Comparison of the effects of tranexamic acid, aprotinin and placebo on blood conservation, fibrinolysis and platelet function with extensive heart surgery

Introduction

CPB results in fibrinolysis as reflected by increased plasmin concentrations and fibrin degradation products, both of which have deleterious effects on platelet function. We designed a study to compare the effects of a high dose of aprotinin (A), tranexamic acid (TA) and no treatment (P) on blood loss, transfusion of blood products, fibrinolysis and platelet function during and after heart surgery.

Methods

After IRB approval, 60 consecutive consenting patients undergoing combined aortic valve replacement surgery with CABG were studied. They were randomized to either: high-dose A (280 mg loading dose, 70 mg/hour infusion rate and 280 mg in the prime) (n = 20), TA (100 mg/kg loading dose, 1 mg/kg/hour infusion rate) (n = 20), or saline (n = 20). The effect of A and TA on some markers for the activation of thrombin formation and fibrinolysis was studied (D-dimer, plasminogen, α₂-anti-plasmin,antithrombin and glycocalicin, a fragment of the platelet-membrane GPIb). Sampling was at induction (t1), at the start and end of CPB (t2, t3), and at 1, 4 and 24 hours after CPB (t4, t5, t6). ANOVA for repeated measurements was applied for statistical comparisons between groups. P < 0.05 was considered significant. Data are expressed as mean values ± SEM.

Results

Study groups did not differ with regard to demographic data and type of operation. Blood loss and chest tube drainage was significantly less in the A and TA groups as compared with the P group at all time points and was accompanied with the use of less blood products, volume replacement and higher hemoglobin levels. The duration of the surgical post-CPB period was significantly shorter in the A and TA groups (55 ± 18, 71 ± 19 and 84 ± 26 min, respectively). There was no difference in platelet count between groups. There were no re-explorations for postoperative bleeding. Inhibition of fibrinolysis was significant with both antifibrinolytic drugs (D-dimers 578 ± 81, 550 ± 105 and 3603 ± 440 μg/ml at t4). During and after the operation, the D-dimers were much higher in the placebo group. α₂-antiplasmin levels were higher in the A group compared with the TA and P groups. This effect was present until 24 hours after CPB. TA had no effect on this parameter. Plasminogen levels were lower in the TA group at t4, t5 and t6. TA patients more often received additional boluses of heparin to maintain ACT > 480 s during bypass (15/20 patients versus 9/20 and 8/20 patients in the A and P groups, respectively). aPTT values were significantly prolonged at the end of CPB in the A group. Antithrombin values were significantly higher in the A group at t3, t4 and t5. Glycocalicin values were slightly higher in the TA group during bypass.

Discussion

TA can inhibit fibrinolytic activity by blocking plasmin(ogen) activity measured as the D-dimer level, but seems to have no influence on neutralization of plasmin by α₂-antiplasmin. Both A and TA effectively suppress the appearance of markers of fibrinolysis as compared with placebo. The results also suggest that the antifibrinolytic effects of TA and A can reduce blood loss in patients undergoing extensive CPB surgery.