Ann Thorac Surg 2000;70:S12-S19
© 2000 The Society of Thoracic Surgeons
Current status of cardiac surgery in the abciximab-treated patient
Scott C. Silvestry, MDa,
Peter K. Smith, MDa
a Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
Address reprint requests to Dr Smith, Duke University Medical Center, Duke South Blue Zone, Room 4532, Durham, NC 27710
e-mail: smith058{at}mc.duke.edu
Presented at the "Managing the Patient Receiving Platelet Inhibitors in Cardiac Surgery" Roundtable Discussion, San Antonio, TX, Jan 22–23, 1999.
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Abstract
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Background. Early surgical experience with abciximab and other glycoprotein (GP) IIb/IIIa receptor antagonists suggested a tendency toward excessive bleeding in patients treated with these agents. With increased use of GP IIb/IIIa inhibitors, cardiac surgeons have become aware of their hazards, as well as potential benefits, during and after cardiac surgery. Although published experience with the GP IIb/IIIa inhibitor abciximab is limited in scope, it suggests management guidelines for urgent coronary artery bypass grafting in abciximab-treated patients. As more urgent and elective surgical data are presented, a clearer picture of true bleeding risk will evolve.
Methods. Two large retrospective studies examining reexploration for postoperative bleeding have identified risk factors, including advanced age, preoperative renal dysfunction, and operation/reoperation other than coronary artery bypass grafting. Other risk factors for transfusion requirement and increased morbidity and mortality are emergent operation, postoperative coagulopathy, and prolonged bypass time.
Results. To minimize real and perceived bleeding effects, some authors have suggested delaying operation until platelet function has normalized, employing platelet transfusion in patients in whom delay is not possible, and exacting heparin management during cardiopulmonary bypass. Later reports have not noted increased bleeding when incorporating these modifications plus early platelet transfusion, if required. Further experience with abciximab removal and reversal may also ultimately reduce or eliminate excess transfusion requirements.
Conclusions. Surgeons should work closely with perfusionists and anesthesiologists on issues of heparinization in the abciximab-treated patient. The apparent paradox of preserved platelet numbers and depressed platelet function with abciximab use has led to speculation about a role for this agent and other shorter-acting GP IIb/IIIa inhibitors for "platelet anesthesia" during cardiopulmonary bypass. With careful surgical care, GP IIb/IIIa receptor antagonists can maintain and improve beneficial outcomes.
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Introduction
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The documented benefits of abciximab (c7E3) and other platelet glycoprotein (GP) IIb/IIIa receptor antagonists [1–7] have defined a primary therapeutic role for these drugs in the treatment of medium- and high-risk patients with unstable coronary syndromes (Fig 1) [8]. Their widespread therapeutic use has increased the exposure of the cardiac surgeon to the spectrum of GP IIb/IIIa effects in urgent and emergent cardiac surgical patients. Although the overall incidence of emergency coronary surgery was decreased in most trials, the early reported surgical experience suggested a tendency toward excessive bleeding in patients treated with these agents, as well as an unknown effect on surgical outcome and long-term morbidity.
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Fig 1. Treatment algorithm for angina and myocardial infarction. (Adapted with permission from Zaacks and colleagues [8].)
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Cardiac surgeons must avoid exposing patients to preventable postoperative bleeding and thus to the threat of mediastinal tamponade, blood product and donor exposure, and repeat surgery for reexploration. It is also important to simultaneously reduce the hazard of perioperative thrombotic events through the judicious use of anticoagulants. Resolving these conflicting goals has been an ongoing challenge as new, more effective agents have been developed in an effort to improve the results of percutaneous revascularization procedures.
Abciximab represents the most recent challenge, and a formidable one. The benefits of this powerful, specific platelet antagonist will be reviewed elsewhere in this monograph. This article will review surgical experience with postoperative bleeding, its risks, and specific experience with abciximab.
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Risks of postoperative bleeding
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Increased use of abciximab has made cardiac surgeons aware of the real hazards of GP IIb/IIIa inhibitor use, as well as the potential benefits. Bleeding related to the use of these antiplatelet agents, both during and after cardiac surgery, has raised concerns about increased perioperative comorbidity, as well as adverse effects on surgical outcome. In addition to these dangers during emergent and urgent coronary artery bypass grafting (CABG), the therapeutic benefit of abciximab may broaden the indications for percutaneous intervention [1–7] and reintervention [9]. That change in treatment strategy may alter both the emergent and urgent CABG rate by further altering primary, elective surgical indications.
