Transfusion and hemostasis in cardiac surgery

Hemostatic abnormalities occur commonly after cardiac surgical interventions. Changes are linked to inflammatory responses by a network of humoral and cellular components including proteases of the clotting and fibrinolytic cascades. Pharmacologic and nonpharmacologic strategies directed at attenuating and treating hemostatic system activation have been reported in experimental and clinical studies. Patients undergoing cardiac surgery with and without cardiopulmonary bypass (CPB) are at risk for excessive bleeding and associated complications. This bleeding often leads to transfusion of allogeneic blood and hemostatic blood components as well as reexploration. Excessive bleeding after cardiac surgery is related to changes in the hemostatic system secondary to both dilutional and activation and/or consumptive effects on both platelets (PLTs) and coagulation factors. Further compounding the issue of hemostatic abnormalities in cardiac surgical patients is the increasing use of long-acting anti-PLT or antithrombotic agents in this population. Anti-PLT therapy is routinely administered for cardiovascular disorders, especially as related to acute coronary syndromes and cardiologic interventions (e.g., percutaneous transluminal coronary angioplasty, stents), and for managing ischemic stroke. PLT inhibitors, especially the thienopyridines, are increasingly being associated with an increased risk of bleeding, especially in patients undergoing coronary artery bypass graft surgery. Although withdrawing these agents in patients with ischemic cardiovascular disease may decrease perioperative bleeding, it may also lead to adverse consequences as related to ischemic effects, particularly in patients having undergone percutaneous interventions, those with coronary artery stents, and those with unstable angina. Managing these complex patients poses a major problem for clinicians. Pharmacologic interventions have been extensively reported as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Prophylactic administration of agents with antifibrinolytic and anti-inflammatory properties can decrease blood loss and transfusion. Antifibrinolytic agents are the most extensively studied blood conservation agent. On November 5, 2007, the US Food and Drug Administration (FDA) noted that Bayer, the manufacturer of aprotinin (Trasylol), will suspend the marketing of this drug until a comprehensive review of a Canadian study showing an increased risk of death can be performed. The FDA issued a communication in October 2007, describing recommendation to stop patient enrollment in the aprotinin treatment group arm of the: Blood conservation using antifibrinolytics: A randomized trial in a cardiac surgery population (BART) study. This information can be followed at the FDA Web site (http://www.fda.gov/cder/drug/infopage/aprotinin/default.htm). Studies leading up to the randomized Canadian study will be discussed in these series and can be followed on the FDA Web site at http://www.FDA.gov, and are noted currently at (http://www.fda.gov/bbs/topics/NEWS/2007/NEW01738.html). The impact this will have on bleeding, transfusion requirements, and need for blood resources in cardiac surgical patients will be noteworthy to follow. The ability to reduce blood product transfusions and to decrease operative times and reexploration has important implications for patient outcomes, availability of blood products, and overall health care costs. Novel therapies are also under investigation that involve recombinant techniques and may improve our ability to attenuate hemostatic system activation or optimally manage excessive bleeding. At present, the main therapy for cardiac surgical patients who are bleeding involves maintenance of oxygen-carrying capacity with transfusion of allogeneic RBC units and hemostatic blood components to restore hemostasis. Transfusions also pose potential risks and may not always be effective with respect to the management of bleeding. Blood resources are increasingly scarce, and thus blood availability as well as the risk-benefit of blood product administration need to be weighed when considering therapeutic approaches to bleeding in cardiac surgical patients. In September 2005, a CME symposium jointly sponsored by the Dannemiller Memorial Educational Foundation and LMS Group and supported by an educational grant from Bayer Pharmaceuticals Corporation addressed hemostasis and blood management in cardiac surgical patients. That discussion of therapeutic and preventative approaches to these current issues is detailed in this volume, and has been updated to include current perspectives.