Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting

Abstract

In a previous study, preoperative levels of activated protein C (APC) were associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the cofactor of activated protein C, has activated protein C-independent anticoagulant activity and cytoprotective effects. Therefore, the objective of this study was to test whether preoperative, baseline levels of either thrombin or protein S were associated with hemodynamic performance or markers of myocardial damage after CABG. One hundred patients undergoing elective on-pump CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin generation) and free protein S were measured preoperatively and cardiac index, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were measured serially thereafter at fixed time points. Cardiac biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse correlation between preoperative F1+2 and free protein S levels (r= -0.30, p=0.003). High preoperative F1+2 and low preoperative protein S levels were associated with a less favorable hemodynamic profile postoperatively. Patients with F1+2 in the highest decile (≥0.85 nmol/l) and patients with preoperative protein S in the lowest decile (≤63%) had lower CI values, and higher pulmonary and systemic vascular resistance index values postoperatively than comparison patients. Preoperative F1+2 or protein S did not correlate with postoperative cardiac biomarker levels. Baseline activation of coagulation and the balance between pro-coagulant and anti-coagulant factors preoperatively might have implications for postoperative hemodynamic recovery after CABG.

Towards standardization of thrombin generation assays: Inventory of thrombin generation methods based on results of an International Society of Thrombosis and Haemostasis Scientific Standardization Committee survey

“…1 Nowadays, many semi-and fully automated assays are on the market to measure TG in platelet poor (PPP) and platelet rich plasma (PRP), as well as in whole blood. [5][6][7] TG can be used to monitor the hemostatic system, 5,[8][9][10][11][12][13][14] to investigate the contribution of natural pro-and anticoagulants to hemostasis, and to study the effect of drugs interfering with coagulation. 5,15,16 Depending on the research question, TG should be performed in either PPP or PRP.…”

“…TG can be used to monitor the hemostatic system, 5,8‐14 to investigate the contribution of natural pro‐ and anticoagulants to hemostasis, and to study the effect of drugs interfering with coagulation 5,15,16 . Depending on the research question, TG should be performed in either PPP or PRP 1,17 .…”

Safety outcomes of anti-platelet therapy post coronary artery bypass graft surgery: A systematic review and network meta-analysis of randomized control trials

“…3 Preoperative high prothrombin fragments and low protein S levels are linked with a less satisfactory hemodynamic profile postoperatively. 4 Antiplatelets have been demonstrated to obtain better cardiovascular outcomes, making them a therapeutic mainstay after CABG. 5 Aspirin is the most commonly prescribed antiplatelet following CABG 6 as it considerably reduces the risk of mortality and subsequent incidence of myocardial infarction (MI) and stroke if started 6-48°hours after CABG.…”

“…3 Preoperative high prothrombin fragments and low protein S levels are linked with a less satisfactory hemodynamic profile postoperatively. 4 Antiplatelets have been demonstrated to obtain better cardiovascular outcomes, making them a therapeutic mainstay after CABG. 5…”