Abciximab has been associated with a moderate increase in all bleeding complications associated with percutaneous intervention (PTCA/PTCS) [2, 10–12]. Blankenship and coworkers described increased bleeding during surgical intervention in the abciximab-treated patients in the EPIC trial [12]. Logistic regression analysis demonstrated that abciximab was an independent predictor of bleeding and was associated with a 1- to 4-day increase in length of hospital stay [12]. Subsequent reduction in bleeding risk was noted in follow-up when concomitant heparin dosage was reduced in the EPILOG trial, but this modification negated the reduction in revascularization observed at 6 months in the EPIC trial, suggesting a need for full heparinzation to achieve full therapeutic effect [6].
Bleeding complications associated with abciximab in cardiac surgical patients varied in clinical trials and in individual series. Although several small series reported significant increases in blood loss, chest tube drainage, and transfusion needs [10, 11, 13–16], several of the large clinical trials did not report these events [1, 11]. Variability in the observed bleeding risk of abciximab may be attributable to differences in administration (bolus, bolus plus infusion), heparin use (low and full dose, preoperative and intraoperative), time interval between dosing and surgery, surgical variability, and distribution of other concomitant risk factors for bleeding.
The need to explore a postoperative patient with excessive bleeding and normal coagulation is clear. Assessing postoperative bleeding for potential technical causes in the setting of a profound hemostatic defect can be frustrating and dangerous. In a recent study of 2,221 cardiac surgical patients [15], the incidence of reexploration for bleeding/tamponade was 3.8%. An identifiable source of bleeding was found in 57 of the 85 patients (67%), but concurrent coagulopathy was common (45 patients) [15]. Booth and coworkers reported a trend toward a higher, but not statistically significant, reexploration rate in abciximab-treated patients compared with placebo [14]. The abciximab-treated patients had an increased percentage of other than "diffuse ooze" bleeding, suggesting an increased technical complication rate in a background of coagulopathy [14]. Last, although tamponade is usually associated with excessive bleeding, even mild postoperative bleeding can cause early resternotomy when associated with coagulopathy and hemodynamic compromise in low-risk groups [16].
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Surgical experience with abciximab
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A summary of published surgical experience, transfusions, and mortality in abciximab-treated patients undergoing emergent CABG for failed percutaneous revascularization is presented in Table 1. Overall, the published experience is limited in scope and consists predominantly of small series without controls. The cumulative experience represented by these series suggests management guidelines for urgent CABG in the abciximab-treated patient. The experience is not sufficient to evaluate the therapy in the context of overall effectiveness of GP IIb/IIIa on the population of patients with coronary artery disease [17].
The majority of published reports on abciximab discuss emergency surgical intervention in patients. As more data are presented describing urgent and elective surgical revascularization with intercurrent GP IIb/IIIa blockade, a clearer picture of the true bleeding risk will evolve. No well-controlled study has shown an increase in morbidity and mortality of the population at risk, although some authors have suggested that a lack of suitable index groups has made it impossible to accurately gauge the incremental increase in morbidity in abciximab-treated patients undergoing emergent CABG [17, 18].
Cardiac tamponade
Postoperative cardiac tamponade represents a potentially fatal complication of cardiac surgery. The exact incidence of postoperative tamponade is unknown, but estimates range from 0.5% to 0.8% [19–23] of postoperative CABG patients. Keck and coworkers have identified renal insufficiency, age, and chest tube drainage as risk factors for cardiac tamponade in the postoperative period [21]. In addition, Malouf and coworkers have shown an association between excessive anticoagulation, large pericardial effusion, and late tamponade [24]. Moulton and coworkers [16] identified a subgroup of patients with minimal or moderate postoperative bleeding requiring resternotomy for tamponade with significant increases in adverse outcome as compared with nonresternotomy patients with equal bleeding. Early and late cardiac tamponade is associated with increased morbidity and mortality [16, 24, 25]. Thus, the excessive bleeding seen in abciximab-treated patients has raised concern over the potential for increased risk of postoperative cardiac tamponade and resultant morbidity and mortality. The EPIC trial [11] reported an increased incidence of pericardial tamponade in one abciximab-treated group compared with placebo, a difference that was not statistically significant because of the small sample size. Other data regarding postoperative tamponade in the clinical trials of abciximab are scarce.
