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Departments of
*Anesthesiology,
Pathology and ImmunologyWashington University School of Medicine, St. Louis, Missouri; and
Departments of Pathology and Internal MedicineSt. Louis University School of Medicine, St. Louis, Missouri
Address correspondence and reprint requests to George J. Despotis, Department of Anesthesiology, Washington University School of Medicine, Box 8054, 660 S. Euclid Ave., St. Louis, MO 63110.
Anticoagulation with recombinant hirudin (r-hirudin) (RefludanTM) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 µg/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r2 = 0.83) linear relationships between ACT values and r-hirudin concentrations (
4 µg/mL) were observed in specimens obtained before CPB. However, ACT values were markedly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, with ACT values generally exceeding the ACT’s detection limit (>999 s) at hirudin concentrations >2 µg/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration 4 µg/mL) in the post-CPB period (0.022 ± 0.004 µg · mL-1 · s-1) were similar (P = 0.47) to those (0.019 ± 0.004 µg · mL-1 · s-1) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r2 = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 µg/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB.
Implications: A modified activated clotting time test system that may be helpful inmonitoring hirudin anticoagulation in patients with heparin-inducedthrombocytopenia during cardiac surgery with cardiopulmonary bypass isdescribed.
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