122-001 english

MAY 2002
Volume 1, Issue 1

Antiplatelet agents and
Committee for Continuing
Medical Education

perioperative bleeding
Department of AnesthesiologyUniversity of Montreal Pierre Drolet, MDChairman and Editor Intravascular thrombosis begins with an endothelial lesion, either spontaneous or mechan- ical that exposes the underlying subendothelium, provoking the adhesion of platelets. This adhesion is facilitated by subendothelial glycoproteins such as von Willebrand factor, fibronectin, and collagen. Collagen activates the platelets (resulting in the release of thrombox-ane A and arachidonic acid) and stimulates the release of ADP, serotonin, fibrinogen, and other substances that increase platelet activation. Activated platelets change form, resulting in expo- sure of the glycoprotein (GP IIb/IIIa) receptors. These changes constitute the final common pathway leading to the aggregation of platelets. Ultimately, thrombin activated by the coagula- tion cascade transforms fibrinogen into fibrin, stabilizes the thrombus, but also contributes to the activation of platelets. These steps are schematically shown in Figure 1.
Because this chain of events is so important to the arterial circulation, it is not surprising that the objective of much cardiology research has been focussed on blocking platelet activa- tion and aggregation. There are many drugs, both old and new, that can prevent a thrombus from developing in the coronary and peripheral blood systems. These drugs have different mechanisms of action, variable half-lives, and may or may not be reversed by antagonists. On the other hand, medications such as acetylsalicylic acid (ASA) and nonsteroidal anti-inflamma- tory drugs (NSAIDs) are frequently used for other indications, in particular for rheumatological problems. This usage can pose problems when surgery is necessary, either electively or in anemergency.
This inaugural issue of Anesthesiology Rounds will review the hemorrhagic risk associated University of Montreal
with the currently available antiplatelet agents and present the principles needed to guide the Department of Anesthesiology
evaluation of these risks, based on current research (which is often sparse) from the medical Faculty of Medicine
C.P. 6128, Succursale Centre-VilleMontréal (Québec) H3C 3J7 WHAT ARE ANTIPLATELET AGENTS?
There are mainly 3 types of agents. The mechanisms of action of the available antiplatelet Aspirin and other thromboxane A2 inhibitors
Aspirin (ASA) has been available for more than 100 years and is present in many medica- tions. The advantages of ASA in the field of cardiovascular medicine are well known. It canreduce vascular events by approximately 25%, especially in patients with acute myocardialinfarction (MI) or unstable angina. It is estimated that 32% of patients do not respond to theusual recommended dose and this can have a direct effect on the risk of thrombosis, as well asthe risk of perioperative hemorrhage.
The thienopyridines (ticlopidine and clopidogrel)
Faculty of Medicine
The thienopyridines irreversibly inhibit both platelet aggregation and its amplification Department of Anesthesiology
induced by ADP. When the thienopyridines are used in combination with ASA, there is a syner-gistic effect that further decreases the risk of thrombosis associated with endovascular stents.
Clopidogrel has many advantages when compared to ticlopidine: it has a faster onset of action The editorial content of AnesthesiologyRounds is determined solely by the and fewer of the side-effects (neutropenia and medullar aplasia) that are associated with ticlopi- dine. Ongoing studies suggest that a combination of ASA and a thienopyridine will frequently University of Montreal Faculty of Medicine FIGURE 1 : Steps leading to coronary thrombosis.
after non-cardiac surgery. Reasons for these contradictory Agents are written beside mechanisms of action that they • The variability between studies regarding the length of time that aspirin is withheld before surgery, which may range from a few hours to a few days. With a longer delay, platelet function has more time to return to a normal level that can withstand aggressive surgery • The type of surgery also has an influence on hemor- rhagic risk: tonsillectomy, hip arthroplasty, andtransurethral prostatectomy3 tend to bleed more than Adhesion
surgeries where hemostasis is done meticulously. • Finally, it is clear that susceptibility to ASA varies from one individual to another. Even if the risk of bleed- ing is acceptable or slightly elevated in the majority of surgical patients,4 bleeding risk is severe in a minority of Routine use of ASA (160 mg qd started before the pro- cedure) to prevent thromboembolic events after hip surgery (PEP trial) did not increase perioperative mortality secondary to hemorrhagic complications. However, the authors found an increase in the number of gastrointesti- nal bleeding events, and more importantly, a drop in Amplification
Aggregation and Stabilization
postoperative hemoglobin (average of 2 g/L), as well as an • via TXA and ADP • Platelets aggregate via GP IIb/IIIa increased need for blood transfusions (average of 53 mL).
