Acetaminophen, which is a weak inhibitor of platelet cyclooxygenase 1, has a dose-dependent antiaggregatory effect. This property may become clinically significant in patients with intrinsic or drug-induced impairment of hemostasis.

N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but in experimental studies it has been shown to impair coagulation. Since very little is known about the effects of NAC on blood coagulation in surgical patients, we studied its effects during abdominal aortic reconstruction. NAC (a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the same volume of placebo was given intravenously, in a randomized double-blinded fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet aggregation were studied during and after surgery. Total blood loss was also measured. The median (25th-75th percentiles) decrease of the prothrombin time value was 33.0% (30-37%) after NAC treatment and 6.5% (4-8%) after placebo (P<0.001). Postoperative prothrombin time values remained lower in the patients receiving NAC. In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC (P=0.02). Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin time values before and after bolus infusions were associated with increased blood loss (P=0.008 and P=0.015, respectively). NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.

The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.