Exploration: impact on outcome
Repeat sternotomy for bleeding immediately after a primary cardiac procedure has been shown to increase postoperative morbidity and mortality significantly [15, 16, 19]. Unsworth-White and associates [15] noted that resternotomy for bleeding after cardiac surgery was a significant predictor of prolonged intensive care unit stay, need for intraaortic balloon pump insertion, and death. Dacey and associates [20] reported risk factors for hemorrhage in a multivariate analysis of 8,586 patients in a retrospective study from the Northern New England Cardiovascular Disease Study Group, noting that older age, smaller body surface area, prolonged cardiopulmonary bypass, and number of distal anastomoses were associated with increased bleeding risks. In these patients, in-hospital mortality was nearly three times higher and the average length of stay from surgery to discharge was significantly longer. High rates of reexploration for hemorrhage were observed in patients with prolonged (> 150 minutes) cardiopulmonary bypass and in those requiring an intraaortic balloon pump intraoperatively. The use of thrombolytic therapy within 48 hours of surgery was associated, but not significantly, with the need for reexploration [20].
In a study examining reexploration for bleeding, morbidity, and mortality in 6,100 patients after cardiac surgery, Moulton and coworkers [16] analyzed preoperative and intraoperative risk factors associated with reexploration and modeled reexploration itself as an independent risk factor for adverse outcomes along with patient and operative variables. In their model, reexploration for bleeding was noted to be an independent multivariate predictor of operative death, postoperative renal failure, adult respiratory distress syndrome, prolonged mechanical ventilation, sepsis, and atrial arrhythmias. When these outcomes were stratified by the amount of bleeding and reexploration versus observation, the authors noted that as the amount of bleeding increased, reexploration did not affect outcome. Further, in a multivariate stepwise logistic regression analysis of patients without risk factors for reexploration (< 70 years of age, in New York Heart Association class I, and undergoing elective CABG; n = 2,244), reexploration remained a strong multivariate risk factor for operative death, renal failure, adult respiratory distress syndrome, and atrial arrhythmias [16]. The observation that both early reexploration and excessive bleeding (with or without reexploration) affect morbidity and mortality after cardiac surgery suggests that the increased frequency of these events reported in abciximab-treated patients undergoing emergent CABG may place these patients at high risk for postoperative morbidity and mortality.
Risk factors for postoperative bleeding
The incidence of resternotomy for bleeding varies from 2% to 6% in published series [15, 16]. Each of the two large retrospective studies examining reexploration for postoperative bleeding in the cardiac surgical patient identified several common risk factors, including advanced age, preoperative renal dysfunction, and operation/reoperation other than CABG [15, 16]. Additional risk factors for transfusion requirement, and therefore increased morbidity and mortality, include emergent operation, postoperative coagulopathy, and prolonged bypass time [20, 26]. These risk factors define high-risk patient groups that are increasingly prevalent in both primary and secondary surgical intervention populations. Moreover, expanded indications for percutaneous intervention with GP IIb/IIIa agents will likely expand this subset of patients in the next 10 years.
Previous experience with antiplatelet agents varies. There are conflicting reports regarding incremental increases in postoperative bleeding with antiplatelet agents and thrombolytic therapy. Several studies have noted increased postoperative bleeding with these agents, but the larger published studies have not identified heparin, aspirin, or thrombolytic therapy as independent predictors of bleeding or reoperation [16]. Whether the newer, more potent and selective agents will independently increase risk is not yet known.
Transfusion: impact on outcome
Increasing transfusion requirement in postoperative CABG patients results in increased morbidity and mortality [26]. Van de Watering and coworkers [26] examined the effect of leukocyte depletion of transfused blood on complications and mortality in 914 cardiac surgical patients receiving at least one blood transfusion (fresh or stored, filtered, and packed cells without buffy coat), noting that the number of blood transfusions in all groups had a significant impact on morbidity and mortality. Transfusing more than 3 units of blood was associated with increased infection in all groups. Further, the number of blood transfusions received was directly related to postoperative mortality (Fig 2). Using multivariate logistic regression, the number of blood transfusions was the most important risk factor for postoperative mortality in all groups. If these data are extrapolated to the abciximab-treated patients undergoing emergent CABG, even mild bleeding confers significant risk for postoperative transfusion-associated morbidity.
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Fig 2. Effect of blood transfusion on mortality in CABG. (Adapted with permission from van de Watering and associates [26].)
