Emergency Coronary Artery Bypass Surgery in the Era of Glycoprotein IIb/IIIa Receptor Antagonist Use

Abstract The use of intravenous glycoprotein (GP) IIb/IIIa platelet receptor antagonists in the management of patients with acute coronary syndrome or those undergoing percutaneous coronary intervention (PCI) has become increasingly common in recent years. There are three GP IIb/IIIa receptor antagonists currently available for clinical use. Patients on GP IIb/IIIa receptor antagonists who require emergency surgical revascularization may be at increased risk for excessive peri‐and postoperative bleeding. The duration of action of eptifibatide and tirofiban are short because they bind reversibly to the GP IIb/IIIa receptor and have a short half‐life. Therefore, within a relatively short time after discontinuation of these agents, surgery can be performed with little or no increased risk of bleeding and without the need for additional hemostatic measures. Abciximab has a short plasma half‐life but a long duration of action due to its high‐affinity binding of GP IIb/IIIa receptors. Early retrospective studies demonstrated a higher incidence of major bleeding and requirement for blood transfusion, especially in those undergoing surgery within 12 hours of the discontinuation of abciximab. However, platelet transfusion has been shown to successfully reduce the incidence of these complications. The current evidence therefore indicates that, with appropriate measures, urgent surgical revascularization can be safely performed in patients who have received a GP IIb/IIIa receptor antagonist with little added risk. The benefits of these agents in the treatment of patients with an acute coronary syndrome or undergoing PCI are not obviated by the need for emergency bypass surgery.     

Immediate coronary artery bypass surgery after platelet inhibition with eptifibatide: results from PURSUIT. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrelin Therapy

BACKGROUND: The platelet GP IIb/IIIa inhibitor eptifibatide improves outcomes in patients with acute coronary syndromes. Patients requiring emergent coronary artery bypass grafting, however, may be at increased risk for bleeding if exposed to eptifibatide. Data from the PURSUIT trial were reviewed to assess this risk in patients undergoing coronary surgery immediately after exposure to eptifibatide. METHODS: In PURSUIT, 10,948 patients who presented with non-ST segment elevation acute coronary syndromes were prospectively randomized to receive eptifibatide (180 microg/kg bolus plus 2 microg/kg/min infusion) or placebo. A total of 78 patients underwent immediate coronary artery bypass surgery within 2 hours of cessation of study drug (placebo, n = 46; eptifibatide, n = 32). Clinical outcome, bleeding, and transfusion requirements within this subset were examined. RESULTS: Major bleeding was not different between groups, occurring in 64% of patients receiving placebo and 63% of patients receiving eptifibatide. The incidence of blood transfusion was similar as well (57% vs 59%). Postoperative thrombocytopenia occurred less often after eptifibatide exposure. Perioperative myocardial infarction was significantly reduced in patients who received eptifibatide (46% vs 22%, p < 0.05). There was no difference in perioperative stroke (2.2% vs 6.3%) or mortality (6.3% vs 6.5%). CONCLUSIONS: Patients may safely undergo coronary artery bypass surgery within 2 hours of discontinuation of eptifibatide. Eptifibatide infusion in the immediate preoperative period had no adverse clinical effects, but did significantly decrease the incidence of perioperative myocardial infarction. Additionally, platelet counts after surgery were higher in the group of patients who received eptifibatide, perhaps indicative of a platelet-sparing effect during cardiopulmonary bypass.     

Pharmacologic preservation of the hemostatic system during cardiac surgery.

Bleeding after cardiac surgery remains a major potential problem. Numerous pharmacologic approaches to attenuating hemostatic system activation in cardiac surgery patients have been studied to further improve patient management. Therapeutic approaches studied include inhibiting thrombin generation or activation, preserving platelet function, and decreasing the need for transfusion of allogeneic blood products. Pharmacologic approaches to reduce bleeding and transfusion requirements in cardiac surgery patients are based on either preventing or reversing the defects associated with the CPB-induced coagulopathy. The increasing use of platelet inhibitors (clopidogrel and IIb/IIIa receptor antagonists) and new anticoagulants (low-molecular weight heparins, pentasaccharide, recombinant hirudin, bivalirudin, and argatroban) also pose interesting problems in managing cardiac surgery patients. Aprotinin and lysine analogues (epsilon-aminocaproic acid and tranexamic acid) have become mainstay therapeutic agents to prevent bleeding and the potential need for allogeneic transfusion. Newer therapies that are important to consider include the potential of recombinant activated factor VIIa as a therapy for refractory bleeding after cardiac surgery.     

