The purpose of this study was to evaluate the influence of APT on postoperative bleeding and transfusion rates in patients undergoing CABG on CPB. Furthermore, it was determined if different application regimens (single or combined) or different lengths of APT free intervals, prior to surgery (<3, 3-5 and 6-7 days), affect the parameters mentioned above. We observed more chest tube drainage, and higher amounts of blood products transfused (particularly platelets) in all patients who received APT than in CON patients (without APT for at least 8 preoperative days). Differences to CON patients were significantly more pronounced for APT patients with only short APT free intervals (<3 days). The intake of an ADP antagonist, in addition to aspirin, had no further influence on bleeding and transfusion rates.
Though our results are in accordance with recent reports on the perioperative influence of APT [1,6,26] including a meta-analysis on 49 590 patients , some investigations denied any relation between preoperative APT and transfusion requirements. Provided that the preoperative bleeding time was normal, Rawitscher and colleagues  reported no association between preoperative aspirin ingestion and blood loss, which agreed with Vuylsteke and colleagues  also reporting no increased blood loss or transfusion requirements after recent APT with aspirin. However, only a few patients of the cohorts, examined in these studies, had received aspirin within 2 days of surgery, making a comparison to our data problematic.
When analysing blood loss and transfusion demands in CABG, the intraoperative antifibrinolytic regimen should also be taken into account. In our study, significantly more CON patients than APT patients received aprotinin, reported to be superior over tranexamic acid in decreasing intraoperative blood loss . However, as shown recently in a prospective randomized trial performed in our centre , higher transfusion demands due to elevated blood loss were not prevented by the use of aprotinin instead of tranexamic acid. Moreover, a recent investigation of Mangano and colleagues , involving 4374 patients undergoing operative revascularization reported similar efficacies of aprotinin vs. tranexamic acid and aminocaproic acid in reducing blood loss. Therefore, we do not believe that the significant differences in bleeding rates and transfusion requirements observed in our study could have resulted from differences in the intraoperative antifibrinolytic regimen.
Regarding potential study limitations, one should note the inhomogeneity of our study groups with respect to the antifibrinolytic regimen used. More by chance (due to the preference of the respective surgeon) than by any kind of selection, aprotinin was administered more often to CON than to APT patients (36 vs. 27, P = 0.027, Table 2). This could probably have biased blood loss, but also has accounted for the higher frequency of cardiovascular events observed with CON patients. A recent investigation, involving 3013 patients undergoing primary cardiac surgery, gave evidence that aprotinin, and not tranexamic acid, was associated with a dose-dependent multiorgan damage affecting the kidneys (doubling to tripling in the risk of renal failure), the heart (55% increase in the risk of AMI and heart failure) and the brain (181% increase in the risk of stroke or encephalopathy) . Unlike tranexamic acid, aprotinin shows high affinity for the kidneys and impairs the endothelium-derived relaxation by inhibition of nitric oxide synthesis and release. Together with the inhibition of plasmin and activated protein C, this may promote formation of disseminated platelet-fibrin thrombin as shown recently upon the examination of patients who had received aprotinin .
In conclusion, this study has demonstrated higher bleeding and transfusion demands in APT compared to CON patients. In turn, the beneficial effect of APT on perioperative CK-MB values and infarction rates was underlined, particularly in patients with continuous treatment or only short APT free intervals (<3 days).
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