However, this modest level of hemorrhagic complications tended to occur in patients who were also receiving sub-cutaneous heparin.6 Despite the favourable interpreta- GP IIb/IIIa receptor antagonists
tions of these results, conclusions about the perioperativeuse of aspirin are still debated.7 Inhibition of the GP IIb/IIIa receptors prevents A study conducted by Connelly et al showed that platelet aggregation regardless of the cause. In North hemorrhagic complications were more frequent after hip America, three GP IIb/IIIa inhibitors are available on the arthroplasty in patients taking NSAIDs.8 It is interesting to market. Abciximab (ReoPro®) is the oldest and it produces note that the complications were even more frequent in an almost irreversible inhibition of the GP IIa/IIIb recep- patients using NSAIDs with a half-life of >6 hours (Figure 2). tors. Two more recent products, eptifibatide (Integrelin®) In a series of 1000 orthopedic surgeries performed on and tirofiban (Aggrastat®), produce a comparable inhibi- 924 patients, there were no reports of perimedullar tion of the GP IIb/IIIa receptors. All are rapid-acting with hematoma with either spinal or epidural anesthesia. The short half-lives. Whichever antagonist is used, it must fact that there was no relation between a history of ASA inhibit at least 80% of the receptors to provide clinically use and the presence of blood after insertion of the needle significant inhibition of platelet aggregation. At this time, or catheter led Horlocker et al to conclude that these only intravenous formulations are available, since the agents do not increase the risk of perimedullar hematoma oral formulas gave disappointing results in initial clinical after regional anaesthesia.9 Also, in the PEP trial men- trials. However, in the near future, it is likely that patients tioned earlier,6 there were no cases of perimedullar will be treated with double or triple antiplatelet therapy.1,2 hematoma reported in 4603 surgeries for hip fractures The anesthesiologist must therefore be well aware of the performed under regional anesthesia. Since this complica- associated hemorrhagic risks of therapy and deal with the tion is rare, the statistical power of such studies is debat- able. Nevertheless, interpretations must be extremely cau-tious concerning studies where ASA is mentioned as a ASPIRIN AND NONSTEROIDAL
contributing factor to the appearance of a perimedullar ANTI-INFLAMMATORY DRUGS (NSAIDS)
These drugs comprise the most common antiplatelet Stopping ASA in a patient with coronary disease may drugs that are used and, and as a result, there is abundant increase the risk of a thrombotic event. The life of a research information available on them. However, the platelet is 10 days; platelets start to recover their function- quality of the research varies and precludes any definitive al capacity within 2-3 days after stopping aspirin and are back to normal at 8-10 days. As noted earlier, 80% of theplatelets must be inhibited to cause a significant anti- Non-cardiac surgery
aggregation effect. In healthy subjects, primary hemosta- There are conflicting results in the literature regarding sis is back to normal in 48 hours after stopping aspirin,11 the impact of aspirin on the postoperative risk of bleeding indicating that thrombotic risk appears soon after FIGURE 2 : Perioperative hemorrhagic complications vary
Aprotinine has been clearly shown to be effective in such according to the half-life of the NSAID used. The NSAIDs with a half-life of 0 to 3h are fenoprofen, ibuprofen, THE THIENOPYRIDINES
sodium meclofenamate and tolmetin; with 4 to 5h,indomethacin and ketoprofen; with 6 to 15h, diflunisal, (TICLODIPINE AND CLOPIDOGREL)
naproxen and sulindac; and more than 15h, aspirin and Most of the studies published on these agents have piroxicam. (Reproduced from Connelly et al8) examined their effectiveness in interventional cardiologyand indirectly determined their impact on the associatedhemorrhagic risk. Very few studies have specifically exam- ined the perioperative risks of hemorrhage related to theuse of thienopyridines.
Non-cardiac surgery
Hemorrhagic risks and thromboembolic complica- tions were studied in patients undergoing transabdominal prostatectomy21 or aorto-bifemoral bypass.22 In both groups, ticlodipine was started 2 to 5 days preoperatively.
In both cases, the increase in bleeding and the need for transfusion was approximately 25%, not statistically sig- nificant given the large spread of the results. On the otherhand, ticlopidine prolonged platelet survival (known tobe diminished in the presence of a vascular graft) and stopping ASA treatment.12 In vascular surgery patients, diminished the number of platelets adhering to the Samama et al demonstrated that hemostasis is activated graft.22 In both studies, ticlopidine was started a short in the immediate postoperative period, indicating an time before surgery, suggesting that hemorrhagic risk was increase in thrombotic risk.13 In another study, continu- underestimated and that its antiplatelet activity did not ing aspirin in patients undergoing infrainguinal vascular have sufficient time to reach its full impact. Given that surgery appeared to decrease perioperative mortality and ticlopidine has a long half-life, Desager recommends that prolong life, which questions the systematic withdrawal ticlopidine be stopped 2 weeks prior to any surgery, Nonetheless, it is difficult to make universal recom- Clopidogrel, like aspirin, has a cumulative effect on mendations regarding the use of antiplatelet agents in the platelet aggregation that requires 7 to 9 days to recover.
perioperative period. An expert panel of the Société Based on this theory, it appears reasonable to stop Française d’Anesthésie et de Réanimation concluded that: thienopyridines at least 1 week (commonly 10 days) “In patients presenting with either coronary or cere- before an elective procedure to allow platelet function to brovascular pathology, long-term treatment with aspirin return to normal. The risk of a rebound thrombotic acci- is recommended and should not be stopped in the periop- dent is comparable to that of stopping aspirin, and this erative period unless the risk of hemorrhagic complica- risk suggests restarting the drug early in the postopera- tions related to a specific procedure appears to be greater than the increase in the cardiovascular (thrombotic) risk The incidence of thrombotic complications and/or (especially of an acute coronary syndrome) from with- hemorrhages in patients operated on soon after deploy- ment of a coronary endovascular stent is prohibitive.23These patients must receive antiplatelet therapy consist- Cardiac surgery
ing of combination of aspirin and ticlopidine for at least As is the case for all surgeries, the importance of 2 to 4 weeks after angioplasty. Stopping antiplatelet med- hemorrhagic risk associated with NSAIDs, and ASA in ication considerably increases the risk of a coronary particular, remains controversial in cardiac surgery. Con- thrombosis, but continuing it is associated with an flicting results are abundant in the literature.16,17,18 In an increased risk of both hemorrhage and the need for blood extensive review of 50 articles covering more than 10,000 transfusions.23 As a result, elective surgery should be patients under-going operations in 70 hospitals, Bélisle avoided for a period of 1 to 3 months following place- and Hardy concluded that bleeding was only increased ment of a stent.15 On the other hand, if coronary angio- by 300 mL in most of the studies. This modest increase in plasty is necessary before emergency surgery, the deploy- bleeding does not explain the great variation in transfu- ment of a stent should be avoided. Finally, the safety of sion rates from one hospital to another.4 In practical regional anesthesia in a patient on thienopyridines has terms, since it appears impossible to predict the hemor- not been established or specifically studied as yet.
rhagic risk in a given patient, it seems reasonable to wait Cardiac surgery
until the patient is taken off extracorporeal circulation,heparin is neutralized, and surgical hemostasis is com- Few studies have been published on the relationship pleted before transfusing exogenous platelets, as needed.
between the thienopyridines and the perioperative risk of hemorrhage for surgeries performed under extracor- • EPILOG (Evaluation of PTCA to Improve Long- poreal circulation. Theoretically, considering the pro- term Outcome by c3E7 GP IIb/IIIa receptor block- longed half-life of these drugs, one might expect an increase in the risk of hemorrhagic events. This • EPISTENT (Evaluation of Platelet IIb/IIIa increased risk has been described in at least 2 stud- ies.24,25 On the other hand, the use of thienopyridines During the course of these studies, some patients in the perioperative period appears to decrease needed to have an emergency myocardial revascular- thrombosis associated with valvular prostheses.26 ization. In the EPIC study, the need for transfusions The anti-aggregating effect of ticlopidine in the peri- in patients treated with abciximab who were operat- operative period could also contribute to fewer ed on was the same as in those treated with placebo.