Antiplatelet agents and perioperative bleeding

Purpose

To briefly review the risks, in patients presenting for surgery, associated with the available antiplatelet agents, and to present the principles that should guide the evaluation of these risks and how to manage them.

Methods

A narrative review of the current medical literature in English and French.

Main findings

Antiplatelet agents [mainly acetylsalicylic acid, clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors] are used increasingly to prevent arterial thrombosis. Clinicians are confronted with the hemorrhagic risk associated with the continuation of antiplatelet agents throughout surgery or, conversely, with the thrombotic risk associated with their discontinuation. Most experts recommend surgery while maintaining acetylsalicylic acid for most vascular procedures and in several additional settings where the bleeding risk has been shown (or is likely) to be low. It is commonly recommended that clopidogrel be stopped five days before surgery to allow replacement of half the platelet pool. This approach has been associated with thrombotic events in patients waiting for urgent myocardial revascularization. In this context, aprotinin may reduce blood losses and transfusion requirements. Withdrawal of the competitive GPIIb/IIIa inhibitors at the beginning of surgery will decrease the risk of bleeding, less so for abciximab owing to its avid binding to platelet receptors. Platelets should not be transfused prophylactically, but only to those few patients with abnormal bleeding thought to be related to the persisting effect of antiplatelet therapy.

Conclusions

Unfortunately, data regarding the management of antiplatelet agent-treated patients undergoing surgery, especially non-cardiovascular, are scarce. Further clinical trials must be conducted to guide the clinical management of these patients.

     

Inhibitors of the platelet receptor glycoprotein IIb-IIIa and complications during percutaneous coronary revascularization. Management strategies for the cardiac surgeon.

Platelet-mediated thrombosis has a pivotal role in the pathophysiology of acute ischemic coronary syndromes (AICS) and the acute complications of percutaneous coronary interventions. Because cross-linking of the activated platelet receptor glycoprotein (GP) IIb-IIIa by plasma fibrinogen represents the final common pathway to coronary thrombus formation, several GP IIb-IIIa inhibitors have been developed as a potentially more effective antithrombotic therapy than agents currently used for this purpose, namely aspirin and heparin. However, use of GP IIb-IIIa inhibitors in patients with AICS and those scheduled for percutaneous coronary interventions may increase the risk of serious clinical and bleeding events among patients who require emergency or urgent bypass surgery. This review describes clinical experience with various GP IIb-IIIa inhibitors and suggests management strategies for patients undergoing emergency or urgent bypass surgery shortly after treatment with GP IIb-IIIa inhibitors.     

Local glycoprotein IIb/IIIa receptor inhibitor delivery from the pump surface attenuates platelet adhesion in continuous flow ventricular assist devices

Shear-induced platelet activation (SIPA) has been identified to induce platelet adhesion and thrombus formation in continuous flow left ventricular assist devices (LVAD). Platelet glycoprotein (GP) IIb/IIIa receptor inhibitors are effective to prevent SIPA. However, systemic GP IIb/IIIa receptor inhibitor application is associated with severe bleeding complications. The aim of the study was to evaluate (i) the feasibility of absorption and elution of the GP IIb/IIIa receptor blocker TAK-029 from the Ti6Al4V surface of the pump; and (ii) the effect of local GP IIb/IIIa receptor blocker delivery regarding platelet adhesion on the surface of a continuous flow VAD model. Saturating concentrations of TAK-029 were adsorbed on the surface of a centrifugal pump. Whole human blood was perfused in circulatory mock loops using untreated (control), albumin-coated, or TAK-029-coated pumps. Peripheral resistance of the circulatory systems were adjusted accordingly to generate 5 L flow per min with impeller rotational speeds of 3500 (high-shear group) and 1500 rpm (low-shear group), respectively. Platelet adhesions on the respective impellers were quantified by ELISA and scanning electron microscopy (SEM). TAK-029 elution and half-life time were determined by ELISA. Compared with control, albumin-coated pumps showed 64 and 20% less platelet adhesions in the high- and low-shear group, respectively. TAK-029 coated pumps reduced platelet adhesion by additional 33 and 65%, respectively, compared with the albumin group. Elution of TAK 029 was initially very rapid and continued slowly. The results show that it is possible to adsorb and elute a small molecular weight GP IIb/IIIa receptor blocker from the pump surface. This drug elution reduced platelet adhesion on the pump significantly. Further studies are necessary to find a suitable drug bonding that will prolong the antiplatelet effect and preclude any bleeding complication caused by this procedure.     

Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting.

BACKGROUND: The platelet glycoprotein IIb/IIIa inhibitor tirofiban hydrochloride improves outcome in patients with acute coronary syndrome. Nevertheless, a considerable number of patients require emergency or urgent coronary artery bypass grafting and may be at increased risk of postoperative bleeding after treatment with this molecule. The aim of this study is to evaluate the incidence of bleeding complications among patients undergoing bypass grafting after treatment with tirofiban. METHODS: We investigated the influence of the molecule on postoperative bleeding after cardiac surgery, comparing 2 groups of patients undergoing emergency or urgent coronary artery bypass grafting: group A (n = 20) received tirofiban, and group B (n = 68) received conventional therapy with intravenous heparin up until the operation. A total of 88 patients underwent coronary artery bypass surgery within 2 hours of ceasing the hemodynamic study. Clinical outcome, chest tube outputs, bleeding complications, transfusion requirements, platelet and hemoglobin counts, and clinical complications were examined. RESULTS: Bleeding differences were noted between the 2 groups at 8, 16, and 24 hours postoperatively. The incidence of blood, platelet, and fresh frozen plasma transfusions was higher in the control group. Postoperative thrombocytopenia was preserved in group A (199.5 +/- 70.4 vs 150.6 +/- 33.4 10(3)/mL, P <.01). No significant differences were noted between the 2 groups in the incidence of perioperative myocardial infarction, but significant differences were noted in enzyme levels, length of stay in the intensive care unit, and length of stay in the hospital. No deaths were observed. Hospital morbidity was increased in group B because of factors that were not apparently linked with tirofiban infusion. CONCLUSIONS: Patients may safely undergo coronary artery bypass surgery after treatment with tirofiban hydrochloride. This molecule, administered in the immediate preoperative period, has no adverse clinical effects and does not seem to negatively influence the incidence of perioperative myocardial infarction. Although extracorporeal circulation can modify platelet numbers and function, our ongoing data could show significant reduction in the loss of platelets induced by cardiopulmonary bypass, minor postoperative bleeding, and a minor transfusion requirement in general.     

Impact of clopidogrel in coronary artery bypass grafting.

OBJECTIVE: Clopidogrel has become the standard of care to prevent thrombotic complications following cardiological interventions, in particular intracoronary stenting. In addition, patients with aspirin intolerance and those with carotid and peripheral vascular disease are also increasingly treated with clopidogrel. Platelet inhibition may become a concern for hemostasis in patients treated with clopidogrel who need emergency and undelayed surgery. METHODS: We prospectively analyzed the intra- and postoperative outcome of 505 consecutive patients who underwent isolated CABG and compared two groups: those with clopidogrel exposure until 72 h prior to surgery (n = 136) with those without exposition to clopidogrel (n = 369). Patients undergoing emergency surgery because of failed PTCA and cardiogenic shock, associated valvular surgery, redo-CABG, and those with additional platelet IIb/IIIa receptor inhibitor exposure were excluded. Patients who received aspirin and/or heparin treatment prior to surgery were not excluded. Results: Patients who received clopidogrel had a higher prevalence of angina class III or IV (67 vs 39%, P < 0.01), received more often revascularization within 48 h (41 vs 14%, P = 0.02), and had received more frequently stenting (57 vs 13%). Chest tube drainage was significantly increased during the first 24 h following CABG in the group of patients who had clopidogrel treatment (1485 vs 780 ml, P = 0.003) These patients also required more transfusion of platelets and fresh frozen plasma. Overall re-exploration rate because of bleeding was significantly higher in the clopidogrel group (5.9 vs 1.2%, P < 0.01). Platelets transfused before chest closure had a beneficial effect on preservation of the hemostasis. CONCLUSIONS: Clopidogrel exposure 3 days or less prior to CABG surgery significantly increases the risk of postoperative bleeding, the need for perioperative transfusion and the incidence of re-exploration. Surgery should be performed using standard heparinization and anti-fibrinolytic strategies but aggressive correction of platelets dysfunction is required before chest closure.     

The effect of intravenously administered magnesium on platelet function in patients after cardiac surgery.

