Antiplatelet Drugs: Mechanisms and Risks of Bleeding Following Cardiac Operations

Abstract

Preoperative antiplatelet drug use is common in patients undergoing coronary artery bypass grafting (CABG). The impact of these drugs on bleeding and blood transfusion varies. We hypothesize that review of available evidence regarding drugrelated bleeding risk, underlying mechanisms of platelet dysfunction, and variations in patient response to antiplatelet drugs will aid surgeons as they assess preoperative risk and attempt to limit perioperative bleeding. The purpose of this review is to (1) examine the role that antiplatelet drugs play in excessive postoperative blood transfusion, (2) identify possible mechanisms to explain patient response to antiplatelet drugs, and (3) formulate a strategy to limit excessive blood product usage in these patients. We reviewed available published evidence regarding bleeding risk in patients taking preoperative antiplatelet drugs. In addition, we summarized our previous research into mechanisms of antiplatelet drug-related platelet dysfunction. Aspirin users have a slight but significant increase in blood product usage after CABG (0.5 U of nonautologous blood per treated patient). Platelet adenosine diphosphate (ADP) receptor inhibitors are more potent antiplatelet drugs than aspirin but have a halflife similar to aspirin, around 5 to 10 days. The American Heart Association/American College of Cardiology and the Society of Thoracic Surgeons guidelines recommend discontinuation, if possible, of ADP inhibitors 5 to 7 days before operation because of excessive bleeding risk, whereas aspirin should be continued during the entire perioperative period in most patients. Individual variability in response to aspirin and other antiplatelet drugs is common with both hyper-and hyporesponsiveness seen in 5 to 25% of patients. Use of preoperative antiplatelet drugs is a risk factor for increased perioperative bleeding and blood transfusion. Point-of-care tests can identify patients at high risk for perioperative bleeding and blood transfusion, although these tests have limitations. Available evidence suggests that multiple blood conservation techniques benefit high-risk patients taking antiplatelet drugs before operation. Guidelines for patients who take aspirin and/or thienopyridines before cardiac procedures include some or all of the following: (1) preoperative identification of high-risk patients using point-of-care testing; (2) withdrawal of aspirin or other antiplatelet drugs for a few days and delay of operation in patients at high risk for bleeding if clinical circumstances permit; (3) selective perioperative use of evidence-based blood conservation interventions (e.g., short-course erythropoietin, off-pump procedures, and use of intraoperative

Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor

“…Clinically, perioperative treatment with glycoprotein IIb/IIIa antagonists is known to potentially cause significant bleeding complications and the use and time of drug administration has to be chosen carefully. In contrast, the 6B4 Fab antibody fragment inhibits shunt‐associated platelet aggregation in vivo in baboons without causing thrombocytopenia (10% decrease of platelet counts) or prolongation of bleeding time , features suggesting that GPIb blockade will prove safe to use during surgery.…”

Society of Interventional Radiology Consensus Guidelines for the Periprocedural Management of Thrombotic and Bleeding Risk in Patients Undergoing Percutaneous Image-Guided Interventions—Part II: Recommendations

“…Patient comorbidities (eg, renal function) should be taken into account, and, for patients who present with complex medical comorbidities, multidisciplinary shared decision-making with the patient's cardiovascular specialist or hematologist is recommended for the management of antithrombotic agents, including bridging options, in the periprocedural period. Table 6 (32)(33)(34)36,(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128) summarizes agent-specific recommendations for periprocedural medication interruption and reinitiation, including recommendations for patients with renal impairment (39,43,(129)(130)(131)(132)(133)(134)(135)(136)(137). The recommendations are extrapolated from a compilation of expert consensus recommendations from the cardiology, anesthesia, interventional, and surgical literature (3,6,36,50,138).…”

Antithrombotic Drugs: Pharmacology and Implications for Dental Practice

“…Although complete reversal of antiplatelet influence requires~10 days, bleeding times return to normal after interrupting aspirin therapy for only 4-5 days. 11,12 Preoperative assessment of platelet function, eg, PFA-100, cannot be recommended routinely but could prove useful in exceptional cases, such as urgent management of oral-maxillofacial trauma in a patient taking dual antiplatelet regimens. Low platelet activity does not promise excessive bleeding, but moderate to normal activity will assure it unlikely for any bleeding to result from inadequate platelet function.…”