thrombotic events related to the oxygenator, with- However, it should be noted that in the majority of out increasing the risk of hemorrhage or transfu- cases, the drug was stopped more than 24 hours sion.27 These results are from studies done in the before surgery.29 The combined results for patients early 80s, and although interesting, have not been operated on in both the EPILOG and EPISTENT stud- ies are essentially the same, except for an increased Finally, the efficacy of aprotinine in limiting the need for platelet transfusions.30 Once again, most of bleeding associated with thienopyridines remains the patients were taken to the operating room >12 A study by Gammie et al demonstrated a marked GP IIB/IIIA RECEPTOR ANTAGONISTS
increase in the hemorrhagic risk and in the transfu- Non-cardiac surgery
sion needs of patients operated on <12 hours follow- There is no literature regarding the specific hem- ing the interruption of abciximab.31 For emergency orrhagic risk related to aggregation inhibition by the surgeries, prophylactic transfusions of platelets GP IIb/IIIa receptor antagonists in the perioperative reduce both postoperative bleeding and the need for period. The observations and recommendations that transfusions of red blood cells (RBCs) and fresh plas- have been drawn from cardiac surgery may then be ma, bringing them to a level similar to the one extended to non-cardiac surgery. A review of the reported in other populations presenting the same literature on the hemorrhagic risks associated with risk factors.32 Since any unbound medication in the anti-GP IIb/IIIa allows a presentation of general prin- serum disappears rapidly after stopping the perfu- ciples, regarding, for example, the delay between sion, the abciximab that remains bonds equally to stopping the antiplatelet drug and the start of native and exogenous platelets. This directly dimin- ishes the occupancy rate of the receptors, so that As a general rule, there must be a balance between the hemorrhagic risk and the significant risk Recently, Steinhubl et al demonstrated that there of coronary thrombosis, especially if a transfusion of was great inter-individual variability in the function- platelets becomes necessary. Finally, it is important al recovery of platelets after stopping a GP IIb/IIIa to remember that most patients receiving GP IIb/IIIa receptor inhibitor perfusion; this recovery was often receptor inhibitors are also receiving aspirin and are faster than expected.33 Systematic transfusion of platelets is therefore not recommended, but shouldbe assessed by considering hemostasis after neutral- Cardiac surgery
ization of heparin with protamine.29 It is important The oldest GP IIb/IIIa receptor antagonist, and to remember that abciximab is eliminated by certainly the one most clinicians are familiar with, is hemofiltration during extracorporeal circulation. A abciximab. Although, as mentioned earlier, this drug summary of the recommendations regarding abcix- produces an almost irreversible antiplatelet effect,1 it imab in patients undergoing cardiac surgery is pre- has been shown that 12 hours after stopping an IV sented in Table 1. It is imperative to note that perfusion, the relative occupancy of GP IIb/IIIa platelet transfusions before surgery are not recom- receptors drops to around 68%.28 Given the fact that mended, and may even be detrimental. When nor- 80% of the receptors need to be inhibited to have a malizing platelet function there is a risk of accelerat- significant clinical impact, this produces a normal- ing the thrombotic process which is the the reason ization of the bleeding time, (the usual test used to why the patient is receiving a GP IIb/IIIa antagonist.
evaluate the efficacy of the treatment). For the other GP IIb/IIIa receptor inhibitors, sur- Three major multicentre studies have evaluated gical experience is limited. However, since the half- the efficacy of abciximab in decreasing thrombotic life is shorter and the inhibitory effect is competitive complications after coronary angioplasty: in nature, hemorrhagic risks are probably less impor- • EPIC (Evaluation of c7E3 to Prevent Ischemic tant. Recently, we encountered a patient being treat- ed with tirofiban who needed an emergency myocar- TABLE 1: Emergency coronary surgery: General
1. Steinhubl SR. Antiplatelet agents in cardiology: the choice recommendations for patients taking abciximab29,34 of therapy. Ann Thorac Surg 2000;70(2 Suppl):S3-8.
2. King SB, 3rd. Optimizing antiplatelet therapy in coronary 1. When possible, respect a 12-hour delay between interventions. Clin Cardiol 2000;23 Suppl 6:VI-8-13.
stopping the perfusion and performing the surgery, 3. Thurston AV, Briant SL. Aspirin and post-prostatectomy • evaluate the risk of postponing the surgery haemorrhage. Br J Urol 1993;71(5):574-6.