After cardiac surgery, magnesium is often administered for prophylaxis and treatment of cardiac arrhythmias. Magnesium, however, inhibits platelet function in vitro and in healthy volunteers. We performed a randomized, blinded, and placebo-controlled study to investigate the effect of magnesium on platelet function in patients after cardiac surgery. We studied patients who underwent uneventful coronary revascularization with cardiopulmonary bypass on the first postoperative day. Before and after an infusion of either 5.4 mmol magnesium (n = 19) or saline (n = 20), platelet function was investigated by means of in vitro bleeding time, platelet aggregation, and flow-cytometric assays. In addition, to investigate platelet function in vitro, 1, 5, and 10 mM magnesium were added to platelet-rich plasma before and 24 h after surgery in 30 patients. Compared with the control group, magnesium prolonged the in vitro bleeding time (22%) and inhibited ADP- and collagen-induced platelet aggregation (13% and 17%), platelet P-selectin expression (18%), and the binding of fibrinogen to the platelet glycoprotein IIb/IIIa receptor (10%). Magnesium also led to significant dose-dependent inhibition of platelet aggregation (19%), P-selectin expression (14%), and fibrinogen binding (11%) before and after surgery in vitro. Although the antithrombotic effect of magnesium may be beneficial in patients after coronary revascularization, large-dose magnesium therapy should be carefully considered in patients with impaired platelet function and co-existing bleeding disorders. IMPLICATIONS: In a randomized, blinded, placebo-controlled study of patients 24 h after coronary artery bypass grafting, IV administered magnesium inhibited platelet function in vitro and in vivo.     

Some new perspectives in heparin-induced thrombocytopenia type II.

We conclude that HIT II is a serious complication, particularly in patients undergoing cardiovascular surgery that involves CPB. New tests might contribute to the earlier diagnosis of this disease. However, the reduction of immunization by the use of alternative anticoagulants whenever possible seems to be the most effective strategy for the reduction of HIT II-associated complications. If HIT II is diagnosed. r-hirudin is effective as an acute therapy (especially in combination with GP IIb/IIIa inhibitors) and also for further anticoagulation. If patients must undergo CPB, all current alternative anticoagulation concepts are associated with relevant drawbacks that put the patient at an increased risk for post-operative bleeding and/or CPB thrombosis. Currently, r-hirudin is most probably the best option for this purpose. However, when there is impaired renal function, the persistent anticoagulant effect is associated with hemorrhage. Further studies must evaluate whether extracorporeal elimination procedures, such as hemofiltration or plasmapheresis, are effective in avoiding such complications. Otherwise, the combination of UFH with a potent antiplatelet agent, especially with short-acting GP IIb/IIIa antagonists, is an attractive alternative.     

Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors?

Platelet inhibitors, especially the glycoprotein (GP) IIb/IIIa receptor antagonists, have demonstrated their effectiveness in reducing the acute ischemic complications of percutaneous coronary intervention (PCI) and in improving clinical outcomes in patients with acute coronary crisis. Three common platelet inhibitors observed in emergent cardiopulmonary bypass (CPB) for failed PCI are abciximab, eptifibatide, and tirofiban. An in vitro model was constructed in two parts to determine whether platelet aggregation inhibition induced by platelet inhibitors would be demonstrated by the Thrombelastograph (TEG) monitor when compared with baseline samples with no platelet inhibitor. In part A, 20 mL of fresh whole blood was divided into four groups: group I = baseline, group A = abcix-imab microg/mL, group E = eptifibatide ng/mL, and group T = tirofiban ng/mL. Platelet inhibitor concentrations in whole blood were derived starting with reported serum concentrations with escalation to achieve 80% platelet inhibition using the Medtronic hemoSTATUS and/or Lumi-aggregometer. A concentration range determined by our in vitro tests were chosen for each drug using concentrations achieving less than, equal to, or greater than 80% platelet inhibition. In part B, TEG analysis was then performed using baseline and concentrations for each drug derived in part A. Parameters measured were clot formation reaction time (R), coagulation time (K), maximum amplitude (MA) and alpha angle (A). Groups E1000 and E2000 extended R over control by 37% and 23%, respectively (p = 0.01 and 0.03). Groups E1000 and E2000 increased K times by 45% and 58% (p = .02 and .04). T160 samples prolonged K by 20% (p = 0.01). The angle or clot strength (A) was decreased in groups T160 and E1000 by 23% (+ 7.06 SD) and 18% (+ 11.23 SD), respectively (p = 0.001 and 0.01). The MA decrease was statistically significant in the T160, E1000 and E2000 by 9%, 6% and 13% respectively (p = 0.01). Samples treated with abciximab were comparable to control values for all parameters measured. Although statistical significance could be demonstrated with some parameters, sensitivity was only observed at increased doses and was not seen with all agents tested. In our in vitro model, the TEG monitor was unable to demonstrate clinically significant differences in platelet function and may not be reflective of platelet function in samples which have been treated with these GP IIb/IIIa inhibitors.     

