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Anesthesiology:
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Is the Activated Clotting Time Dangerous?

Avidan, Michael S. M.B.B.Ch., D.A., F.C.A.(SA)*; Despotis, George J. M.D.

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In Reply:—

We thank Dr. Metz for his interest in our study and for his thought-provoking letter. We agree with the comments about the limitations of the activated clotting time (ACT) test and the lack of evidence supporting any particular approach linked to any particular target ACT number. However, the limitations of the ACT do not undermine the importance of heparin resistance (or decreased sensitivity to heparin), an entirely different problem. Dr. Metz suggests that “The alternative [treatment for heparin resistance] not discussed by Avidan et al. is to ensure that the heparin went intravascular . . . and then ignore the ACT.” This is potentially a risky approach, because with severe heparin resistance, there may be an apparent adequate blood heparin concentration without sufficient anticoagulant effect.
We cannot agree with the sentiment that “Heparin resistance is a disease carried in ACT tubes.” This statement implies that the diagnosis of heparin resistance owes its existence entirely to a flawed point of care coagulation test. Of course it is likely that, following the unreliability of the ACT, some false diagnoses of heparin resistance will be made, but to attribute all diagnoses of heparin resistance to the unreliability of the ACT is disingenuous. Heparin depends on the presence of antithrombin for its anticoagulant efficacy. Antithrombin deficiency and antithrombin abnormalities are important and very real causes of heparin resistance.1–3 In many of the patients in our study, we demonstrated low blood antithrombin concentrations both at baseline and during cardiopulmonary bypass.4 We can therefore state confidently that the diagnosis of heparin resistance in our patients rests on a more solid foundation than a potentially unreliable ACT number.
We do, however, agree that monitoring heparin concentration may be more effective than monitoring the ACT in guiding anticoagulation for cardiopulmonary bypass. Of course, clinicians would have to agree on the appropriate heparin concentration for all patients. This would vary according to each physician’s bias and of course each individual’s sensitivity to heparin.
Michael S. Avidan, M.B.B.Ch., D.A., F.C.A.(SA),*
George J. Despotis, M.D.
*Washington University School of Medicine, St. Louis, Missouri. avidanm@msnotes.wustl.edu
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References

1. Bauters A, Zawadzki C, Bura A, Thery C, Watel A, Subtil D, Aiach M, Emmerich J, Jude B: Homozygous variant of antithrombin with lack of affinity for heparin: Management of severe thrombotic complications associated with intrauterine fetal demise. Blood Coagul Fibrinolysis 1996; 7:705–10

2. Nielsen LE, Bell WR, Borkon AM, Neill CA: Extensive thrombus formation with heparin resistance during extracorporeal circulation: A new presentation of familial antithrombin III deficiency. Arch Intern Med 1987; 147:149–52

3. Chasse JF, Esnard F, Guitton JD, Mouray H, Perigois F, Fauconneau G, Gauthier F: An abnormal plasma antithrombin with no apparent affinity for heparin. Thromb Res 1984; 34:297–302

4. Avidan MS, Levy JH, Scholz J, Delphin E, Rosseel PMJ, Howie MB, Gratz I, Bush CR, Skubas N, Aldea GS, Licina M, Bonfiglio LJ, Kajdasz DK, Ott E, Despotis GJ: A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass. Anesthesiology 2005; 102:276–84

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