4. Belisle S, Hardy JF. Hemorrhage and the use of blood prod- • evaluate the risk of postponing the surgery ucts after adult cardiac operations: myths and realities.
Annals of Thoracic Surgery 1996;62(6):1908-17.
vs risks related to other morbidity factors 5. Ferraris VA, Ferraris SP. Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass • remember that abciximab prolongs ACT from grafting. Updated in 1995. Annals of Thoracic Surgery 1995;59:1036-1037.
6. Prevention of pulmonary embolism and deep vein throm- 3. Use hemoconcentration during ECC to help bosis with low dose aspirin: Pulmonary Embolism Preven- tion (PEP) trial. Lancet 2000;355(9212):1295-302.
7. Cohen A, Quinlan D. PEP trial. Pulmonary Embolism Pre- 4. Transfuse platelets as needed, after assessing vention. Lancet 2000;356(9225):247; discussion 250-1.
bleeding once heparin has been neutralized 8. Connelly CS, Panush RS. Should nonsteroidal anti-inflam- matory drugs be stopped before elective surgery? Arch 5. Assure optimal mediastinal drainage to decrease Intern Med 1991;151(10):1963-6.
9. Horlocker TT, Wedel DJ, Schroeder DR, Rose SH, Elliott BA, McGregor DG, et al. Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated withregional anesthesia. Anesth Analg 1995;80(2):303-9.
ACT = activated coagulation timeECC = extracorporeal circulation 10. Pryle BJ, Carter JA, Cadoux-Hudson T. Delayed paraplegia following spinal anaesthesia. Spinal subdural haematomafollowing dural puncture with a 25 G pencil point needleat T12-L1 in a patient taking aspirin. Anaesthesia 1996; dial revascularization; the tirofiban perfusion was stopped just before the surgery. This patient did not 11. Sonksen JR, Kong KL, Holder R. Magnitude and time course of impaired primary haemostasis after stopping experience any excessive perioperative bleeding. In chronic low and medium dose aspirin in healthy volun- fact, some have suggested that the use of GP IIb/IIIa teers. Br J Anaesth 1999;82(3):360-5.
receptor antagonists might produce a “platelet anes- 12. Collet J, Montalescot G. Interruption des antithrombo- tiques chez le coronarien. Conséquences et attitudes pra- thesia,” contributing protective benefits during tiques. Cardinale 1998;X(10):12-14.
extracorporeal circulation. Although this theory is 13. Samama CM, Thiry D, Elalamy I, Diaby M, Guillosson JJ, logical and appealing, it is still only a working Kieffer E, et al. Perioperative activation of hemostasis in hypothesis. Further research to evaluate its potential vascular surgery patients. Anesthesiology 2001;94(1):74-8.
14. Neilipovitz DT, Bryson GL, Nichol G. The effect of periop- benefits will be possible only when we have at our erative aspirin therapy in peripheral vascular surgery: a decision analysis. Anesth Analg 2001;93(3):573-80.
15. Société Française d’Anesthésie et de Réanimation, Groupe CONCLUSION
d’étude sur l’hémostase et la thrombose de la SociétéFrançaise d’Hématologie. Agents antiplaquettaires et péri- Antiplatelet agents are being used more and more ode périopératoire. In: Société Française d’Anesthésie et de often in modern medical practice, either for their Réanimation, editor. Conférence d’experts; 2001.
16. Reich DL, Patel GC, Vela-Cantos F, Bodian C, Lansman S.
anti-inflammatory effects or for controlling platelet Aspirin does not increase homologous blood requirements function itself. It is likely that in the near future, coro- in elective coronary bypass surgery. Anesth Analg 1994;79 nary patients will be prescribed 2 or 3 antiplatelet 17. Tuman KJ, McCarthy RJ, O’Connor CJ, McCarthy WE, agents on a long-term basis. For elective surgery, it Ivankovich AD. Aspirin does not increase allogeneic blood will be possible to replace long acting molecules by transfusion in reoperative coronary artery surgery. Anesth medications with a short half-life. This will allow the controlled interruption of antiplatelet therapy in the 18. Kallis P, Tooze JA, Talbot S, Cowans D, Bevan DH, Treasure T. Pre-operative aspirin decreases platelet aggregation and immediate perioperative period and to restart it as increases post- operative blood loss—a prospective, ran- soon as the hemorrhagic risk appears reasonable.
