapid reversal of overanticoagulation for serious bleeding should be with a prothrombin complex concentrate (PCC) or fresh frozen plasma if PCC is not available. To sustain the reversal, intravenous vitamin K should also be infused.
New oral anticoagulants In patients on dabigatran, renal function of the patients needs to be assessed to determine the optimum time to stop it (see table 2). Rivaroxaban should be discontinued at least 24 h before the surgical intervention, and should be restarted as soon as possible after the invasive procedure or surgical intervention. In patients using apixaban, an assessment of the risk of potential surgical bleeding should be made. In moderate to high-risk patients, apixaban should be discontinued at least 48 h prior to surgery. In low-risk patients, this should be stopped at least 24 h prior to surgery. Apixaban should be restarted after the surgery as soon as possible. To reverse the bleeding due to anticoagulation by new oral anticoagulants, surgical intervention is necessary. There may be a role for intravenous tranexamic acid (25 mg/kg), but its usage would need liaising with haematologists.
Renal function (CrCL in mL/min)
Estimated half-life (hrs)
High risk of bleeding/major surgery
Moderate/low risk of bleeding
≥80 ≥50–3 months ago AF with no prior stroke/TIA and without multiple other risk factors Bileaflet aortic MHV with no other risk factors
When bridging with treatment dose heparin should be considered Last episode
BJO Online First, published on April 1, 2014 as 10.1136/bjophthalmol-2014-304902
Review
Managing antiplatelet and anticoagulant drugs in patients undergoing elective ophthalmic surgery Christine A Kiire,1 Rajarshi Mukherjee,1 Neil Ruparelia,2 David Keeling,3 Bernard Prendergast,2 Jonathan H Norris1 1
Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK 2 Department of Cardiology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK 3 Department of Haematology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK Correspondence to Jonathan H Norris, Consultant Ophthalmic Surgeon, Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford OX3 9DU, UK; jonathan. [email protected]
ABSTRACT The management of antiplatelet and anticoagulant treatment can be challenging for the ophthalmic surgeon with the risk of impaired surgical view or potentially sight-threatening haemorrhage. With the advent of newer medications and the expanding usage of these drugs, there is a need for up-to-date guidance on the subject. This paper describes the current use of modern antiplatelet and anticoagulant drugs in the UK, and reviews the evidence of such treatments in the context of ophthalmic surgery. A multidisciplinary approach has been used to develop a guideline for the management of antiplatelet and anticoagulation treatment in elective ophthalmic surgery. Specifically, guidance is provided on when and how to stop antiplatelet and anticoagulant treatment and, importantly, when to seek specialist medical advice.
Received 23 February 2014 Accepted 9 March 2014
INTRODUCTION The ophthalmic surgeon needs to have a working knowledge of the role of antiplatelet (Ap) and anticoagulant (Ac) treatment in patients potentially undergoing surgery. Ap/Ac agents are typically used in the field of stroke prevention in atrial fibrillation (AF), the management of venous thromboembolism (VTE), in patients with mechanical heart valves, in the treatment of acute coronary syndrome (ACS), and in the secondary prevention of cardiovascular disease. Treatment of these conditions is constantly evolving, and a new generation of therapy is now routinely available.1 2 Ap/Ac therapy is known to increase the risk of bleeding, particularly when used in combination. The decision of whether to continue Ap/Ac therapy in ophthalmic surgery, with the inherent risks of potentially sight-threatening complications is complex, particularly as new treatments are developed. This paper attempts to educate the ophthalmologist and the ophthalmic preassessment nurse providing guidance for the optimal management of patients using Ap/Ac therapy.
METHODS To cite: Kiire CA, Mukherjee R, Ruparelia N, et al. Br J Ophthalmol Published Online First: [please include Day Month Year] doi:10.1136/ bjophthalmol-2014-304902
A MEDLINE search was conducted and current UK national guidance3–11 relating to antiplatelet and anticoagulant therapy was reviewed to formulate guidance relating to the safe use of Ac/Ap therapy in ophthalmic surgery. Due to a paucity of good evidence, expert opinion was also sought, including specialists in ophthalmology, cardiology and haematology.
