Low doses of aprotinin in aortocoronary bypass surgery--advantages and disadvantages.
BACKGROUND
Excessive blood loss, as a result of augmented postoperative drainage, is considered one of the most serious cardiosurgical complications. The compounding constitutive anemia seems particularly harmful for patients with coronary artery disease. Aprotinin (Trasylol), a non-specific serine protease inhibitor, is successfully used to reduce excessive postoperative bleeding in such patients. The aim of our study was to verify the hypothesis whether aprotinin used during cardiopulmonary bypass procedure affects hemostatic parameters, which might be crucial for the elevated risk of thromboembolic complications.


METHODS
The group of 54 patients subjected to coronary artery surgical treatment included 30 patients, who were given intraoperatively 3 million KIU aprotinin each, and 24 subjects non-treated with aprotinin. Aliquots of blood were withdrawn at several time intervals, until the 5th day after the operation. Whole blood platelet activation and reactivity (the expressions of P-selectin and glycoprotein Ib) were monitored by means of flow cytometry. In addition, several plasma parameters, like PAI-1, t-PA, D-dimers, prothrombin fragment F1 + 2, fibrinogen, ATIII activity, troponin I and CK-MB, as well as platelet count were determined at each time point.


RESULTS
In this study we confirmed the essential advantage of the use of aprotinin: both the postoperative blood drainage and the blood units to be transfused postoperatively to cardiosurgical patients were vastly reduced in the aprotinin-treated subjects. The enhanced overall frequency of perioperative myocardial infarction events was not attributed to this group of patients, nor the non Q-wave infarctions were observed more often in patients treated with aprotinin. In these patients, fibrinolysis parameters tended to be depressed (with increased PAI-1 dominating over elevated t-PA) on the first day after the operation, and no significant differences with regard to fibrinogen, prothrombin fragment F1 + 2, troponin I and platelet count. There was a continuous rise in D-dimers in all the postoperative patients, which lasted until the third day and tended to reach plateau at the 5th day after the operation. We failed to reveal the preventive effects of aprotinin on platelet function: both platelet activation and reactivity remained apparently unchanged. Overall, our results rather support the reasoning on the advantageous effects of low doses of aprotinin. The use of this inhibitor reduces the risk of postoperative undesirable bleeding and results in a decreased postoperative drainage and reduced transfused blood units. On the other hand, however, a higher incidence of perioperative Q-wave infarction in the aprotinin-treated patients, although purely apparent and not statistically significant, might question the unlimited safety of the use of aprotinin in cardiovascular operations.
Golański
R
R
Anesthesiology and Intensive Care Unit, Medical University of Łódź, Poland.
Golański
J
J
Chizyński
K
K
Iwaszkiewicz
A
A
Zasłonka
J
J
Pietrucha
T
T
Chrul
S
S
Watała
C
C
D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage* / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013923:Thromboembolism / Q000209:etiology
D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin