The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery.
BACKGROUND
Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery.


METHODS
Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used.


RESULTS
Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti-thrombin III complexes 33.7 +/- 3.6, 53.6 +/- 7.0 and 44.2 +/- 5.3 microg/l 2 h after CPB and F1 + 2 fragment 1.50 +/- 0.10, 2.37 +/- 0.37 and 2.04 +/- 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti-fibrinolytic drugs (D-dimers 0.427 +/- 0.032, 0.394 +/- 0.039 and 2.808 +/- 0.037 mg/l 2 h after CPB, respectively). The generation of d-dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti-plasmin complexes 0.884 +/- 0.095, 2.764 +/- 0.254 and 1.574 +/- 0.185 mg/l 2 h after CPB, respectively).


CONCLUSIONS
Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery.
Kuitunen
A
A
Department of Anesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland. anne.kuitunen@hus.fi
Hiippala
S
S
Vahtera
E
E
Rasi
V
V
Salmenperä
M
M
D000368:Aged; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis*; D014148:Tranexamic Acid / Q000494:pharmacology*
D000933:Antifibrinolytic Agents; D006454:Hemoglobins; D006490:Hemostatics; D011486:Protein C; D017293:Protein S; D014148:Tranexamic Acid; D007611:Aprotinin; D013917:Thrombin