Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) nonspecifically inhibit cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and COX-2, which mediates inflammatory response mechanisms. Celecoxib, an antiarthritic agent that inhibits COX-2 but spares COX-1 at therapeutic doses, is expected to have minimal effects on platelet function. A double-blind, randomized, placebo-controlled study of 10 days' duration was conducted in 24 healthy adults to compare the effects on platelet function of a supratherapeutic dose of celecoxib (600 mg bid) with a standard dose of naproxen (500 mg bid), a conventional NSAID. Ex vivo platelet aggregation in response to standard agonists (collagen, arachidonate, or U46619 [a thromboxane A2 receptor agonist]), bleeding time, and serum thromboxane B2 (TxB2) level were measured. Unlike celecoxib or placebo, naproxen produced statistically significant reductions in platelet aggregation and serum TxB2 levels and increased bleeding time. The results indicate that even at supratherapeutic doses, celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX-1 sparing relative to conventional NSAIDs.

Effects of Celecoxib, a Novel Cyclooxygenase-2 Inhibitor, on Platelet Function in Healthy Adults: A Randomized, Controlled Trial

The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting.

Aspirin and nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs) inhibit platelet cyclooxygenase, thereby blocking the formation of thromboxane A2. These drugs produce a systemic bleeding tendency by impairing thromboxane-dependent platelet aggregation and consequently prolonging the bleeding time. Aspirin exerts these effects by irreversibly blocking cyclooxygenase and, therefore, its actions persist for the circulating lifetime of the platelet. Nonaspirin NSAIDs inhibit cyclooxygenase reversibly and, therefore, the duration of their action depends on specific drug dose, serum level, and half-life. The clinical risks of bleeding with aspirin or nonaspirin NSAIDs are enhanced by the concomitant use of alcohol or anticoagulants and by associated conditions, including advanced age, liver disease, and other coexisting coagulopathies.

/pdf/effects-of-nonsteroidal-antiinflammatory-drugs-on-platelet-42bx9web0d.pdf

Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis.

This study examines the surgical practice at the Wessex Neurological Centre over the 5-year period from 1989 to 1993 to determine the incidence of postoperative hematoma and to identify risk factors for a perioperative bleeding disorder. The study includes only those postoperative hematomas (at any site) that followed and were related to a neurosurgical operation and were surgically evacuated. The study is prospective for the year 1993 and retrospective for the preceding years. Over the 5 years, 6668 operations were performed and 71 postoperative hematomas were surgically evacuated, accounting for an overall rate of 1.1% of operations. The records were available for 69 cases. The most frequent diagnosis leading to postoperative hematoma was meningioma surgery with a rate of 6.2% of cases (13 of 211); followed by craniotomy for trauma, 3.7% (7 of 192); aneurysm surgery, 2.6% (11 of 428); and intrinsic supratentorial tumors, 2.2% (10 of 451). Postoperative hematomas were intraparenchymal in 43% of cases, subdural in 5%, extradural in 33%, mixed in 8%, and confined to the superficial wound in 11%. The overall mortality was 32% (37% for intraparenchymal and 12% for extradural). Risk factors for a perioperative bleeding disorder were present in two-thirds of the patients. Administration of antiplatelet agents (aspirin and nonsteroidal anti-inflammatory drugs) was the most commonly associated risk factor. At least 75% of these identified risk factors could potentially have been avoided or corrected.

Postoperative hematoma: a 5-year survey and identification of avoidable risk factors.

The purpose of this study was to prospectively evaluate whether heparin and protamine doses administered using a standardized protocol based on body weight and activated clotting time values are associated with either transfusion of hemostatic blood products (HBPs) or excessive postoperative bleeding. Analysis using 10 multiple logistic or linear regression models in 487 cardiac surgical patients included perioperative variables that may have an association with either transfusion of HBP and/or excessive postoperative chest tube drainage (CTD). Prolonged duration of cardiopulmonary bypass (CPB), lower pre-CPB heparin dose, lower core body temperature in the intensive care unit, combined procedures, older age, repeat procedures, a larger volume of salvaged red cells reinfused intraoperatively and abnormal laboratory coagulation results (prothrombin time, activated partial thromboplastin time, and platelet count) after CPB were associated with both transfusion of HBP and increased CTD. Female gender, lower total heparin dose, preoperative aspirin use and the number of HBPs administered intraoperatively were associated only with increased CTD, whereas a larger total protamine dose was associated only with perioperative transfusion of HBPs. Preoperative use of warfarin or heparin was not associated with excessive blood loss of perioperative transfusion of HBPs. In contrast to previous studies using bovine heparin, data from the present study do not support the use of reduced doses of porcine heparin during CPB.

Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients.

We performed a case-control study to estimate the relative risk of reoperation for bleeding in coronary artery bypass graft patients who had taken aspirin within the 7 days preceding sur gery. Comparison of 90 cases of reoperation with 180 matched control subjects gave an estimated odds ratio for reoperation of 1082 (95% confidence interval, 1.23 to 3.32). Although their preop erative coagulation values were similar, cases used significantly more whole blood (cases, 9.5 + 5.2 units; control subjects, 3.0 + 2.0 units; median + interquartile range), packed red blood cells (cases, 2.1 + 4.0 units; control subjects, 0.9 +- 2.0 units), and platelets (cases, 12.2 +- 12.0 units; control subjects, 2.9 +- 4.0 units) than control subjects. Cases had intensive care unit stays of 4.7 +- 5.7 days (mean SD) vs 2.1 1.9 days for control subjects and postoperative hospitalizations of 10.9 +- 8.2 days vs 7.0 +- 3.2 days for control subjects. We conclude that aspirin exposure within 7 days before coronary bypass surgery is asso ciated with an increased rate of reoperation for bleeding and that reoperation is associated with large increases in transfusion requirements and intensive care unit and hospital stays. (Arch Intern Med.1991;151:89-93)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=intemed&articleId=614444&pdfFileName=archinte_151_1_014.pdf

Preoperative Aspirin Therapy and Reoperation for Bleeding After Coronary Artery Bypass Surgery

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Preoperative Aspirin Therapy and Reoperation for Bleeding After Coronary Artery Bypass Surgery

Preoperative Aspirin Therapy and Reoperation for Bleeding After Coronary Artery Bypass Surgery