Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website http://www.gastrores.org

Review

Volume 2, Number 2, April 2009, pages 67-80


Differences in Managing Anticoagulants and Antiplatelets for Gastrointestinal Endoscopy between East and West

Figures

Figure 1.
Figure 1. Recommendations on managing anticoagulants for high-risk patients undergoing high-risk procedures. (a) Warfarin substituted with intravenous heparin infusion. Warfarin should be stopped 3-5 days before the procedure, and be substituted with unfractionized heparin during the cessation period. (b) Warfarin substituted with subcutaneous heparin injection. Subcutaneous low molecular weighted heparin (LMWH) can be used instead of unfractionized heparin. Risk of thromboembolic complications must be carefully weighed against the increased risk of bleeding by maintaining anticoagulation.
Figure 2.
Figure 2. Recommendation on managing antiplatelets for GI endoscopy by risk stratification. For low-risk procedures, GI endoscopy could be performed without discontinuing the antiplatelets. If the patient is Easternist, taking dual therapy with anticoagulants or other antiplatelets, has a history of GI bleeding or ulcer disease, H. pylori infection, or other conditions that increase the risk of bleeding, cessation of drugs should be considered (marked as “Step up” with an arrow in the schema). For high-risk procedures with more than 1% of bleeding complication rate, cessation of antiplatelets should be considered at least 1 week before the procedure, and restarted when there is no evidence of bleeding. If the patient is Westernist, has atrial fibrillation, venous thromboembolism, valvular heart disease, mechanical valve, ischemic heart disease, coronary artery stents, past history of thromboembolism, or other conditions that increase the risk of thromboembolism, shorter cessation of antiplatelets should be considered (marked as “Step down” with an arrow in the schema). The degree of stepping up and down should be decided according to the number and severity of risk factors written above.

Tables

Table 1. Published papers on managing antiplatelets and/or anticoagulants for GI endoscopy (in recent order)
 