Kiire CA, et al. Br J Article Ophthalmolauthor 2014;0:1–5. doi:10.1136/bjophthalmol-2014-304902 Copyright (or their employer) 2014. Produced
DISCUSSION Antiplatelet and anticoagulant therapy and current clinical use in the UK Antiplatelet drugs Aspirin has been the cornerstone of management for stable coronary artery disease and ACS for 30 years.12 Its action is primarily through the inactivation of platelet cyclo-oxygenase 1 and inhibition of thromboxane production. In combination with aspirin, clopidogrel (an irreversible inhibitor of the platelet P2Y12 receptor) has been the mainstay of secondary prevention of atherothrombotic events in patients with ACS or those following coronary artery stent implantation for the past decade. This regimen has resulted in a significant reduction in cardiovascular events, including mortality. More recently, the development of newer Ap agents which are more potent, have a faster speed of onset, and more predictable effects across all patient groups has been shown to result in a further improvement of outcomes. These agents are now central to contemporary Ap regimens. Prasugrel, like clopidogrel, is of the thienopyridine class. It acts as an ADP receptor antagonist and is a prodrug, with its active form binding irreversibly to the P2Y12 receptor leading to permanent platelet inhibition. Prasugrel is currently approved by the National Institute of Health and Care Excellence (NICE) in the management of certain patients presenting with ST elevation myocardial infarction (STEMI).11 13 Ticagrelor is an oral, reversibly binding P2Y12 antagonist that is rapidly absorbed and reaches peak plasma concentration within 1.5 h of administration. It is approved for the treatment of non-STEMI (NSTEMI) and STEMI patients.14 Other more novel agents, including cangrelor and elinogrel, which are both reversible P2Y12 antagonists, are currently in Phase III clinical trials and may soon reach the clinical setting.
Anticoagulant drugs The oldest Ac drugs currently in use are warfarin (coumadin) and heparin. Warfarin acts by inhibiting production of the vitamin K-dependent clotting factors (II, VII, IX, X) as well as the natural anticoagulant proteins C and S.15 It has been used for decades to treat and prevent VTE. Warfarin is licensed for prophylaxis of systemic embolism in people with rheumatic heart disease and AF, prophylaxis after insertion of prosthetic heart valves, prophylaxis and treatment of VTE and transient attacks of cerebral ischaemia.
by BMJ Publishing Group Ltd under licence.
1
Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
Review Heparin comes in the form of unfractionated heparin (UFH) and, more recently, low molecular weight heparin (LMWH). Both produce their effect by activating antithrombin. Compared with UFH, LMWH has reduced antifactor IIa activity relative to antifactor Xa activity. Heparin has been found to be effective for the prevention and treatment of VTE, for prevention of mural thrombosis after myocardial infarction (MI), and for treatment of patients with unstable angina and MI.16 UFH is usually given intravenously, whereas LMWH is given by subcutaneous injection. Although widely prescribed for thrombotic disorders, warfarin has a number of well documented limitations, including a narrow therapeutic index, the need for regular monitoring, frequent dose adjustment and multiple drug and food interactions.17 Puduserri and colleagues explained how the limitations have led to the development of new classes of direct, small molecule, oral Ac medications.1 They include apixaban, rivaroxaban and dabigatran. Apixaban and rivaroxaban are direct inhibitors of factor Xa. Inhibition of factor Xa prevents thrombin generation and thrombus development. Dabigatran is a direct, reversible inhibitor of thrombin, free and fibrin-bound, and it therefore also inhibits thrombin-induced platelet aggregation. Apixaban is licensed for the prevention of stroke and systemic embolism in adults with non-valvular AF, with one or more of the following risk factors: prior stroke or transient ischaemic attack (TIA), age 75 years or more, hypertension, diabetes mellitus, symptomatic heart failure (New York Heart Association (NYHA) Class II or higher). It is also licensed for VTE in adults who have undergone elective hip or knee replacement surgery. It has NICE approval for these indications.4 Dabigatran is approved by NICE as an option for the prevention of stroke and systemic embolism in adults with non-valvular AF with one or more of the following risk factors: previous stroke, TIA, or systemic embolism; left ventricular ejection fraction less than 40%; symptomatic heart failure, NYHA Class II or higher; age 75 years and older; age 65 years and older with one of the following: diabetes mellitus, coronary artery disease, or hypertension.6 It is also approved by NICE5 and licensed for the primary prevention of VTE in adults who have undergone elective total hip replacement surgery or total knee replacement surgery. Rivaroxaban is approved by NICE as an option for the prevention of stroke and systemic embolism in AF in adults with non-valvular AF with one or more of the following risk factors: congestive heart failure, hypertension, age greater than 75 years, diabetes mellitus, or prior stroke or TIA.8 It also has NICE approval as an option for the prevention of VTE in adults having elective total hip replacement surgery or elective total knee replacement surgery.7 Additionally, it is approved for the treatment of VTE and prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism in adults after diagnosis of acute DVT.9 10 It is licensed for each of these indications.
bruising and haematoma may form due to subcutaneous anaesthesia which is more relevant to oculoplastic surgery.
