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LETTER TO THE EDITOR

Aprotinin’s Effect on ACT is Not an Artifact

Director, Cardiac Anesthesia, Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, alerner{at}bidmc.harvard.edu

To the Editor:

In a recent editorial, Drs. Hogue and London (1) state "... that aprotinin could artifactually prolong the celite-based activated clotting time (ACT)."

While it is clear from numerous studies that aprotinin independently prolongs celite activated ACT (2,3), there is no reason to think that this effect is simply an artifact. Aprotinin, as a serine protease inhibitor and inhibitor of kallikrein, is an inhibitor of contact activation of the coagulation system (4). The prolongation of PTT by aprotinin that has also been demonstrated further demonstrates this effect (5). As suggested by Dietrich et al., (6) in the presence of aprotinin the celite ACT "is not ‘artificially’ prolonged," but, in fact, the kaolin ACT is "artificially shortened" by the binding of aprotinin to kaolin.

Aprotinin may also have heparin sparing effects during cardiopulmonary bypass (6). However, a small number of prospective studies (7) of thromboembolic complications that may or may not be related to aprotinin have suggested that clinicians, disregard the anticoagulant effect of aprotinin until further study of this issue is performed. Hunt et al. (8) suggested using this strategy by recommending a threshold of 750 s when using celite-based ACT in the presence of aprotinin. This number was not based on clinical study but rather the authors’ expert opinion that this represented an adequate heparin effect.

The "bottom line" is that aprotinin’s effect on celite-based ACT is real. What remains to be answered is the importance of this effect in vivo and how this effect interacts with aprotinin’s pro-hemostatic effects in individual patient situations.

REFERENCES

1. Hogue CW, London MJ. Aprotinin use during cardiac surgery: a new or continuing controversy? Anesth Analg 2006;103:1067–70.[Free Full Text]
2. Despotis GJ, Filos KS, Levine V, et al. Aprotinin prolongs activated and nonactivated whole blood clotting time and potentiates the effect of heparin in vitro. Anesth Analg 1996;82:1126–31.[Abstract]
3. Wang JS, Lin CY, Hung WT, et al. In vitro effects of aprotinin on activated clotting time measured with different activators. J Thorac Cardiovasc Surg 1992;104: 1135–40.[Abstract]
4. Despotis GJ, Joist JH. Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update. J Cardiothorac Vasc Anesth 13:18–29, 1999; discussion 36–7.
5. Despotis GJ, Alsoufiev A, Goodnough LT, et al. Aprotinin prolongs whole blood activated partial thromboplastin time but not whole blood prothrombin time in patients undergoing cardiac surgery. Anesth Analg 1995;81:919–24.[Abstract]
6. Dietrich W, Dilthey G, Spannagl M, et al. Influence of high-dose aprotinin on anticoagulation, heparin requirement, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open-heart surgery. A double- blind, placebo-controlled study. Anesthesiology 1995;83:679–89; discussion 29A–30A.[Web of Science][Medline]
7. Cosgrove DM, 3rd, Heric B, Lytle BW, et, al. Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. Ann Thorac Surg 54:1031–6, 1992; discussion 6–8.
8. Hunt BJ, Segal H, Yacoub M. Aprotinin and heparin monitoring during cardiopulmonary bypass. Circulation 1992;86:II410–2.[Medline]

This article has been cited by other articles:

				C. W. Hogue and M. J. London Aprotinin's Effect on ACT is Not an Artifact Anesth. Analg., May 1, 2007; 104(5): 1302 - 1303. [Full Text] [PDF]

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