Off-pump coronary artery bypass grafting. Excellent results in a group of selected high-risk patients.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCABG) has assumed an increasing role in many surgical practices. The ideal candidate has not been defined, but high-risk patients seem to benefit most when cardiopulmonary bypass (CPB), aortic cross clamping and cardioplegic arrest are avoided. METHODS: Fourteen high-risk patients (age 52 to 81 years, 1 female, EF 44%+/-8, Parsonnet score 23+/-4) were studied. They presented with acute coronary syndroms on platelet glycoprotein IIb/IIIa antagonists, acute myocardial infarction, worsening renal failure, decompensating ischemic cardiomyopathy, religious beliefs and denial of blood transfusion, and severe peripheral/cerebrovascular disease (total bilateral internal carotid artery occlusion and/or >90% stenosis). These patients underwent OPCABG via sternotomy with the intention of complete coronary revascularization. RESULTS: An average of 2.3 grafts/patient were performed and the posterior descending artery (PDA) and marginal branches of the circumflex artery (LCX) were grafted in 79% of the patients. There were 3 events of intraoperative cardiac arrest precipitated by occlusion of right coronary artery (RCA) or positioning a cardiomegaly heart leading to immediate intravascular shunting (2) and/or conversion to CPB (1). One patient was converted to CPB and graft revision (intraoperative ultrasound and probing). The mortality rate was 0% and one stroke was observed on post-operative day 1. Coronary angiography (n=6) showed no significant stenosis. CONCLUSIONS: OPCABG complete revascularization is feasible in high-risk patients with low morbidity and mortality and excellent early RESULTS: OPCABG may be indicated in patients on platelet receptor antagonists preventing bleeding complications. Cardiomegaly can cause difficult off-pump LCX and PDA exposure and stabilization. RCA grafting off-pump is less tolerated and PDA grafting is preferred. High-risk patients for CPB are the ones who may benefit the most from OPCABG.     

Glycoprotein IIb/IIIa receptor inhibitor attenuates platelet aggregation induced by thromboxane A2 during in vitro nonpulsatile ventricular assist circulation

A recent development in antithrombotic research allows the inhibition of platelet aggregation via protection of the glycoprotein IIb/IIIa receptor on the platelet membrane. We hypothesized that a GP IIb/IIIa receptor inhibitor would inhibit thromboxane-induced platelet aggregation during circulation in our in vitro ventricular assist device (VAD) circuit and preserve long-term platelet function. Twenty-one in vitro nonpulsatile centrifugal VAD circuits were simulated for 4 days using 450 ml of fresh human whole blood with or without glycoprotein IIb/IIIa receptor inhibitor (tirofiban). Platelet aggregation and degranulation were measured in whole blood induced by ristocetin, collagen, ADP, and thromboxane A2 (TXA2). The tirofiban-treated group preserved the platelet count and tended to exert these beneficial effects by inhibiting pathologic platelet aggregation induced by TXA2, collagen, and ADP as well as degranulation. Tirofiban may be useful in preserving platelet number and function during clinical VAD use.     

Prediction of the excessive perioperative bleeding in patients undergoing coronary artery bypass grafting: role of aspirin and platelet glycoprotein IIIa polymorphism