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Blood product exposure, donor exposure
Concerns over transfusion of blood products include the risk of viral infection, use of limited blood resources, and cost. With current screening techniques, the risk of contracting the human immunodeficiency virus (HIV) has been estimated to be between 1 in 450,000 and 1 in 660,000 [27], approximately 1 in 80,000 for hepatitis C [28], and 1 in 200,000 for hepatitis B [29]. Despite heightened awareness of these complications and the adoption of aggressive blood-conserving strategies, 50% to 60% of patients undergoing coronary bypass surgery receive at least one blood product before discharge [26, 30–32]. Emergent and urgent CABG are associated with even higher rates of transfusion [33, 34]. Further, antiplatelet agents, such as aspirin, given before CABG, have previously been shown to increase operative blood loss and transfusion requirements [35, 36], yet they do not represent independent risk factors for resternotomy [16].
Transfusion rates for the published surgical experience in abciximab-treated patients are summarized in Table 1. Though these studies report substantial bleeding and transfusion rates, these rates fall within the wide variability of transfusions seen in both the elective and emergent cardiac surgical settings previously reported [26, 31, 34, 35]. Thus, whether increased use of abciximab in patients requiring emergency surgery will result in increased exposure to viral infection for the individual, while potentially decreasing the absolute number of transfusions and demand on blood bank resources, is not clear at this time.
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Cost of postoperative bleeding
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Bleeding and reexploration are markers for costly complications and significantly increase hospital resource use. Alvarez and associates [18, 19] described an early series of three patients who required emergency coronary bypass grafting for unsuccessful PTCA; they were pretreated with abciximab and had major postoperative hemorrhage, exposing these patients to 131 donors at a cost of $23,500 (Australian) for blood transfusion alone [18, 19]. This trend is also seen in the overall CABG patient population. In a review of 1,033 consecutive coronary bypass procedures performed at Duke University Medical Center during 1997, 22 patients underwent resternotomy for bleeding. In this group, complications such as cardiac arrest, ventricular arrhythmia, pulmonary edema, stroke, and renal failure were significantly increased compared with patients who did not require resternotomy. The average number of complications was 2.5 per patient with reexploration versus 0.5 per patient not reexplored. The average charge per day was significantly higher, while total charges were almost double for the resternotomy patients (Fig 3). Any abciximab-associated coagulopathy could therefore increase the average complication rate compared with nonbleeding patients, a trend seen only sporadically in the published series.
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Fig 3. Comparison of cost (charges) in reoperation for bleeding versus nonreoperative patients undergoing CABG (Duke University, unpublished data, 1997).
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Timing of surgery relative to abciximab treatment
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To minimize the real and perceived bleeding effects of abciximab, several measures have been suggested. Gammie and associates [13] suggested delaying surgical intervention in the failed PTCA/PTCS patient after observing excessive hemorrhage in abciximab-treated patients operated on within 12 hours of dosing, compared with nearly normal postoperative bleeding in patients operated on greater than 12 hours after abciximab. Other series have indirectly supported this observation. In the EPIC trial, the GP IIb/IIIa-treated patients (combined bolus/bolus plus infusion) were exposed to regional transfusions to a significantly greater extent despite an additional day in median time to CABG [10, 13]. However, delay must be considered within the context of the stability of the patient and the need to reestablish blood flow with definitive therapy.
Ironically, these agents may provide a safety factor in delay by stabilizing blood flow and "downgrading" previously emergent situations to urgent situations. The exact risk of early versus later surgical intervention in the abciximab-treated patient has not been tested prospectively. The competing incremental risks of excessive bleeding in early intervention in the presence of other risk factors for bleeding, such as renal failure, advanced age, and operation other than CABG, must be balanced against the timely need for revascularization and preservation of myocardium.
