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J Thorac Cardiovasc Surg 2007;134:1069-1070
© 2007 The American Association for Thoracic Surgery

Brief Communication

Fatal intraoperative thrombosis in contemporary adult thoracic aortic surgery requiring deep hypothermic circulatory arrest: Observations from the literature, 1993–2006

Cardiothoracic Section, Anesthesiology and Critical Care, Philadelphia, Pa.

Received for publication May 22, 2007; accepted for publication May 30, 2007.

^_* Address for reprints: John G. T. Augoustides, MD, FASE, Cardiothoracic Section, Anesthesiology and Critical Care, Dulles 680, HUP, 3400 Spruce St, Philadelphia, PA 19104-4283. (Email: yiandoc{at}hotmail.com).

Fatal intravascular coagulation in the setting of thoracic aortic surgery with deep hypothermic circulatory arrest (DHCA) was highlighted in a case series (n = 20) that identified exposure to aprotinin as a significant risk factor.¹ The findings in this case series have since been attributed to inadequate heparinization because it was only appreciated thereafter that aprotinin prolongs the celite-based activated clotting time (ACT).² However, even in the presence of adequate heparinization by kaolin-based ACT or heparin concentration, case reports of fatal thrombosis in thoracic aortic surgery with DHCA have persisted (n = 5, 1998–2006).^2–5 The purpose of this brief communication is to review this case series as a platform from which further research can be planned. The literature search was conducted with PubMed (last entry: May 21, 2007) with the following search terms: thrombosis and DHCA; aprotinin and thrombosis in DHCA; aminocaproic acid and thrombosis in DHCA; and tranexamic acid and thrombosis in DHCA.

As a group, the published case reports of adult DHCA thrombosis can be summarized as follows^2–5:

1 The 5 patients were all older than 60 years (2 men and 3 women).

2 All underwent thoracic aortic procedures with DHCA.

3 Factor V Leiden was identified in 2 of the 5 patients.^4,5

4 All patients had antifibrinolytic therapy (3 with aprotinin and 2 with aminocaproic acid).

5 Anticoagulation was titrated with heparin to maintain the ACT at longer than 500 seconds, the heparin concentration at greater than 2.7 U/mL, or both. The kaolin-based ACT was always used in the presence of aprotinin.

6 Circulatory collapse caused by intravascular thrombosis began in all cases within 60 minutes of separation from cardiopulmonary bypass and protamine administration.

7 The circulatory collapse was life-threatening and resistant to pharmacologic support. In all cases it necessitated return to cardiopulmonary bypass.

8 The degree of thrombosis was massive, involving the heart chambers, thoracic aorta, pulmonary arteries, and great veins. In 4 of 5 patients, the disseminated thrombus was evident intraoperatively. In the fifth patient autopsy revealed extensive thrombosis within the small pulmonary arteries that was responsible for fatal intraoperative right ventricular failure.

9 The syndrome caused intraoperative death in all 5 patients.

Of course, this small case series has the usual inherent limitations. There are many more questions than answers. However, the following observations might serve to direct further investigation of this lethal syndrome to improve its management:

1 A worldwide case registry would allow a greater case number for further in-depth analysis.

2 Hypercoagulable states, such as Factor V Leiden, might have a role in the pathophysiology of this syndrome.

3 In the presence of an antifibrinolytic, standard-of-care anticoagulation with heparin for adult DHCA does not protect all patients against serious intraoperative thrombotic complications.

4 Aprotinin is not the only antifibrinolytic associated with this syndrome. To date, no cases of this syndrome have been reported in association with tranexamic acid.

5 When a case occurs, the following considerations might improve clinical care:

a Blood samples from the patient should be analyzed in consultation with a hematologist to identify possible mechanisms.

b The index patient and family should be screened for underlying hypercoagulable states.

c Patient autopsy might be required to determine the mechanism of death, especially if the thrombosis is not evident intraoperatively.

Despite the major advances in thoracic aortic surgery with DHCA, there are still major clinical challenges, including this thrombotic syndrome in the face of standard-of-care anticoagulation. Further collaborative research should advance our understanding and management of this thrombotic syndrome in the future.

References

1. Sundt TM, Kouchoukos NT, Saffitz JE, Murphy SF, Wareing TH, Stahl DJ. Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest. Ann Thorac Surg 1993;55:1418-1424.[Abstract/Free Full Text]
   
2. Alvarez JM, Goldstein J, Mezzatesta J, Flanagan B, Dodd M. Fatal intraoperative pulmonary thrombosis after graft replacement of an aneurysm of the arch and descending aorta in association with deep hypothermic circulatory arrest and aprotinin therapy. J Thorac Cardiovasc Surg 1998;115:723-724.[Free Full Text]
   
3. Augoustides JGT, Lin J, Gambone AJ, Cheung AT. Fatal thrombosis in an adult after thoracoabdominal aneurysm repair with aprotinin and deep hypothermic circulatory arrest. Anesthesiology 2005;103:215-216.[Medline]
   
4. Shore-Lesserson L, Reich DL. A case of severe diffuse venous thromboembolism associated with aprotinin and hypothermic circulatory arrest in a cardiac surgical patient with factor V Leiden. Anesthesiology 2006;105:219-221.[Medline]
   
5. Fanashawe MP, Shore-Lesserson L, Reich DL. Two cases of fatal thrombosis after aminocaproic acid therapy and deep hypothermic circulatory arrest. Anesthesiology 2001;95:1525-1527.[Medline]
   

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John G.T. Augoustides Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Augoustides, J. G.T. Search for Related Content PubMed Articles by Augoustides, J. G.T. Related Collections Cardiac - pharmacology Extracorporeal circulation Great vessels