THE ROLE THE PROTEIN C-THROMBOMODULIN SYSTEM AND FIBRINOLYSIS DURING CARDIOVASCULAR-SURGERY - INFLUENCE OF ACUTE PREOPERATIVE PLASMAPHERESIS

Objectives: To assess the benefits of withdrawn autologous plasma, the objective of this study was to investigate whether withdrawal of acut ely performed platelet-rich or platelet-poor plasmapheresis allays cha nges in the protein C-thrombomodulin and fibrinolytic systems after re transfusion secondary to cardiopulmonary bypass (CPB). In addition, th e study attempted to determine the influence of acute plasmapheresis ( APP) on the protein C-thrombomodulin and fibrinolytic systems as well as on homologous blood consumption and perioperative blood loss in ele ctive aortocoronary bypass patients. Design: The investigation was sch eduled as a prospective, randomized, unblinded study. Setting: This si ngle investigation was conducted in the Department of Anaesthesiology and Intensive Care Medicine at a university in Germany. The study prot ocol was approved by the Ethics Committee of the hospital, and informe d consent was obtained. Participants: Sixty male patients scheduled fo r elective coronary artery bypass grafting with extracorporeal circula tion were included in the study. Interventions: APP was performed betw een induction of anesthesia and incision, collecting either 10mL/kg of autologous platelet-poor plasma (PPP patients, group 1; n = 0) or the same amount of platelet-rich plasma (PRP patients, group 2; n = 20). patients of group 3 (n = 20) had no APP (control group). All patients were maintained an their usual regimen of: cardiac drugs until the mor ning of surgeryl To preserve hemodynamic stability and restore the int ravascular oncotic pressure, the separated. plasma was replaced infusi on of an equal amount of hydroxyethyl starch solution (HES) (6% HES, m olecular weight 2 x 105, substitution rate 0.5%). in all operations, t he same surgical procedure was chosen. For all patients, induction and maintenance of anesthesia were similar, consisting of weight-related doses of fentanyl (35 mu g/kg), anidazolam (0.65 mg/kg), and pancuroni um bromide (0.15 mg/kg). The lungs of all patients were mechanically v entilated during the first 5 hours after the end of the operation. Mea surements and Main Results: All patients had serial coagulation studie s including antithrombin (AT) ill-activity, prekallikrein, factor XII, and immunologic tests such as thrombin-antithrombin III (TAT), fibrin opeptide A (FPA), protein C and S (PC and PS), thrombomodulin (AT), ti ssue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PA I 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimers, and hemo globin and platelet counts determined intraoperatively and postoperati vely. Chest tube drainage and transfusion requirements were recorded; APP had no negative effects on the quality of PPP and PRP plasma. The platelet count of the withdrawn plasma was 28 +/- 28 x 10(9)/L (PPP gr oup) and 245 +/- 36 x 10(9)/L (PRP group). At the end of the operation (after retransfusion of autologous plasma) and on the morning of the first postoperative day, platelet counts were significantly higher (p > 0.05) in the PRP than in the PPP and control groups, Plasma concentr ations of TAT and FPA increased (ranging from + 185% to + 340% from ba seline values) and At ill-activity, PC, PS, and TM antigen decreased ( ranging from -8% to -55% from baseline values) to a different extent f or all three groups throughout CPB. t-PA-activity increased with a max imum:at the end of CPB (PPP group, 6.9 +/- 1.5 IU/mL; PRP group, 3.8 /- 0.8 IU/mL; control group, 10.9 +/- 2.8 IU/mL). Fibrin and fibrinoge n degradation markers such as D-dimers and FPB beta 15 to 42 occurred in peak concentrations after neutralization of heparin by protamine. O nly PRP patients showed baseline concentrations of coagulation paramet ers the next,morning (p < 0.05). Total postoperative blood loss-within the first 24 hours reached 482 +/- 273 mt (PRP group), 775 +/- 256 mL . (PPP group), and 948 +/- 342 mt in the control group (p < 0.05). Non e of the PRP patients received homologous blood, but one PPP patient r eceived two units and five control patients received nine units of pac ked red cells (p < 9.051. Conclusions: The results suggest that in cas es of elective cardiac surgery, heparin cannot prevent generation of b oth thrombin and fibrin throughout CPB and postoperatively. The APP pr ocedure had no negative effect on the quality of autologous plasma. AP P-withdrawn PRP did not only increase platelet count effectively but a lso improved an altered hemostatic system after retransfusion. Because of the beneficial effects of APP-withdrawn PRP, it appears to be an a ttractive technique, especially in patients in whom with drawal of aut ologous whole blood cannot be performed, as well as to reduce allogene ic blood usage and perioperative blood loss. Copyright (C) 1996 by W.B . Saunders Company