POSTOPERATIVE HEMOSTASIS AND FIBRINOLYSIS IN PATIENTS UNDERGOING CARDIOPULMONARY BYPASS WITH OR WITHOUT APROTININ THERAPY

Intra- and postoperative blood loss during open heart surgery is reduc ed by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin admini stration on coagulation and fibrinolysis during and after cardiopulmon ary bypass (CPB). Thirty patients undergoing CPB M en randomly assigne d to two comparable groups for a double-blind study (16 patients recei ving high-dose aprotinin, 14 patients receiving placebo). Patients' pl asma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were me asured at regular intervals. In both groups, ATM level increased durin g surgery (from less than 30 to 90-110 ng/ml) and returned to normal 2 4 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CP B). The FbDP generated during surgery was greatly reduced in the aprot inin group (945 ng/ml) in comparison with the placebo group (1889 ng/m l, p = 0.004). After surgery, FbDP levels decreased in both groups wit h nadirs at 2nd day (placebo group. 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypofibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical man ner. This postoperative hypofibrinolysis is related to the changes of t-PA and PAI-1 levels: immediately after surgery there was a 2 fold in crease in t-PA level and a 4-5 fold increase in PAI-1 level in the two groups. During the following 24 h, t-PA levels decreased in both grou ps. In contrast, PAI-1 levels in the placebo group during the same tim e increased sharply to a maximum level (175.7 ng/ml). This further inc rease did not occur in the aprotinin group although it remained at a h igh level (79.2 ng/ml). The difference in the increase of PAI-1 betwee n the 2 groups (value at 24 h minus preoperative value: D1-T1) was sig nificantly different (p = 0.04). Then t-PA continued to decrease and P AI-1 began to decrease steadily. Total blood loss was significantly re duced by aprotinin therapy (3.06 ml/kg versus 5.86 ml/kg). The present study confirms the inhibitory effects of aprotinin on both fibrinolyt ic activity and blood coagulation activation during CPB, and reveals a n hypofibrinolytic period that lasts 48 h after surgery in both aproti nin and placebo groups. This inhibition of fibrinolysis is apparently associated with high PAI-1 level. The data of this study also show tha t 2 days after aprotinin therapy, there is no prolonged effect of apro tinin on fibrinolysis. In addition, the lower level of PAI-1 in the ap rotinin group after surgery might result from a protection of endothel ial cells by aprotinin, suggesting an unexpected benefit of aprotinin therapy.