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The role of platelet transfusion
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The initial report of the EPIC trial noted that approximately 3% of the abciximab-treated patients required emergency surgery and 80% received platelets during the immediate perioperative period [1]. Subsequent reports noted excessive postoperative bleeding in abciximab-treated patients undergoing immediate emergency CABG who had been treated with platelet transfusion and procoagulant agents [1, 10, 15, 16, 37]. These reports led several authors to recommend routine platelet transfusion either en route, during, or immediately after CPB [37, 38]. Previous data on routine platelet infusion for CABG are conflicting. Del Rossi and coworkers [39] demonstrated a reduction in postoperative blood loss in patients receiving autologous platelet transfusions, whereas Simon and associates [40] noted no difference in blood loss associated with routine platelet transfusions post-CPB. In neither report, however, were patients exposed to antiplatelet agents such as aspirin or abciximab. Juergens and coworkers reported minimal or no transfusion requirements (two of four patients with 2 units and 4 units, respectively) with routine post-CPB platelet transfusion [38]. Kereiakes also suggested routine platelet transfusion in abciximab-treated patients, as well as judicious titration of heparin to target activated clotting time (ACT) levels to avoid excessive blood loss in emergency CABG [37]. Alvarez and associates reported major blood loss and transfusion requirements initially in a single patient and subsequently in two patients undergoing emergency CABG, despite platelet and aprotinin infusions [18, 19].
In a later series of 11 patients, Gammie and associates noted excessive bleeding in direct relation to the timing of surgery. In comparison with patients operated on 12 or more hours after abciximab treatment, patients operated on within 12 hours had significantly higher blood loss and required significantly more postoperative red blood cell and platelet transfusions [13]. These authors suggested delaying operation until platelet function has normalized, employing platelet transfusion in patients in whom delay is not possible, and modifying heparin management during CPB [13].
Later reports have not noted increased bleeding when incorporating these modifications, in addition to early platelet transfusion as necessary, in coagulation management of abciximab-treated patients [14].
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Abciximab removal and reversal
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No current method of reversal exists for GP IIb/IIIa agents. Manufacturer guidelines suggest platelet transfusion to bind free drug in the plasma. Although platelet transfusion remains the mainstay for treatment of diffuse bleeding in the abciximab-treated cardiac surgical patient, other novel approaches to drug elimination have been reported [41]. The use of a hemoconcentrator during cardiopulmonary bypass in an ex vivo perfusion model has been described to reduce plasma levels of abciximab, allowing transfused platelets to remain functional instead of absorbing available abciximab. This method of abciximab elimination could reduce platelet transfusion in the cardiac surgical patient and potentially could be modified for use in the percutaneous intervention patient with bleeding complications [41]. Further experience with this and other novel approaches may ultimately reduce or eliminate the excess transfusion requirements that have characterized these patients to date.
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Heparinization for cardiopulmonary bypass in the abciximab-treated patient
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Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand’s factor, and other adhesive molecules to GP IIb/IIIa receptor sites on activated platelets [42–44], causing decreased factor V release and inhibiting both fibrin deposition and thrombin generation. The clinical ramifications of these effects during CPB remain largely undefined, and no test of platelet function has correlated with hemorrhagic risk in this setting [44].
The ACT is prolonged in abciximab-treated patients, but the implications for clinical anticoagulation during percutaneous and surgical revascularization are unclear [13, 45]. Initial reports of excessive bleeding complications with empiric heparinization in abciximab-treated patients during both percutaneous revascularization and subsequent CPB in patients requiring emergent CABG [10–12] have led to reduced heparin anticoagulation during both percutaneous coronary revascularization and CABG, with reduction in bleeding risk predominantly in percutaneous intervention patients [6, 13, 14]. This reduction in hemorrhagic complications associated with decreased heparin dosing during percutaneous interventions may be related to poor bleeding control at the "surgical site." To date, there is no evidence that heparin dosing is related to postoperative hemorrhage in abciximab-treated CABG patients.
The monitoring of anticoagulation remains problematic in the abciximab-treated patient undergoing emergent CPB. Though the antiplatelet effects described previously are established, the prolongation of the ACT with smaller doses of heparin represents a dilemma for the cardiac surgeon. Increased hemorrhagic complications are associated with full-dose heparin in both percutaneous and operative revascularization, likely because of a heparin-abciximab interactive effect [43, 44], but reduced heparin dosage may place the patient at risk for prothrombotic events during CPB. Several platelet-monitoring assays are currently under development and testing. Assays such as the Platelet Function Analyzer (Dade-Behring, Deerfield, IL), the D3 anti-LIBS monoclonal antibody [46], and modifications of current assays such as the modified thromboelastographic method [44] may have a role in monitoring GP IIb/IIIa inhibitors during CPB. This information, combined with the ACT, may allow a clearer evaluation of anticoagulation status in abciximab-treated patients to guide heparin dosing perioperatively.
