The role of the protein C-thrombomodulin system and fibrinolysis during cardiovascular surgery: Influence of acute preoperative plasmapheresis

Abstract

Objectives: To assess the benefits of withdrawn autologous plasma, the objective of this study was to investigate whether withdrawal of acutely performed platelet-rich or platelet-poor plasmapheresis allays changes in the protein C-thrombomodulin and fibrinolytic systems after retransfusion secondary to cardiopulmonary bypass (CPB). In addition, the 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 elective aortocoronary bypass patients. Design: The investigation was scheduled as a prospective, randomized, unblinded study. Setting: This single investigation was conducted in the Department of Anaesthesiology and Intensive Care Medicine at a university in Germany. The study protocol was approved by the Ethics Committee of the hospital, and informed consent was obtained. Participants: Sixty male patients scheduled for elective coronary artery bypass grafting with extracorporeal circulation were included in the study. Interventions: APP was performed between induction of anesthesia and incision, collecting either 10 mL/kg of autologous platelet-poor plasma (PPP patients, group 1; n = 20) 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 on their usual regimen of cardiac drugs until the morning of surgery. To preserve hemodynamic stability and restore the intravascular oncotic pressure, the separated plasma was replaced by infusion of an equal amount of hydroxyethyl starch solution (HES) (6% HES, molecular weight 2 × 10 5, substitution rate 0.5%). In all operations, the same surgical procedure was chosen. For all patients, induction and maintenance of anesthesia were similar, consisting of weight-related doses of fentanyl (35 μg/kg), midazolam (0.65 mg/kg), and pancuronium bromide (0.15 mg/kg). The lungs of all patients were mechanically ventilated during the first 5 hours after the end of the operation. Measurements and Main Results: All patients had serial coagulation studies including antithrombin (AT) III-activity, prekallikrein, factor XII, and immunologic tests such as thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C and S (PC and PS), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide Bβ 15–42 (FPBβ 15–42), D-dimers, and hemoglobin and platelet counts determined intraoperatively and postoperatively. 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 ± 12 × 10 9/L (PPP group) and 245 ± 36 × 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 concentrations of TAT and FPA increased (ranging from +185% to +340% from baseline values) and AT III-activity, PC, PS, and TM antigen decreased (ranging from −8% to −55% from baseline values) to a different extent for all three groups throughout CPB. t-PA-activity increased with a maximum 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 fibrinogen degradation markers such as D-dimers and FPBβ 15 to 42 occurred in peak concentrations after neutralization of heparin by protamine. Only PRP patients showed baseline concentrations of coagulation parameters the next morning ( p < 0.05). Total postoperative blood loss within the first 24 hours reached 482 ± 273 mL (PRP group), 775 ± 256 mL (PPP group), and 948 ± 342 mL in the control group ( p < 0.05). None of the PRP patients received homologous blood, but one PPP patient received two units and five control patients received nine units of packed red cells ( p < 0.05). Conclusions: The results suggest that in cases of elective cardiac surgery, heparin cannot prevent generation of both thrombin and fibrin throughout CPB and postoperatively. The APP procedure had no negative effect on the quality of autologous plasma. APP-withdrawn PRP did not only increase platelet count effectively but also improved an altered hemostatic system after retransfusion. Because of the beneficial effects of APP-withdrawn PRP, it appears to be an attractive technique, especially in patients in whom withdrawal of autologous whole blood cannot be performed, as well as to reduce allogeneic blood usage and perioperative blood loss.