Country (author, year)Key Messages
Note: INR, international normalized ratio; LMWH, low molecular weight heparin; EGD, esophagogastroduodenoscopy; ERCP, endoscopic retrograde cholangiopancreaticography; NSAIDs, nonsteroidal anti-inflammatory drugs.
Japan (Fujishiro M, 2009) [8]• Aspirin, ticlopidine, and ethyl icosapentate were stopped 7 days before the procedures by most of the endoscopists, whereas warfarin was stopped 4 days before the procedures.
• With regard to the drug discontinuation before the procedures, no major differences were observed between a biopsy (low-risk procedure) and endoscopic mucosal resection (high-risk procedure).
• In case of higher risk of thromboembolism during the cessation of drugs, most of the endoscopists never performed a biopsy or endoscopic mucosal resection.
Korea (Lee SY, 2008) [1]• Eastern endoscopists do not typically perform an endoscopic biopsy while their patients are on warfarin therapy.
• Eastern endoscopists restarted medications later (1 to 3 days) than Western endoscopists after a biopsy (same day).
• Eastern endoscopists do not perform a polypectomy while their patients are taking aspirin. They withdrew aspirin for more than 7 days before a polypectomy, and restarted it 1 to 3 days after a polypectomy.
UK (Veitch A, 2008) [5]• Low-risk procedures can be performed during warfarin or clopidogrel intake.
• High-risk procedures should be done after stopping warfarin for 5 days (INR < 1.5), and substituted with LMWH in high-risk conditions.
• In low-risk conditions, high-risk procedures can be performed after stopping clopidogrel for 7 days. Aspirin should be considered during the cessation of clopidogrel in such conditions.
• In high-risk conditions, continuing aspirin and stopping clopidogrel for 7 days should be considered, if 12 months have passed drug-eluting coronary stent insertion.
UK (Goel A, 2007) [10]• With regard to warfarin, 26% of the endoscopists stopped for EGD, whereas 48.7% stopped for
colonoscopy.
• During warfarin intake, 21% took biopsies as usual, while 54% performed after checking the INR.
• Warfarin was usually stopped for 3 days. Preferred INR was below 2.0 during the endoscopic procedure.
Israel (Kimchi NA, 2007) [11]• Aspirin can be continued for diagnostic EGD, but should be stopped 5 to 7 days before colonoscopy, spincterotomy, esophageal dilation, endoscopic ultrasound-guided biopsy, or drainage.
• Aspirin use should be avoided for 2 weeks after polypectomy, and 10 days after spincterotomy. However, when the cardiovascular risk is high, aspirin should be resumed within a week after the procedure.
• NSAIDs should be stopped 8 hours before any endoscopy, and be resumed 7 to 14 days after a high-risk procedure.
• Clopidogrel should be stopped 5 days before colonoscopy.
US (Makar GA, 2006) [12]• For low-risk procedure (e.g. diagnostic endoscopy and colonoscopy without polypectomy), there is no need to discontinue or adjust anticoagulation.
• For high-risk procedures (e.g. polypectomy and biliary sphincterotomy), an individual approach is required. This approach includes stopping oral anticoagulant therapy with or without the administration of unfractionated heparin or LMWH during which the patient’s INR is in the subtherapeutic range.
• Antiplatelet therapy can be withheld for high risk procedures, but there is insufficient evidence to indicate that bleeding risk is impacted.
France (Naploen B, 2006) [4]• Low-risk procedures can be performed during medications.
• High-risk procedures and transnasal endoscopy should be performed after the cessation of drugs.
• Colon polypectomy and endoscopic sphincterotomy could be performed without cessation of aspirin or NSAIDs.
Japan (Ogoshi K, 2005) [6]• Warfarin should be stopped 3 to 4 days before all kinds of endoscopic procedure. INR less than 1.5 is preferred during the procedure.
• Aspirin should be stopped 3 days before low-risk procedures, and stopped 7 days before high-risk
procedures.
• Ticlopidine should be stopped 5 days before low-risk procedures, and stop 10 to 14 days before high-risk procedures.
• In case of dual antiplatelet intake (aspirin and ticlopidine), both antiplatelets should be stopped 7 days before low-risk procedures.
Germany (Mosler P, 2004) [13]• Antiplatelets were usually continued before elective procedures including diagnostic EGD, colonoscopy, and ERCP.
• Aspirin and clopidogrel were more frequently stopped than NSAIDs prior to any endoscopic procedure.
• More than 80% stopped aspirin and clopidogrel before elective therapeutic endoscopic procedures.
• Warfarin was usually discontinued 3-5 days prior to the procedure, and was substituted with LMWH.
Belgium (Hittelet A, 2003) [14]• It is not necessary to discontinue aspirin or NSAIDs for endoscopic procedures, when used in standard doses.
• It is not necessary to adjust anticoagulation for low-risk procedures, such as EGD, colonoscopy, ERCP with biopsy or stent insertion (without sphincterotomy).
• For ticlopidine or clopidogrel, it is prudent to discontinue 7 to 10 days for high-risk procedures.
• Warfarin should be discontinued 3 to 5 days before high-risk procedures.
US (Eisen G, 2002) [2]• Any endoscopic procedure may be performed in patients taking aspirin or NSAIDs in the absence of pre-existing bleeding disorders.
• Discontinuation of oral anticoagulation is needed for high-risk endoscopic procedures.
• Consider a heparin window only for patients with high thromboembolic risk.
• Resumption of warfarin is generally recommended at the night of the procedure except for sphincterotomy.
US (Kadakia SC, 1996) [15]• Physicians stopped aspirin and NSAIDs more frequently before colonoscopy and ERCP than before EGD.
• With aspirin or NSAIDs intake, cold biopsy or hot biopsy during EGD or colonoscopy was performed, but sphincterotomy was not.
• Optimal cessation period of aspirin or NSAIDs was less than 10 days.
• Warfarin was resumed immediately after diagnostic endoscopy, whereas 7 days of cessation period was observed after therapeutic endoscopy.

 

Table 2. Reports on embolism that happened during the cessation of antiplatelets and/or anticoagulants
 
Country (author, year)FrequencyType of embolism
EastKorea (Lee SY, 2006) [17]Six of 81 (7.4%) endoscopists have experienced embolism during past one year.5 cerebral infarction
1 mesenteric infarction
Japan (Ishizawa T, 2006) [7]Seven of 81 (8.6%) endoscopists have experienced embolism during past three years.5 cerebral infarction
2 myocardial infarction
Japan (Fujishiro M, 2009) [8]Three of 13 (23.1%) endoscopists have experienced embolism during their career.2 cerebral infarction
1 mesenteric infarction
WestUS (Dunn A, 2003) [21]Twenty nine of 1868 (1.6%) patients undergoing dental or orthopedic procedures, or cataract surgery have experienced thromboembolic events.21 cardiovascular embolism including peripheral arterial thromboembolism
7 cerebral infarction
1 unspecified
US (Garcia D, 2008) [22]Seven of 1024 (0.7%) patients showed embolism during the study period.3 cerebral infarction
2 pulmonary embolism
1 deep vein thrombosis
1 mesenteric infarction
US (Kuwada SK, 1996) [23]One of 27 (3.7%) patients showed embolism during the study period.1 peripheral arterial thromboembolism

