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Correspondence  |   July 2005
Fatal Thrombosis in an Adult after Thoracoabdominal Aneurysm Repair with Aprotinin and Deep Hypothermic Circulatory Arrest
Author Affiliations & Notes
  • John G. T. Augoustides, M.D.
    *
  • * Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Article Information
Correspondence
Correspondence   |   July 2005
Fatal Thrombosis in an Adult after Thoracoabdominal Aneurysm Repair with Aprotinin and Deep Hypothermic Circulatory Arrest
Anesthesiology 7 2005, Vol.103, 215-216. doi:
Anesthesiology 7 2005, Vol.103, 215-216. doi:
To the Editor:—
We report a case of fatal aortic thrombosis after aprotinin exposure in an adult undergoing repair of a thoracoabdominal aneurysm using cardiopulmonary bypass and deep hypothermic circulatory arrest (DHCA).
A 78-yr-old woman presented with a ruptured thoracoabdominal aortic aneurysm involving the aortic arch (Crawford type I). The patient was taken emergently to the operating room for repair using our DHCA protocol that has been previously described.1–6 
Anesthetic induction was with titrated fentanyl and midazolam. Neuromuscular blockade was achieved and maintained with titrated pancuronium. The trachea was intubated with a left-sided double-lumen tube (Tyco Healthcare/Mallinckrodt, St. Louis, MO). Correct endotracheal position was confirmed by serial fiberoptic bronchoscopy. Intraoperative monitoring included American Society of Anesthesiologists routine monitors as well as indwelling radial arterial and pulmonary arterial catheters. Because of the emergent nature of the procedure, a lumbar cerebrospinal fluid drain was not placed. Anesthesia was maintained with isoflurane in oxygen, as well as titrated fentanyl and midazolam.
The patient was given aprotinin (Bayer Corporation, Pittsburgh, PA) as follows: 2 million kallikrein inhibitory units intravenously as a load, followed by an infusion of 0.5 million kallikrein inhibitory units per hour. The cardiopulmonary bypass crystalloid prime was also loaded with aprotinin (2 million kallikrein inhibitory units).
The patient was positioned in the right lateral decubitus position. Surgical incision, dissection, and initiation of cardiopulmonary bypass were uneventful. Heparinization for cardiopulmonary bypass was titrated to maintain the activated coagulation time (kaolin activator) of greater than 600 s. The surgical repair was technically uncomplicated; the aorta was replaced with a Hemashield vascular graft (Boston Scientific, Natick, MA). The cardiopulmonary bypass time was 212 min, with a deep hypothermic circulatory arrest time of 38 min.
After successful separation from cardiopulmonary bypass, protamine was administered in a titrated fashion without adverse reaction. Despite aprotinin and adequate protamine (calculated to neutralize the full dose of heparin), hemostasis in the surgical field was not achieved. There was significant microvascular bleeding. No overt vascular bleeding was detected despite careful surgical inspection. Platelet infusion was begun. Ten minutes after initiation of the platelet infusion, the patient experienced cardiac arrest that was refractory to pharmacologic resuscitation. Transesophageal echocardiography revealed diffuse intraaortic thrombosis (figs. 1 and 2). The patient did not respond to further resuscitative efforts. The family declined a postmortem examination.
Fig. 1. Short axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 1. Short axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 1. Short axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
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Fig. 2. Long axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 2. Long axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 2. Long axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
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Catastrophic thrombosis with aprotinin in DHCA was first noted in the early 1990s.7 The most likely explanation for these observations was inadequate heparinization because it was only appreciated in the mid-1990s that aprotinin exposure prolongs the activated clotting time.8 At our institution, we perform 70–80 thoracic aortic procedures with DHCA per year. Our DHCA protocol includes routine application of an antifibrinolytic, either aminocaproic acid or aprotinin. Aprotinin is reserved for the high-risk DHCA population.1–4 
Inadequate heparinization as the cause of the prothrombotic state in this case is extremely unlikely, given that our standard DHCA protocol was followed and given the DHCA experience at our institution. It is more likely that the prothrombotic state was multifactorial in etiology: disseminated intravascular coagulation triggered by hypothermic cardiopulmonary bypass, the antifibrinolytic action of aprotinin, neutralization of heparin, and the presence of transfused functional platelets. The presence of hemostatic aortic graft material in this case was Hemashield (Boston Scientific), which, although hemostatic, has not been associated with acute intravascular thrombosis.9,10 The mechanism of this fatal thoracic aortic thrombosis is unclear.
Fatal thrombosis has been reported in adult DHCA; the antifibrinolytic, however, was not aprotinin but aminocaproic acid.11 This syndrome has also been reported in pediatric cardiopulmonary bypass; the antifibrinolytic was aprotinin.12 
Therefore, our case is the first reported case of fatal thrombosis in an adult undergoing DHCA in the presence of aprotinin despite adequate heparinization. Despite adequate heparinization, this syndrome is still possible in cardiovascular surgery necessitating cardiopulmonary bypass, regardless of antifibrinolytic or patient age. Further hypothesis-driven perioperative research is required to understand and prevent this uncommon but important complication associated with antifibrinolytic therapy.
* Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
References
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Fig. 1. Short axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 1. Short axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 1. Short axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
×
Fig. 2. Long axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 2. Long axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
Fig. 2. Long axis view of descending aorta with transesophageal echocardiography, showing aortic graft lumen filled with thrombus. 
×