domised, placebo controlled, double-blind clinical trial in100 patients with chronic stable angina. Eur J Cardiothorac In the context of emergency surgery, prolonging the delay between the withdrawal of the antiplatelet 19. Ivert T, Intonti M, Stain-Malmgren R, Dumitrescu A, Blom- agent(s) and the performance of surgery will often back M. Effects of aprotinin during cardiopulmonary permit a decrease in the risk of bleeding. Adjunctive bypass in patients treated with acetylsalicylic acid. ScandCardiovasc J 1998;32(5):289-95.
therapy such as aprotinine may also be useful, as is 20. Bidstrup BP, Hunt BJ, Sheikh S, Parratt RN, Bidstrup JM, the judicious use of platelet transfusions to allow the Sapsford RN. Amelioration of the bleeding tendency of pre- normalization of platelet function. However, as with operative aspirin after aortocoronary bypass grafting. AnnThorac Surg 2000;69(2):541-7.
all other transfusion situations, the prophylactic use 21. Brommer EJ. The effect of Ticlopidine upon platelet func- of platelet transfusions is not recommended, rather, tion, haemorrhage and post- operative thrombosis in transfusions should be given only as needed to cor- patients undergoing suprapubic prostatectomy. J Int Med Res1981;9(3): 203-10.
rect clinically significant hemostatic abnormalities. 22. Nevelsteen A, Mortelmans L, Van de Cruys A, Merckx E, Ver- Methods: Responses to questions formulated by the Organiz-
haeghe R. Effect of ticlopidine on blood loss, platelet turnover ing Committee were drafted by a group of experts and and platelet deposition on prosthetic surfaces in patients under- reviewed by a multidisciplinary Reading Committee. Recom- going aorto-femoral bypass grafting. Thromb Res 1991;64(3): mendations were classified (grade) according to the evidence level of the studies supporting them.
23. Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastroph- ic outcomes of noncardiac surgery soon after coronary stenting.
Principal findings: First, antiplatelet agents have a variable
J Am Coll Cardiol 2000;35(5):1288-94.
effect on hemostasis as far as bleeding risk is concerned.
24. Mössinger H, Dietrich W, Richter J. Antiplatelet therapy with Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) ticlopidine increases blood loss and transfusion in coronary increase intra- and postoperative bleeding moderately, but not bypass surgery. Anes Analg 1999;88:SCA 105.
transfusion requirements. Very few data are available on clopi- 25. Criado A, Juffe A, Carmona J, Otero C, Avello F. Ticlopidine as a dogrel and ticlopidine. Anti-glycoprotein (GP) IIb/IIIa agents hemorrhagic risk factor in coronary surgery. Drug Intell Clin may increase bleeding when surgery is required in proximity with their administration. Second, the common practice of 26. Installe E, Gonzalez M, Schoevaerdts JC, Tremouroux J. Preven- tion by ticlopidine of platelet consumption during extracorpore- withdrawing antiplatelet agents is now challenged because an al circulation for heart surgery and lack of effect on operative increased incidence of myocardial infarction has been reported and post-operative bleeding. J Cardiovasc Pharmacol 1981;3(6): in patients in whom treatment was interrupted. Third, aspirin should not be withdrawn for most vascular procedures and in 27. Renner C, Guilmet D, Curtet JM. [Ticlopidine in heart surgery several additional settings. When a definite increase in intra- with cardiopulmonary by-pass]. Nouv Presse Med 1980;9(43): operative bleeding is feared, or when surgical hemostasis is dif- ficult, aspirin, clopidogrel or ticlopidine can be replaced by 28. Tcheng JE, Ellis SG, George BS, Kereiakes DJ, Kleiman NS, Talley JD, et al. Pharmacodynamics of chimeric glycoprotein IIb/IIIa short-acting NSAIDS, given for a ten-day period and interrupt- integrin antiplatelet antibody Fab 7E3 in high-risk coronary ed the day before surgery. Platelet transfusion should only be angioplasty. Circulation 1994;90(4):1757-64.
