Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood

Havel, Michael; F, Grabenwöger; Schneider, Johannes; Laufer, G; Wollenek, Gregor; Owen, Alyson N.; Simon, Paul; Teufelsbauer, H.; Wolner, Ernst

doi:10.1016/s0022-5223(94)70336-1

Cited by 105 publications

(15 citation statements)

References 7 publications

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“…However, many case reports have associated thrombosis and thromboembolism with antifibrinolytic administration during liver transplantation and open‐heart surgery 6–17. Conversely, studies performed to date do not substantiate this concern 18–22. The anticoagulant, as opposed to a procoagulant, effect of aprotinin has been demonstrated in patients undergoing liver transplantation 22.…”

Section: Discussionmentioning

confidence: 99%

Intravascular thrombosis and thromboembolism during liver transplantation: Antifibrinolytic therapy implicated?

2004

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T he routine use of the antifibrinolytic agent aprotinin has been advocated during liver transplantation following the successful outcome of a multicenter trial. 1 We describe a patient who during an orthotopic liver transplant, while being administered an infusion of aprotinin, developed extensive hyperacute venous and systemic thromboses and thromboemboli. The etiology and prevention of this catastrophic event are discussed. Case ReportThe patient was a 48-year-old man, 69 kg, 71 in., with endstage liver disease secondary to hepatitis C cirrhosis. He had a history of esophageal variceal bleeding, coagulopathy, and mild renal insufficiency. At the time of transplantation his serum creatinine was 1.6 mg/L, serum potassium was 5.0 mEq/L, and the intraoperative laboratory coagulation studies indicated evidence of coagulopathy and fibrinolysis (Table 1). Initial thrombelastograph (TEG) data demonstrated a normal clot formation with no evidence of coagulopathy or fibrinolysis.To prevent hyperfibrinolysis and reduce blood transfusion requirements, at induction of anesthesia a "regular dose" aprotinin infusion was started at 2ϫ10 6 kallikrein inhibiting units (KIU) as a loading dose given intravenously over 20 minutes followed by a continuous infusion of 0.5ϫ10 6 KIU/h as described by Porte et al. 1 The liver transplant surgery progressed uneventfully during explantation of the diseased liver. Venovenous bypass, without heparin, was utilized during the anhepatic phase with bypass flow rates recorded at 2-2.3 L/min during portal and femoral bypass and 1-1.5 L/min after portal bypass was discontinued. Reperfusion of the new graft was also uneventful. Venovenous bypass was discontinued after a total time of 97 minutes, and the blood contained in the circuit was transfused back into the patient. The bypass circuit, including the centrifugal pump head, was observed to be free of blood clot or any obvious fibrin deposit.Coagulation studies were performed at the start of surgery a second time when the patient was anhepatic, and again following reperfusion of the new graft (0, 75, and 135 minutes from the start of the procedure). All the results were compatible with a severe coagulopathy together with fibrinolysis (Table 1). TEG data, however, still demonstrated a normal coagulation pattern.Six minutes after reperfusion, the patient became hypotensive and bradycardic, and the right heart filling pressures rose acutely. The patient rapidly went into asystole and could not be resuscitated despite full therapy.Autopsy findings were significant for multiple arterial and venous hyperacute thromboses. Extensive bilateral pulmonary thromboemboli were found, together with intracardiac clot in the right atrium, right ventricle, and inferior vena cava. Much of this clot appeared fresh and certainly some of this clot appeared to be seeding around the pulmonary artery catheter. No septal defects were found in the heart, but thromboses were also noted in the aorta, the right and posterior descending coronaries, bilateral iliac, internal c...

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Section: Discussionmentioning

confidence: 99%

Intravascular thrombosis and thromboembolism during liver transplantation: Antifibrinolytic therapy implicated?

2004

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“…Aprotinin is the only agent examined in multiple studies. Three studies found no significant difference in the patency of grafted vessels when examined postoperatively 8‐10 . The effects of aprotinin on graft patency, MI, and blood loss in patients undergoing primary CABG with CPB were reported by Alderman and coworkers 7 .…”

Section: Aprotininmentioning

confidence: 86%

Hemostatic agents

Levy¹

2004

Transfusion

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“…6,12 The effects of aprotinin on graft patency have been described in 8 reports of randomized controlled trials. 7,[12][13][14][15][16][17][18] Only one showed a concerning trend to increased graft occlusion in the aprotinin group (8.0%) versus the placebo group (4.9%). Graft occlusion was not accompanied by an increase in the incidence of myocardial infarction in any study.…”

Section: Safetymentioning

confidence: 95%

Applications of Aprotinin in Cardiac Surgery

Levy

2004

Transfus Alt Transfus Med

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SUMMARY Aprotinin has been studied extensively in cardiac surgery and is the only FDA approved pharmacological treatment to reduce blood transfusion in coronary artery bypass grafting (CABG) associated with cardiopulmonary bypass (CPB). Aprotinin has been evaluated in multiple double blind, placebo‐controlled, multicenter studies in cardiac surgery. In US studies, aprotinin has not been associated with an increased risk of post‐CPB myocardial infarction, graft closure, or increased risk of renal dysfunction, and may in fact be associated with a decreased risk of stroke. The mechanism of action is complex, but aprotinin displays antiinflammatory properties due to its complex array of protease inhibition. As with any polypeptide, there is a risk of anaphylaxis that is influenced by prior exposure. Cardiac surgery can be associated with significant bleeding and the need for allogeneic blood products. Although multiple approaches have been reported to reduce bleeding and transfusions, aprotinin represents an important pharmacologic strategy to reduce bleeding.

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Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood

Cited by 105 publications

References 7 publications

Intravascular thrombosis and thromboembolism during liver transplantation: Antifibrinolytic therapy implicated?

Intravascular thrombosis and thromboembolism during liver transplantation: Antifibrinolytic therapy implicated?

Hemostatic agents

Applications of Aprotinin in Cardiac Surgery

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