Current recommendations are empirical, based on time since abciximab administration. With recent administration (< 12 hours), it has been recommended that the initial heparin bolus be a half-dose (150 U/kg) before CPB, with additional heparin to achieve a target ACT of between 400 and 500 seconds [14, 37]. For delayed operation (> 12 hours), standard full-dose heparin (300 U/kg) should be given, with titration for a target ACT of 400 to 500 seconds [46]. It has been argued that full-dose heparin, using a fixed-dose scheme, regardless of ACT or abciximab interval, is the most conservative regimen to avoid underanticoagulation. Surgeons should work closely with perfusionists and anesthesiologists on these issues. They should exercise care in extrapolating from heparinization schemes derived to minimize bleeding from nonoperative or percutaneous arterial sheath sites to adequate heparinzation for CPB.
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Role of abciximab in platelet preservation
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The finding that thrombocytopenia was diminished in the placebo group compared with the abciximab group in the EPIC trial [12] has led to speculation regarding the role of the platelet GP IIb/IIIa receptor in CPB-mediated platelet dysfunction. Although platelet dysfunction post-CPB is the result of the interaction between mechanical trauma, complement, foreign surface exposure, and activation by adenosine diphosphate (ADP) [46, 47], agents such as aprotinin have been shown to preserve platelet function during CPB [46–48]. Previous studies of GP IIb/IIIa inhibitors derived from snake venom have demonstrated decreased platelet loss during simulated CPB [48]. Thus, the apparent paradoxical finding of preserved platelet numbers with depressed platelet function has led to speculation about a role for abciximab and other potentially shorter-acting GP IIb/IIIa inhibitors alone or in combination with aprotinin for "platelet anesthesia" during CPB.
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Summary
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The therapeutic benefits of GP IIb/IIIa agents in unstable coronary syndromes include improved outcome during percutaneous intervention and a reduction in emergency CABG rates. These benefits are offset by increased post-CABG bleeding or blood product and donor exposure. Though these effects may increase the risk of CABG performed after PTCA failure, the overall risk may be diminished by substantial benefits to patients with unstable coronary syndromes, namely, reduced need for emergent CABG and prevention of early intervention for myocardial infarction and death.
Surgeons have historically learned to deal effectively with new agents and anticoagulation strategies to maximize the outcome benefit of pre- and intraoperative anticoagulation and minimize excess risk of bleeding morbidity and mortality. A summary of surgical considerations in abciximab-treated patients undergoing urgent cardiac surgery is presented in Table 2. When choosing surgical delay to minimize abciximab effect of excessive hemorrhage and transfusion, the surgeon must consider the potential for interval coronary thrombosis in the urgent coronary bypass patient.
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Fig 4. Impact of bleeding and reexploration on morbidity and outcome in patients undergoing CABG. (Adapted with permission from Moulton and associates [16].)
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To provide safe protocols for cardiopulmonary bypass, intraoperative anticoagulation should be modulated to factor in abciximab anticoagulation effects and heparin-abciximab interactions. Modulation of abciximab effects with a hemoconcentrator during CPB and platelet transfusion after CPB may be beneficial when instituted early in coagulopathic patients. Antiplatelet therapy should be reinstituted after the abciximab effect has diminished and operative bleeding is no longer relevant, but before platelet aggregation potentially threatens bypass graft survival. Finally, initial reports of major blood loss during emergency CABG procedures in abciximab-treated patients have been tempered over time by the lessons learned in the effective management of post-CPB procoagulant therapy.
GP IIb/IIIa receptor antagonists represent an opportunity in the therapy of unstable coronary syndromes, as well as a challenge in postoperative hemostasis that, with careful surgical care, can maintain and improve beneficial outcomes. (Fig. 4)
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References
|
|---|
-
EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high risk coronary angioplasty. N Engl J Med 1994;330:956-961.[Abstract/Free Full Text]
-
Lefkovits J., Ivanhoe R.J., Califf R.M., et al. Effects of platelet glycoprotein IIb/IIIa receptor blockade by a chimeric monoclonal antibody (abciximab) on acute and six-month outcomes after percutaneous transluminal coronary angioplasty for acute myocardial infarction. EPIC investigators. Am J Cardiol 1996;77:1045-1051.[Medline]
-
Topol E.J., Ferguson J.J., Weisman H.F., et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of platelet IIb/IIIa inhibition for prevention of ischemic complication. JAMA 1997;278:479-484.[Abstract/Free Full Text]
-
EPISTENT Investigators. Enhancement of the safety of coronary stenting with the use of abciximab, a platelet glycoprotein IIb/IIIa inhibitor. Lancet 1998;352:87-92.[Medline]
-
Capture Study. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina. Lancet 1997;349:1429-1435 [Erratum, Lancet 1997;350:744.].[Medline]
-
EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997;336:1689-1696.[Abstract/Free Full Text]
-
Holmes D.R., Jr Preventing coronary restenosis and complications. N Engl J Med 1997;336:1748-1749.