OBJECTIVE: The presence of the glycoprotein IIIa allele PlA2 is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin, which could favor coronary thrombosis. We wondered whether PlA1/A2 genetic polymorphism could affect the postoperative bleeding in patients undergoing coronary artery bypass grafting. We also aimed to assess the effects of aspirin pretreatment and to ascertain the value of platelet function studies as predictors of postoperative bleeding. METHODS: In a randomized, double-blind study, patients undergoing coronary artery bypass grafting were pretreated with a 150-mg dose of aspirin orally 12 and 3 hours before surgery (n = 51, 41 elective) or with placebo (n = 51, 43 elective). The hemostasis was monitored by Simplate (bioMérieux, Inc, Durham, NC) bleeding time and capillary closure time (platelet function analyzer PFA 100; Sysmex UK Ltd, Milton Keynes, United Kingdom). Postoperative bleeding and blood products transfusions were recorded. The glycoprotein IIIa polymorphism was analyzed. RESULTS: Bleeding was significantly greater in PlA1 homozygotes from control group. Blood loss was significantly greater (by 25%) in aspirin group. The volume of blood products transfusions in aspirin patients was significantly larger (by 137%). When subjects were stratified accordingly to blood platelet glycoprotein IIb/IIIa genotype, in the aspirin group PlA2 carriers had greater blood loss than PlA1 homozygotes (1858 +/- 932 mL vs 1216 +/- 525 mL, P < .05). CONCLUSION: PlA1 homozygotes normally had a greater risk of perioperative bleeding. Capillary closure time had no advantage relative to Simplate bleeding time in predicting postoperative blood loss. Aspirin pretreatment revealed no beneficial effects and resulted in increased postoperative bleeding and requirement for blood product transfusions after coronary artery bypass grafting in patients with stable angina. It was most unfavorable for PlA2 carriers.     

The GP IIb/IIIa inhibitor abciximab (ReoPro) decreases activation and interaction of platelets and leukocytes during in vitro cardiopulmonary bypass simulation.

OBJECTIVE: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and increases expression of the platelet activation marker P-selectin which mediates binding of platelets to leukocytes. Inhibition of the platelet GP IIb/IIIa receptor during CPB has been shown to protect platelets without increasing bleeding complications and is assumed to reduce the inflammatory response. The aim of this study was to investigate the effect of the GP IIb/IIIa inhibitor abciximab (ReoPro) on the function and interaction of platelets and leukocytes during experimental CPB. METHODS: Heparinized (3 U/ml) fresh whole blood of healthy volunteers was treated before continuous in vitro circulation in a well established CPB model with 3.2 microg/ml abciximab (n=6) or left untreated as control (n=6). Measurements were made before (baseline) and after 30 and 60 min of circulation and comprised: percentage of platelets expressing P-selectin and percentage of platelet-bound leukocytes (flow cytometry), release of the leukocyte activation marker PMN-elastase (ELISA), and platelet and leukocyte counts. RESULTS: Abciximab almost completely prevented a CPB-induced increase of platelet P-selectin and platelet-leukocyte binding after 30 and 60 min of circulation, and significantly inhibited release of PMN-elastase after 30 min of circulation. Furthermore, abciximab significantly inhibited a CPB-induced decrease of platelet and leukocyte counts. CONCLUSIONS: Abciximab inhibits CPB-induced activation, interaction and consumption of platelets and leukocytes in vitro. GP IIb/IIIa inhibition should be considered as a promising approach not only to conserve platelet function but also to inhibit pro-inflammatory events during CPB in vivo.     

Neue Thrombozytenhemmstoffe

The antiplatelet action of acetylsalicylic acid is mostly used in vascular medicine. In the meantime two other classes of platelet inhibiting agents have been introduced. Thieopyridines (Ticlyridin, Clopidogrel) have been shown to inhibit ADP induced platelet aggregation with persistence of this effect for several days after withdrawal. The short acting intravenous Glycoprotein IIb/IIIa inhibitors considerably improved the management of acute coronacy syndrome. The above mentioned compounds may be applied in combination at least for some days, and heparins are given in addition. Mainly the bleeding complications are to be taken into account especially if patients have to undergo emergency interventions. Hemodialysis or platelet concentrates are recommended to antagonise the antiplatelet effects immediately.     

Antiplatelet agents in the perioperative period: expert recommendations of the French Society of Anesthesiology and Intensive Care (SFAR) 2001--summary statement.