 

Table 3. Medications that may potentiate GI bleeding (in alphabetical order)
 
DrugHalf lifeTime of actionMechanism of action
Informations obtained at http://www.rxlist.com, http://kimsonline.co.kr, and http://www.druginfo.co.kr.
Abciximab0.7 hours (in alpha), 10 hours (in beta)0.5-2.5 hoursNonspecific antagonist for glycoprotein IIb/IIIa receptor.
Anagrelide hydrochloride76 hoursLongReduction in platelet production resulting from a decrease in megakaryocyte.
Aspirin0.25-19 hours (depends on dose)0.5-5 hoursIrreversibly acetylates and inactivates cyclooxygenase, and thereby inhibits platelet production of thromboxane A2.
Beraprost sodium1 hour0.5 hourReversibly exacerbates adenylcyclase activation (reversible within 8 hours).
Clopidogrel7-8 hours2 hoursSame with ticlopidine, but has less side effects such as severe neutropenia and thrombotic thrombocytopenic purpura than ticlopidine.
Cilostazol11-13 hours3-6 hoursInhibition of phosphoestrase (reversible within 48 hours).
Dilazep dihydrochloride4 hours0.5-1 hourReversibly inhibits phosphoestrase.
Dipyridamole1.7 hours2-3 hoursReversibly inhibits phosphoestrase and inhibits uptake of adenosine.
Ethyl icosapentate< 24 hoursLongIrreversibly inhibits thromboxane A2 production.
Heparin0.5-2.5 hoursImmediatelyActivates antithrombin III, accerelates the rate of inhibiting clotting enzymes, particulary thrombin and factor Xa.
Ifenprodil tartate1.4 hourShortInhibits binding to serotonin 5HT2 receptor.
Nonsteroidal anti-inflammatory agents< 24 hours0.5 hoursReversibly inhibit platelet cycloxygenase.
Ozagrel sodium1.5 hourShortInhibits enzymatic synthesis of thromboxane.
Sarpogrelate hydrochloride0.7 hour1.5 hourReversibly inhibits binding to serotonin 5HT2 receptor as a selective antagonist.
Ticlopidine12.6 hours6 hoursIrreversibly inhibits the binding of adenosine diphosphate to platelet cell-surface adenosine diphosphate (P2) receptor, and the subsequent ADP-mediated activation of the glycoprotein IIb/IIIa receptor.
Tirofiban1.5-3 hours0.1 hourSpecific antagonist for glycoprotein IIb/IIIa receptor.
Trapidil2-4 hours0.5-2 hoursReversibly inhibits phosphoestrase, reversibly inhibits thromboxane A2 production.
Triflusal0.5 hour24 hoursInhibits platelet arachidonic acid metabolism.
Warfarin36-42 hours72-96 hoursProhibit the synthesis of Vitamin K dependent coagulation factor (II, VII, IX, X) in the liver Vitamin K is used as an antagonist.

 

Table 4. Summary on major differences between the East and West
 
EastWest
Risk of embolismLower than the Westerners.
Common form is cerebrovascular variety that may lead to death or disability.
Higher than the Easterners.
Common form is cardiovascular variety including deep vein thrombosis.
Risk of bleedingHigher than the Westeners due to different drug metabolism (greater body weight-normalized plasma unbound clearance of drug) and higher rate of H. pylori infection.Lower than the Easterners.
Tolerates well with low-risk endoscopic procedures during antiplatelet and/or anticoagulant medications.
Managing warfarinLower international normalized ratio value (1.6-2.6) than the Westerners are appropriate for prophylaxis of thromboembolism.Tolerates well with low-risk procedures (endoscopic biopsy) without significant bleeding.
Managing aspirinLower dose is recommended than the Westerners due to higher risk of bleeding.Tolerates well with few high-risk procedures (endoscopic sphincterotomy and colon polypectomy) without significant bleeding.