Intravitreal injections Many patients receiving intravitreal injections of vascular endothelial growth factor inhibitors for conditions such as age-related macular degeneration and diabetic retinopathy are at a higher risk of cardiovascular disease and stroke, independent of the additional risks that are associated with this type of treatment.21 Although these patients may be on Ap/Ac medications, the risk of significant ocular haemorrhage is very small.22
Cataract surgery At present, the most commonly used technique for cataract surgery is phacoemulsification, in which significant complications related to bleeding, even in patients on Ap/Ac drugs, are extremely rare.23 However, in patients with high myopia, glaucoma, diabetes, atherosclerotic vascular disease or hypertension, there may be an increased risk of sight-threatening suprachoroidal haemorrhage.24
Glaucoma surgery Of the wide range of glaucoma surgical procedures, trabeculectomy is the most common.25 Intraoperative or postoperative bleeding complications, including hyphaema, intrableb bleeding and suprachoroidal haemorrhage have been reported which can result in failure of the filtration procedure or loss of sight. The evidence suggests that such complications occur more frequently in patients with Ap/Ac medications.26 Although associated with an increased risk of hyphaema, it may be safe to continue aspirin in patients undergoing trabeculectomy.27 By contrast, patients on warfarin have been found to be at risk of bleeding, increasing the risk of treatment failure.27 Tube implants have also been associated with a risk of hyphaema and suprachoroidal haemorrhage.28
Vitreoretinal surgery The results of published studies relating to bleeding in patients on Ap/Ac drugs undergoing pars plana vitrectomy are conflicting. This applies to diabetic and non-diabetic patients undergoing vitrectomy.29 30 The risk of haemorrhage might be reduced with smaller incision procedures.31
Oculoplastic surgery The procedures involving significant risk of haemorrhage include lacrimal surgery,32 orbital surgery, postseptal eyelid surgery and skin grafts.33 Although there may not be evidence to strongly support or refute a significant increase in haemorrhagic complications in patients on Ap/Ac therapy undergoing oculoplastic procedures, most authors recommend an approach tailored to each patient.34–36
The risk of haemorrhage in ophthalmic surgical procedures There is relatively little evidence relating to the risk of sightthreatening haemorrhagic complications in patients undergoing ophthalmic procedures, particularly in patients using newer Ap/ Ac medications.
Strabismus surgery Although, severe retrobulbar haemorrhage has been reported following squint procedure,37 such incidents are relatively rare.
Local anaesthesia
Corneal surgery
Although rare, the incidence of retrobulbar haemorrhage has been reported with retrobulbar, peribulbar, or sub-Tenon’s anaesthesia,18 and there is no proven increase in incidence in patients with Ap/Ac medications.19 20 It is well recognised that
Suprachoroidal haemorrhage is a rare complication of penetrating keratoplasty38 although it has been reported following endothelial keratoplasty as well.39 There are no studies indicating any increased risk in patients taking Ac/Ap medications.
2
Kiire CA, et al. Br J Ophthalmol 2014;0:1–5. doi:10.1136/bjophthalmol-2014-304902
Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
Review
Box 1 The risk factors of intraoperative and postoperative haemorrhage in ophthalmic surgery40 ▸ ▸ ▸ ▸ ▸
History of bleeding disorders or thromboembolic events Liver failure, renal failure or anaemia41 Cardiac stent Uncontrolled hypertension Herbal treatments like feverfew, garlic, ginger, ginkgo and Asian ginseng42 43 ▸ Family history of bleeding or clotting disorders
A guideline for the management of antiplatelet and anticoagulant drugs in elective ophthalmic surgery Preoperative assessment of patients on antiplatelet and anticoagulant therapy During the preoperative assessment of the patients on Ap/Ac therapy undergoing ophthalmic surgery, attempts should be made to identify the risk factors which could have an impact on surgical success. Box 1 outlines the common risk factors to consider during preoperative assessment. Once the surgery is planned, the decision to stop or continue Ap/Ac therapy is made based on the risks and benefits of each option. Figure 1 provides an illustration of ‘risk stratification’ in this context. The figure is derived from a combination of local and national guidance as well as expert opinion. The type of procedure and the patient-related risk factors are considered
and used to categorise the patient as being at low, medium or high risk of sight-threatening bleeding complications if their Ap/ Ac treatment is continued.