PURPOSE: Antiplatelet agents are administered to an increasing number of patients. Preoperative treatment with these agents represents a major problem for the anesthesiologist. The results of a French expert meeting on their perioperative management are reported. METHODS: Responses to questions formulated by the Organizing Committee were drafted by a group of experts and reviewed by a multidisciplinary. Reading Committee. Recommendations were classified (grade) according to the evidence level of the studies supporting them. PRINCIPAL FINDINGS: First, antiplatelet agents have a variable effect on hemostasis as far as bleeding risk is concerned. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) increase intra- and postoperative bleeding moderately, but not transfusion requirements. Very few data are available on clopidogrel and ticlopidin. Anti-glycoprotein (GP) IIb/IIIa agents may increase bleeding when surgery is required in proximity with their administration. Second, the common practice of withdrawing antiplatelet agents is now challenged because an increased incidence of myocardial infarction has been reported in patients in whom treatment was interrupted. Third, aspirin should not be withdrawn for most vascular procedures and in several additional settings. When a definite increase in intraoperative bleeding is feared, or when surgical hemostasis is difficult, aspirin, clopidogrel or ticlopidine can be replaced by short-acting NSAIDS, given for a ten-day period and interrupted the day before surgery. Platelet transfusion should only be given when overt bleeding is observed. Postoperatively, antiplatelet treatment should be resumed immediately after surgery (first six hours). CONCLUSION: Anesthesiologists should be aware of the indications, potential complications and means of substitution of these agents.     

Clopidogrel-related refractory bleeding after coronary artery bypass graft surgery: a rationale for the use of coagulation factor concentrates?

Clopidogrel, an irreversible ADP-receptor antagonist, inhibits platelet aggregation mediated by reduced activation of glycoprotein receptor IIb/IIIa. Clopidogrel in combination with aspirin has been shown to be superior to aspirin alone for treating unstable angina, but clopidogrel recipients have shown increases in blood loss, transfusion requirements, and rate of reoperation after cardiac surgery. We describe a patient who had taken clopidogrel 75 mg daily until the day prior to coronary artery bypass graft surgery. Severe postoperative bleeding developed and was refractory to conventional hemostatic therapy consisting of 19 units of packed red blood cell concentrates, 16 of fresh frozen plasma, 8 of platelet apheresis concentrates plus high-dose treatment with aprotinin (500.000 kallikrein-inhibiting units/h) and administration of 0.3 microg/kg 1-deamino-8-D-arginine vasopressin (DDAVP). Two reoperations were performed, but surgical hemostasis was not achieved, so 100 microg/kg recombinant activated factor VII was applied to generate sufficient thrombin to stop the bleeding. This treatment approach reduced the bleeding. Then, to promote clot formation and firmness, 2 g of fibrinogen and 1250 IU of factor XIII were administered, and the bleeding finally stopped. No further transfusions were required, and the patient was discharged from the hospital on day 10 after the operation. This case suggests that in clopidogrel-related bleeding refractory to conventional hemostatic therapy, hemostasis may be achieved by a stepwise administration of coagulation factor concentrates.     

Emergency cardiac surgery in patients with acute coronary syndromes: a review of the evidence and perioperative implications of medical and mechanical therapeutics

Patients with acute coronary syndromes who require emergency cardiac surgery present complex management challenges. The early administration of antiplatelet and antithrombotic drugs has improved overall survival for patients with acute myocardial infarction, but to achieve maximal benefit, these drugs are given before coronary anatomy is known and before the decision to perform percutaneous coronary interventions or surgical revascularization has been made. A major bleeding event secondary to these drugs is associated with a high rate of death in medically treated patients with acute coronary syndrome possibly because of subsequent withholding of antiplatelet and antithrombotic therapies that otherwise reduce the rate of death, stroke, or recurrent myocardial infarction. Whether the added risk of bleeding and blood transfusion in cardiac surgical patients receiving such potent antiplatelet or antithrombotic therapy before surgery specifically for acute coronary syndromes affects long-term mortality has not been clearly established. For patients who do proceed to surgery, strategies to minimize bleeding include stopping the anticoagulation therapy and considering platelet and/or coagulation factor transfusion and possibly recombinant-activated factor VIIa administration for refractory bleeding. Mechanical hemodynamic support has emerged as an important option for patients with acute coronary syndromes in cardiogenic shock. For these patients, perioperative considerations include maintaining appropriate anticoagulation, ensuring suitable device flow, and periodically verifying correct device placement. Data supporting the use of these devices are derived from small trials that did not address long-term postoperative outcomes. Future directions of research will seek to optimize the balance between reducing myocardial ischemic risk with antiplatelet and antithrombotics versus the higher rate perioperative bleeding by better risk stratifying surgical candidates and by assessing the effectiveness of newer reversible drugs. The effects of mechanical hemodynamic support on long-term patient outcomes need more stringent analysis.     

Perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to coronary artery bypass grafting with cardiopulmonary bypass

Glanzmann's thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.