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J Thorac Cardiovasc Surg 1996;112:537-538
© 1996 Mosby, Inc.

BRIEF COMMUNICATIONS

BRIEF COMMUNICATIONS
APROTININ AND AORTIC CANNULA THROMBOSIS

Dallas, Tex.

From the Departments of Cardiothoracic Surgery^a and Anesthesia,^b Baylor University Medical Center, Dallas, Tex.

Received for publication Sept. 26, 1995 Accepted for publication Oct. 20, 1995. Address for reprints: G. Kimble Jett, MD, 1151 N. Buckner Blvd., No. 205, Dallas, TX 75218.

Aprotinin has been advocated to reduce perioperative blood loss in patients undergoing cardiopulmonary bypass (CPB). ^1,2 Its effect on the coagulation cascade has been investigated by many researchers and its clinical effectiveness has been documented. ^3,4 However, the potential adverse sequelae of potent antifibrinolytic therapy has received less attention.

Thrombus formation has been reported with pulmonary artery catheters after aprotinin administration. ⁵ Thrombus formation in the aortic outflow cannula, reported herein, represents a unique complication of antifibrinolytic therapy and merits attention.

Case report

A 64-year-old woman weighing 78 kg, with end-stage congestive cardiomyopathy, underwent cardiac transplantation. Two million kallikrein inactivator units (KIU) of aprotinin was bolused intravenously before the initial skin incision, followed by a continuous infusion at 500,000 KIU/hr. Additionally, another 2 million KIU of aprotinin was added to the extracorporeal circuit as a priming dose before institution of CPB. Before CPB, heparin (4 mg/kg) was administered and an activated clotting time (ACT) of 600 seconds obtained. (ACT was measured in celite test tubes in an automated device [Hemochron, International Technidyne Corp., Edison, N.J.]. ACTs during CPB ranged between 600 and 963 seconds.) After implantation of an 18-year-old donor heart, the patient had cardiac graft dysfunction resulting in cardiogenic shock and hypotension. Mechanical support with intraaortic balloon counterpulsation and aggressive inotropic support were instituted. The patient was weaned from CPB and protamine was administered.

After decannulation and observation in the operating room for 4 hours, the patient's cardiac hemodynamics worsened. She was therefore reheparinized (4 mg/kg) and, with the aid of CPB, ABIOMED BVS 5000 (ABIOMED Cardiovascular, Inc., Danvers, Mass.) biventricular assist devices (BVADs) were inserted. A new extracorporeal circuit and new cannulas were used. Aprotinin was not rebolused or added to the prime of the new CPB circuit, but the continuous infusion was continued throughout the period of observation and insertion of BVADs. The CPB time required for BVAD insertion was 105 minutes. ACTs measured during the second CPB time ranged from 984 to 1199 seconds. After separation from CPB and institution of biventricular support, the patient had stable hemodynamics. The aortic cannula was left in place for approximately 50 minutes after cessation of CPB for volume administration. Heparin was reversed with protamine and the continuous infusion of aprotinin was continued. The pump sucker was discontinued immediately with cessation of CPB and start of protamine administration. On removal of the aortic cannula, thrombus was noted in the lumen of the outflow cannula, which extended through the purse-string suture into the aorta. The thrombus was extracted from the aorta before the purse-string suture was secured. The venous cannula removed earlier had no thrombus.

The patient's hemodynamic status stabilized with biventricular support after the operation. The next morning she had a dilated and fixed left pupil and was neurologically unresponsive. A computed tomographic scan revealed a large infarct in the left hemisphere with generalized cerebral edema and tentorial herniation. Hemodynamic support was withdrawn at this point at the family's request. After termination of support, no thrombus was noted in the BVADs.

Discussion

Aprotinin is a potent nonspecific protease inhibitor that exerts its antifibrinolytic effect by kallikrein inhibition, thereby hindering progression of the complement and coagulation cascades. It is further believed to preserve platelet function by its effect on glycoprotein IB, the platelet membrane receptor for von Willebrand factor. ^1,2 High-dose infusion of this agent initiated before complex cardiac operations has been shown to reduce intraoperative and postoperative blood loss. This effect appears to be independent of systemic heparinization. ^3,4 Aprotinin has not been shown to be prothrombotic.

Outflow cannula thrombus after administration of aprotinin has not been previously described. Although early thrombus formation was reported with pulmonary artery catheters after aprotinin administration, ⁵ there is a question of underheparinization in that report, because the ACT was only 497 seconds. Our patient had adequate anticoagulation. In addition, the pump sucker was immediately withdrawn from the field with protamine administration. New aortic and venous cannulas, as well as a new extracorporeal circuit, were used for BVAD insertion. We believe that leaving the aortic cannula for volume administration for a period of time after CPB contributed to stasis and thrombus formation within the aortic cannula. Earlier removal of the aortic cannula may have prevented this complication.

Thrombus formation, both microscopic and macroscopic, has the potential for disastrous complications in patients receiving antifibrinolytic therapy. The risk of thrombus formation may be increased with stasis of blood. We would therefore recommend early removal of intravascular catheters when antifibrinolytic therapy has been instituted.

References

1. Harder MP, Eijsman L, Roozendaal KJ, van Oeveren W, Wildevuur RH. Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass. Ann Thorac Surg 1991;51:936-41.[Abstract]
   
2. Havel M, Teufelsbauer H, Knöbl P, Dalmatiner R, Jaksch P, Zwölfer W, et al. Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation. J THORAC CARDIOVASC SURG 1991;101:968-72.[Abstract]
   
3. Hardy JF, Desroaches J. Review article: Natural and synthetic antifibrinolytics in cardiac surgery. Can J Anaesth 1992;39:353-65.[Medline]
   
4. Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin (Trasylol). J THORAC CARDIOVASC SURG 1989;97:364-72.[Abstract]
   
5. Bohrer H, Fleischer F, Lang J, Vahl C. Early thrombus formation on pulmonary artery catheters in cardiac surgical patients receiving high dose aprotinin. J Cardiothorac Anesth 1990;4:222-6.[Medline]
   

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This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Richard Gitter Peter Alivizatos Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gitter, R. Articles by Jett, G. K. Search for Related Content PubMed PubMed Citation Articles by Gitter, R. Articles by Jett, G. K.