Preoperative antiplatelet treatment If a decision to stop antiplatelet treatment is made, then in patients who do not have a coronary stent it is recommended that their aspirin be stopped 7–10 days preoperatively, to reduce the risk of bleeding. Non-steroidal anti-inflammatory medications which act as reversible platelet inhibitors can be stopped 24–72 h preoperatively. In patients who have a coronary stent, a discussion with the patient’s cardiologist and an agreed management plan is mandatory in advance of surgery. For those in whom a bare-metal coronary stent was placed more than 1 month previously, clopidogrel (or alternative second antiplatelet agent) should be stopped for 7 days prior to the procedure, and aspirin continued throughout the perioperative period. If original stent implantation was undertaken in the context of an ACS, then clopidogrel (or alternative second antiplatelet agent) should be reintroduced once bleeding risk has elapsed. In patients who have undergone drug-eluting coronary stent implantation, dual-antiplatelet therapy should continue for 12 months. In some circumstances, with certain stents, temporary withdrawal of clopidogrel (or alternative second antiplatelet agent) may be feasible at an earlier timepoint following discussion with the patient’s cardiologist. In all cases, the merits of delaying the planned procedure versus performing the procedure with concomitant dual antiplatelet therapy should be considered. Some patients may be on dual antiplatelet therapy for other indications. In these
Figure 1 Ophthalmic surgery risk stratification for bleeding, based on patient comorbidity and Ap/Ac therapy. (UFH, unfractionated heparin; LMWH, low molecular weight heparin; INR, international normalised ratio). Kiire CA, et al. Br J Ophthalmol 2014;0:1–5. doi:10.1136/bjophthalmol-2014-304902
3
Downloaded from bjo.bmj.com on July 10, 2014 - Published by group.bmj.com
Review patients, a management plan should be drawn up in discussion with the patient’s cardiologist/physician.
Table 2 A protocol for stopping dabigatran based on renal function and risk of bleeding during surgery Stop dabigatran before elective surgery
Preoperative anticoagulant treatment Warfarin In patients undergoing elective surgery that requires temporary cessation of treatment, it is recommended that patients stop taking their warfarin 5 days preoperatively, in order that their international normalised ratio (INR) should be near normal at the time of surgery.44–46 Warfarin then needs to be restarted 12–24 h postoperatively, typically the evening after surgery, if haemostasis has successfully been achieved. For patients in whom the risk of thromboembolism is judged high when their INR is dropped below their target therapeutic range (eg, those with mitral metallic heart valves or AF patients with a history of thromboembolic stroke), then bridging with LMWH or UFH is necessary (table 1). If a sight-threatening bleed occurs in a patient on warfarin, then a coagulation screen, a check of renal function and hepatic function should be performed. Reversal of excessive non-major bleeding can be achieved using intravenous vitamin K (typically 5 or 10 mg). Rapid reversal of overanticoagulation for serious bleeding should be with a prothrombin complex concentrate (PCC) or fresh frozen plasma if PCC is not available. To sustain the reversal, intravenous vitamin K should also be infused.
New oral anticoagulants In patients on dabigatran, renal function of the patients needs to be assessed to determine the optimum time to stop it (see table 2). Rivaroxaban should be discontinued at least 24 h before the surgical intervention, and should be restarted as soon as possible after the invasive procedure or surgical intervention. In patients using apixaban, an assessment of the risk of potential surgical bleeding should be made. In moderate to high-risk patients, apixaban should be discontinued at least 48 h prior to surgery. In low-risk patients, this should be stopped at least 24 h prior to surgery. Apixaban should be restarted after the surgery as soon as possible. To reverse the bleeding due to anticoagulation by new oral anticoagulants, surgical intervention is necessary. There may be a role for intravenous tranexamic acid (25 mg/kg), but its usage would need liaising with haematologists.
Renal function (CrCL in mL/min)
Estimated half-life (hrs)
High risk of bleeding/major surgery
Moderate/low risk of bleeding
≥80 ≥50–3 months ago AF with no prior stroke/TIA and without multiple other risk factors Bileaflet aortic MHV with no other risk factors
When bridging with treatment dose heparin should be considered Last episode
