Antiplatelet agents and bleeding after cardiac surgery.

Abstract

To the Editor: Pothula et al. (1) suggest that combined antiplatelet and anticoagulant therapy administered prior to coronary artery bypass surgery minimizes microvascular coagulation to a greater degree than either therapy alone. This hypothesis is neither supported by their observational data, nor by the referenced PRISM-PLUS trial, in which improved ischemic, not hemostatic outcomes, were demonstrated (2). The medical treatment of ischemia is not arbitrary, and thus one cannot ignore that the three groups in this study are not comparable, as evidenced by statistical differences in cardiopulmonary bypass (CPB) times, aortic cross-clamp times, temperature, and pre-operative fibrinogen levels. Fibrinogen is an acute phase reactant and could be elevated as a nonspecific marker of a proinflammatory process (3). Higher fibrinogen levels alone, in the clopidogrel + heparin group could account for the lower chest tube drainage (CTD) in this group by improving platelet aggregation. Fibrinogen is the ligand that binds to the GPIIb/IIIA receptor (rendered partially inactive during clopidogrel therapy). Higher fibrinogen levels after CPB have been suggested to protect against excessive bleeding after cardiac surgery (4). The positive correlations that Pothula et al. demonstrated between pre-operative and postoperative fibrinogen levels merely reflect the dilutional effect of CPB. The implication of these results and their validity need to be questioned, since the Pearson’s correlation coefficient is used for independent parameters, not related ones. To suggest that “addition of a preoperative heparin infusion . . .appeared to prevent the excess blood loss,” or that “the combination of a platelet ADP inhibitor and heparin infusion avoided the excess blood loss . . .and resulted in higher plasma fibrinogen levels” is presumptuous for an observational study. It is more likely that the higher preoperative fibrinogen levels were responsible for the higher postoperative fibrinogen levels, rather than any causative effect of heparin. Without quantification of antiplatelet or anticoagulant effects, and a 15% incidence of resistance to thienopyridine agents (5), the authors cannot postulate any mechanistic effects (6,7). Furthermore, IV heparin is not a complete anticoagulant and does not eliminate intravascular coagulation as suggested (8). Platelet activation and heparin resistance (9) may actually increase micro-vascular coagulation. Finally, the elimination of five patients who were transfused excessively during surgery is troubling. The authors state “. . . blood products would confound the relationship between the preoperative prophylactic regimen and postoperative blood loss.” In which direction would it confound? Would transfused patients have lower CTD because they had hemostatic factors replaced, or would they have higher CTD because they are “bleeders”? One wonders what drug regimen these five patients received and how the analysis would have differed if their results were included in the analysis. Linda Shore-Lesserson, MD Department of Anesthesiology, Mt. Sinai Medical Center, New York, NY Kenichi A. Tanaka, MD Jerrold H. Levy, MD Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA