Antithrombin substitution before extracorporeal circulation attenuates perioperative coagulation activation and might decrease postoperative troponin elevation: a report of preliminary data

Objectives

Antithrombin (AT) has been proven to have major impact on perioperative activation of the coagulation system. The aim of this prospective, controlled, single-blind clinical trial was to determine the impact of AT substitution on perioperative thrombin formation.

Methods

Forty male coronary artery bypass graft patients participated in the trial. Prior to skin incision, 30 patients received AT according to a formula targeted at 120% AT activity before extracorporeal circulation (ECC), plus an additional 1000 U (group A, n = 10), 2000 U (group B, n = 10) or 3000 U (group C, n = 10) of AT in order to compensate for increased consumption during ECC. Control patients did not receive any AT substitution (group D, n = 10). The following parameters were determined perioperatively and until the fifth postoperative day: AT levels, parameters of coagulation activation (prothrombin fragment F_1.2, thrombin–antithrombin complex, D-dimer), inflammation (IL-6) and myocardial perfusion (troponin). Statistical comparison between groups was performed using analysis of variance, followed by Fisher's PLSD (P < 0.05) after ECC.

Results

AT substitution resulted in a significant increase in AT during ECC and until the first postoperative day (POD1), followed by a steep decrease at days 2–5. AT substitution attenuated thrombin generation significantly, as indicated by decreased concentrations of prothrombin fragments F_1.2, thrombin–antithrombin complexes and D-dimer at the end of surgery. Troponin was significantly higher during the postoperative period in patients who did not receive AT substitution (Fig. 1).

Figure 1

Perioperative course of troponin. *P < 0.05, versus groups A, B and C.

Conclusions

A substantial decrease in AT must be taken into account not only during ECC but also in the early postoperative period, indicating major enhancement of coagulation activation. High-dose AT substitution attenuates coagulation activation significantly. Attenuation of hemostatic activation may reduce postoperative complications, as lower postoperative troponin levels may indicate in AT substituted patients.