given when overt bleeding is observed. Postoperatively, 29. Lemmer JH. Clinical experience in coronary bypass surgery for antiplatelet treatment should be resumed immediately after abciximab-treated patients. Ann Thorac Surg 2000;70(2 Suppl): Conclusion: Anesthesiologists should be aware of the indica-
30. Lincoff AM, LeNarz LA, Despotis GJ, Smith PK, Booth JE, Ray- mond RE, et al. Abciximab and bleeding during coronary tions, potential complications and means of substitution of surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evalu- Can J Anesth 2002; 49(Supplement): S26–35.
ation of Platelet IIb/IIIa Inhibition in STENTing. Ann Thorac Surg2000;70(2):516-26.
31. Gammie JS, Zenati M, Kormos RL, Hattler BG, Wei LM, Pellegrini RV, et al. Abciximab and excessive bleeding in patients undergo- Upcoming Scientific Meetings
ing emergency cardiac operations. Ann Thorac Surg1998;65(2):465-9.
32. Lemmer JH, Jr., Metzdorff MT, Krause AH, Jr., Martin MA, Okies JE, Hill JG. Emergency coronary artery bypass graft surgery in 44th National Congress of Anesthesia and
abciximab-treated patients. Ann Thorac Surg 2000;69(1):90-5.
33. Steinhubl SR, Kottke-Marchant K, Moliterno DJ, Rosenthal ML, Godfrey NK, Coller BS, et al. Attainment and maintenance of platelet inhibition through standard dosing of abciximab in dia- betic and nondiabetic patients undergoing percutaneous coro- nary intervention. Circulation 1999;100(19):1977-82.
34. Silvestry SC, Smith PK. Current status of cardiac surgery in the abciximab-treated patient. Ann Thorac Surg 2000;70(2 Suppl): Abstracts of Interest
Dr. Marie-France Guimond, Montreal, is responsible for the Antiplatelet agents in the perioperative period:
translation of this issue of Anesthesiology Rounds. Expert recommendations of the French Society of
Anesthesiology and Intensive Care (SFAR) 2001 –
Summary Statement.

Change of address notices and requests for subscriptions SAMAMA CM, BASTIEN O, FORESTIER F, ET AL., AND THE EXPERT GROUP. to Anesthesiology Rounds are to be sent by mail to P.O.
Purpose: Antiplatelet agents are administered to an increasing
Box 310, Station H, Montreal, Quebec H3G 2K8 or by number of patients. Preoperative treatment with these agents fax to (514) 932-5114 or by e-mail to info@snellmedical.
represents a major problem for the anesthesiologist. The com. Please reference Anesthesiology Rounds in your results of a French expert meeting on their perioperative man- correspondence. Undeliverable copies are to be sent to This publication is made possible by an educational grant from 2002 Department of Anesthesia, Faculty of Medicine, University of Montreal, which is solely responsible for the contents. The opinions expressed in this publication do not necessarily reflect those of
the publisher or sponsor, but rather are those of the authoring institution based on the available scientific literature. Publisher: SNELL Medical Communication Inc. in cooperation with the Department
of Anesthesia, Faculty of Medicine, University of Montreal. All rights reserved. The administration of any therapies discussed or referred to in Anesthesiology Rounds should always be consistent with the
recognized prescribing information in Canada. SNELL Medical Communication Inc. is committed to the development of superior Continuing Medical Education.

Source: http://www.bleedingweb.com/files/anesth05_02eng.pdf


Product Information Zaprinast CAS Registry No.: 37762-06-4 Formal Name: 3,6-dihydro-5-(2-propoxyphenyl)-7H- Synonyms: 2-(o-Propoxyphenyl)-8-azapurin-6-one, FW: 271.3 Purity: ≥98% Stability: Supplied as: Laboratory Procedures For long term storage, we suggest that zaprinast be stored as supplied at -20°C. It should be stable for at least one Zaprinast is supplie


Building reliable normal reference range, As an interpretation guide for clinical practices Clinical research team of Medicore Co., Ltd. Since Medicore Co., Ltd. completed the development of function of autonomic nervous system, which the SA-2000, the first HRV analyzer model in 2,000, we, accelerated various HRV studies to find out the by organizing the research team from neuropsychiatr

Copyright © 2010-2014 Online pdf catalog