-
Zaacks S.M., Liebson P.R., Calvin J.E., Parrillo J.E., Klein L.W. Unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol 1999;33:107-118.[Abstract/Free Full Text]
-
Casserly I.P., Hasdai D., Berger P.B., Holmes D.R., Jr, Schwartz R.S., Bell M.R. Usefulness of abciximab for treatment of early coronary artery stent thrombosis. Am J Cardiol 1998;82:981-985.[Medline]
-
Aguirre F.V., Topol E.J., Ferguson J.J., et al. Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. EPIC Investigators. Circulation 1995;91:2882-2890.[Abstract/Free Full Text]
-
Boehrer J.D., Kereiakes D.J., Navetta F.I., Califf R.M., Topol E.J. Effects of profound platelet inhibition with c7E3 before coronary angioplasty on complications of coronary bypass surgery. Am J Cardiol 1994;74:1166-1170.[Medline]
-
Blankenship J.C., Hellkamp A.S., Aguirre F.V., Demko S.L., Topol E.J., Califf R.M. Vascular access site complications after percutaneous coronary intervention with abciximab in the Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) trial. EPIC investigators. Am J Cardiol 1998;81:36-40.[Medline]
-
Gammie J.S., Zenati M., Kormos R.L., et al. Abciximab and excessive bleeding in patients undergoing emergency cardiac operations. Ann Thorac Surg 1998;65:465-469.[Abstract/Free Full Text]
-
Booth J.E., Patek V.B., Balog C., et al. Is bleeding risk increased in patients undergoing urgent coronary artery bypass surgery following abciximab [Abstract]?. Circulation 1998;98(Suppl):845.[Abstract/Free Full Text]
-
Unsworth-White M.J., Herriot A., Valencia O., et al. Resternotomy for bleeding after cardiac operation. Ann Thorac Surg 1995;59:664-667.[Abstract/Free Full Text]
-
Moulton M.J., Creswell L.L., Mackey M.E., Cox J.L., Rosenbloom M. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg 1996;111:1037-1046.[Abstract/Free Full Text]
-
Topol E.J., Lincoff A.M., Sapp S. Coronary stenting and use of abciximab. Lancet 1998;352:1311-1312.[Medline]
-
Alvarez J. Emergency coronary bypass grafting for failed percutaneous coronary artery stenting. J Thorac Cardiovasc Surg 1998;115:472-473.[Free Full Text]
-
Alvarez J.M., Harper R.W., Peverill R.E. Emergency coronary artery bypass grafting (CABG) after failed coronary artery intervention. Aust N Z J Med 1998;28:463-464.[Medline]
-
Dacey L.J., Munoz J.J., Baribeau Y.R., et al. Reexploration for hemorrhage following coronary artery bypass grafting. Arch Surg 1998;133:442-447.[Abstract/Free Full Text]
-
Keck S., Anderson C., Rieth J., Ford P., Stetler C. Cardiac tamponade. Heart Lung 1983;12:505-509.[Medline]
-
Weitzman L.B., Tinker W.P., Kronzon I., Cohen M.L., Glassman E., Spencer F.C. The incidence and natural history of pericardial effusion after cardiac surgery. Circulation 1984;69:506-511.[Abstract/Free Full Text]
-
Ikaheimo M.J., Huikuri H.V., Airaksinen K.E., et al. Pericardial effusion after cardiac surgery. Am Heart J 1988;116(Pt 1):97-102.[Medline]
-
Malouf J.F., Alam S., Gharzeddine W., Stefadouros M.A. The role of anticoagulation in the development of pericardial effusion and late tamponade after cardiac surgery. Eur Heart J 1993;14:1451-1457.[Abstract/Free Full Text]
-
Merrill W., Donahoo J.S., Brawley R.K., Taylor D. Late cardiac tamponade. J Thorac Cardiovasc Surg 1976;72:929-932.[Abstract]
-
Van de Watering L.M., Hermans J., Houbiers J.G., et al. Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery. Circulation 1998;97:562-568.[Abstract/Free Full Text]
-
Lackritz E.M., Satten G.A., Aberle-Grasse J., et al. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med 1995;333:1721-1725.[Abstract/Free Full Text]
-
