Activation of hemostasis after off-pump coronary artery bypass graft surgery

The aim of this thesis was to study the activation of hemostasis and inflammation, in patients undergoing off-pump (OPCAB) and on-pump coronary artery bypass graft (CABG) surgery and the relationship of coagulation and inflammation to clinical outcome. We hypothesized that activation of hemostasis and C-reactive protein (CRP) would be more pronounced in patients undergoing CABG using cardiopulmonary bypass (CPB) and that this would be associated with increased morbidity. In particular, neurocognitive dysfunction may be less pronounced in patients undergoing OPCAB procedures. Therefore, we did a number of studies in which we investigated several aspects of hemostasis in patients undergoing on- and off-pump CABG. Moreover, the influence of CRP as a marker of inflammation was studied as others have already demonstrated that CRP levels may be associated with increased morbidity after cardiac surgery. In 40 patients, randomly assigned to off-pump and on-pump CABG, we observed that CABG surgery with CPB was associated with increased thrombin generation and fibrinolytic activity in the immediate postoperative period. However, patients in the OPCAB-group demonstrated a delayed postoperative response that became equal in magnitude to the CPB group in the later (20-96 hours) postoperative period. Although early postoperative activation of hemostasis was more pronounced after on-pump CABG, we did not find any association with clinical outcome in the initial group and in a larger group of 73 CABG patients. Therefore, the clinical impact of CPB-related activation of coagulation remains to be determined. In contrast to our hypothesis, a significant association between early postoperative activation of hemostasis and the incidence of early postoperative cognitive decline was observed in 60 OPCAB patients. D-dimer levels and prothrombin fragments 1.2 at two hours after the off-pump procedure were strongly associated with early cognitive decline on postoperative day 4. Several mechanisms may be responsible for this apparent paradox. One contributing factor may be the fact that institution of CPB can obviously reduce the hypercoagulable state resulting from surgical trauma. In 60 on- and off-pump patients, we could demonstrate that von Willebrand Factor (VWF) release is increased after both procedures. However, VWF activity is significantly lower in the on-pump group. Shear stress-induced proteolysis due to the use of CPB may be one important factor responsible for this phenomenon. In the Octopus Study, the majority of the OPCAB patients received thoracic epidural analgesia (TEA) in combination with general anesthesia. Postoperative activation of hemostasis may be affected by the use of TEA. We conducted a trial where we studied the effects of several LA on Tromboxane A2-induced platelet aggregation in an in vitro model. However, the LA tested had only limited ability to inhibit that Tromboxane A2-induced platelet aggregation. We were unable to demonstrate a significant interaction between CPB-induced activation of hemostasis, the inflammatory response to surgery and CPB and parameters of clinical outcome. We indeed observed an association between baseline CRP levels, a marker for chronic inflammation, and postoperative atrial fibrillation after both on-pump and off-pump CABG. Apparently, the relationship between postoperative CRP activation and the incidence of atrial fibrillation is not CPB-dependent.