ACTIVATED CLOTTING TIME, ANTICOAGULATION, USE OF HEPARIN, AND THROMBIN ACTIVATION DURING EXTRACORPOREAL-CIRCULATION - CHANGES UNDER APROTININ THERAPY

In a prospective randomized double-blind study, the activated clotting time (ACT), heparin use, parameters of anticoagulation, and thrombin activation during extracorporeal circulation were studied in 20 patients who underwent aortocoronary bypass operations. The patients were divided into two groups: Group A was given a placebo, while Group B was given aprotinin according to the high-dosage Trasylol(R) scheme. During ACT-controlled heparinization (ACT > 460 s) there was a significant heparin reduction in Group B (22 100 USP-E) in comparison to Group A (35 200 USP-E). Despite this lower quantity of total heparin, the ACT in Group B was significantly extended (Group B = 837 s, Group A = 492 s). The ACT did not correlate thereby with the heparin concentration or the total quantity of heparin in either group. In contrast to the control group, there was no increased thrombin generation in the aprotinin group. The thrombin-antithrombin III complexes (Group A = 143 mug/L, Group B = 102 mug/L) as well as the specific dimers (Group A = 2755 ng/ml, Group B = 448 ng/ml) were significantly lower under the use of aprotinin. The connection between the ACT, the heparin concentration, and the aprotinin concentration was further investigated in an ex-vivo model. The ACT samples were diluted with the aim of eliminating the influence of aprotinin. Under these conditions it was shown that for heparin concentrations between 2-4 U/ml there was a parallel shift of the ACT/heparinconcentration curve with the addition of aprotinin in a defined concentration range of 200-300 KIU. In the framework of a further clinical study, normal ACT values and those in diluted ACT samples (physiological NaCl solution 1:1) were determined in patients who had undergone aortocoronary bypass operations under aprotinin therapy. The ACT values of the diluted samples remained in normal ranges, in contrast to those of the undiluted samples: The early extreme peak of the curves did not occur, but after a steep increase a plateau was reached. This was identical to the distribution kinetics of the heparin. Aprotinin significantly inhibits thrombin generation, which is increased during ECC despite heparinization. At the same time, decreased use of heparin was facilitated without leading either clinically or chemically to an increased clotting tendency. On the basis of the lack of correlation of the ACT under aprotinin therapy, the antagonization of heparin can be related only to the total quantity of heparin given. The experimental approach of washing out the aprotinin influences by diluting the ACT samples appears to be useful.