Busch M.P., Korelitz J.J., Kleinman S.H., Lee S.R., AuBuchon J.P., Schreiber G.B., Retrovirus Epidemiology Donor Study. Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. Transfusion 1995;35:903-910.[Medline]
-
Centers for Disease Control and Prevention. Public Health Service interagency guidelines for screening donors of blood, plasma, organs, tissues and semen for evidence of hepatitis B and hepatitis C. MMRW Morb Mortal Wkly Rep 1991;40(RR-4):1-17.[Medline]
-
Surgenor D.M., Churchill E.L., Rizzo W.R.J., et al. Determinants of red cell, platelet, plasma and cryoprecipitate transfusions during coronary artery bypass graft surgery. Transfusion 1996;36:521-532.[Medline]
-
Magovern J.A., Sakert T., Benckart D.H., et al. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg 1996;61:27-32.[Abstract/Free Full Text]
-
Kochamba G.S., Pfeffer T.A., Sintek C.F., Khonsari S. Intraoperative autotransfusion reduces blood loss after cardiopulmonary bypass. Ann Thorac Surg 1996;61:900-903.[Abstract/Free Full Text]
-
Parsonnet V., Fisch D., Gielchinsky I., et al. Emergency operation after failed angioplasty. J Thorac Cardiovasc Surg 1988;96:198-203.[Abstract]
-
Brahos G.J., Baker N.H., Ewy H.G., et al. Aortocoronary bypass following unsuccessful PTCA. Ann Thorac Surg 1985;40:7-10.[Abstract]
-
Ferraris V.A., Ferraris S.P., Lough F.C., Berry W.R. Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting. Ann Thorac Surg 1995;59:1036-1037.[Free Full Text]
-
Goldman S., Copeland J., Moritz T., et al. Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy. Circulation 1988;77:1324-1332.[Abstract/Free Full Text]
-
Kereiakes D.J. Prophylactic platelet transfusion in abciximab-treated patients requiring emergency coronary bypass surgery [Letter]. Am J Cardiol 1998;81:373.[Medline]
-
Juergens C.P., Yeung A.C., Oesterle S.N. Routine platelet transfusion in patients undergoing emergency coronary bypass surgery after receiving abciximab. Am J Cardiol 1997;80:74-75.[Medline]
-
Del Rossi A.J., Cernaianu A.C., Vertrees R.A., et al. Platelet rich plasma reduces postoperative blood loss after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;100:281-286.[Abstract]
-
Simon T.L., Akl B.F., Murphy W. Controlled trial of routine administration of platelet concentrates in cardiopulmonary bypass surgery. Ann Thorac Surg 1984;37:359-364.[Abstract]
-
Poullis M., Manning R., Haskard D., Taylor K. Reopro removal during cardiopulmonary bypass using a hemoconcentrator. J Thorac Cardiovasc Surg 1999;117:1032-1034.[Free Full Text]
-
Reverter J.C., Beguin S., Kessels H., Kumar R., Hemker H.C., Coller B.S. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis.". J Clin Invest 1996;98:863-874.[Medline]
-
Lefkovits J., Plow E.F., Topol E.J. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995;332:1553-1559.[Free Full Text]
-
Greilich P.E., Alving B.M., O’Neill K.L., Chang A.S., Reid T.J. A modified thromboelastographic method for monitoring c7E3 Fab in heparinized patients. Anesth Analg 1997;84:31-38.[Abstract]
-
Theroux P. Oral inhibitors of platelet membrane receptor glycoprotein IIb/IIIa in clinical cardiology. Am Heart J 1998;135(Suppl, Pt 2):107-112.[Medline]
-
Weerasinghe A., Taylor K.M. The platelet in cardiopulmonary bypass. Ann Thorac Surg 1998;66:2145-2152.[Abstract/Free Full Text]
-
Lavee J., Raviv Z., Smolinsky A., et al. Platelet protection by low-dose aprotinin in cardiopulmonary bypass. Ann Thorac Surg 1993;55:114-119.[Abstract]
-
Musial J., Niewiarowski S., Rucinski B., et al. Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms. Circulation 1990;82:261-273.[Abstract/Free Full Text]
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Abstract
Introduction
