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

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.

[1]  R. Lassila,et al.  Thrombin in myocardial ischemia-reperfusion during cardiac surgery. , 2009, The Annals of thoracic surgery.

[2]  J. Griffin,et al.  bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 21, 2013. For personal use only. The cytoprotective protein C pathway , 2006 .

[3]  R. Suojaranta-Ylinen,et al.  Thrombin generation during reperfusion after coronary artery bypass surgery associates with postoperative myocardial damage , 2006, Journal of thrombosis and haemostasis : JTH.

[4]  J. Rosing,et al.  Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Dixon,et al.  Coagulation activation and organ dysfunction following cardiac surgery. , 2005, Chest.

[6]  B. Dahlback.  Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway : novel insights into structure-function relationships and molecular recognition , 2005 .

[7]  S. Kathiresan,et al.  Cardiac troponin T elevation after coronary artery bypass grafting is associated with increased one-year mortality. , 2004, The American journal of cardiology.

[8]  T. van der Poll,et al.  Beyond sepsis: Activated protein C and ischemia–reperfusion injury , 2004, Critical care medicine.

[9]  S. Rezende,et al.  Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex. , 2004, Blood.

[10]  José A Fernández,et al.  Protein S Confers Neuronal Protection During Ischemic/Hypoxic Injury in Mice , 2003, Circulation.

[11]  S. Kathiresan,et al.  A comparison of cardiac troponin T and creatine kinase-MB for patient evaluation after cardiac surgery. , 2002, Journal of the American College of Cardiology.

[12]  J. Meijers,et al.  The Role of Protein S in the Activation of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and Regulation of Fibrinolysis , 2001, Thrombosis and Haemostasis.

[13]  C. Kanthou,et al.  The anticoagulant factor, protein S, is produced by cultured human vascular smooth muscle cells and its expression is up-regulated by thrombin. , 2000, Blood.

[14]  S. Goff,et al.  Signaling through the ARK tyrosine kinase receptor protects from apoptosis in the absence of growth stimulation , 1997, Oncogene.

[15]  K. Kawamoto,et al.  Prevention of growth arrest‐induced cell death of vascular smooth muscle cells by a product of growth arrest‐specific gene, gas6 , 1996, FEBS letters.

[16]  J. Griffin.  The thrombin paradox , 1995, Nature.

[17]  D. Cooper,et al.  Evidence for a protein S receptor(s) on human vascular smooth muscle cells. Analysis of the binding characteristics and mitogenic properties of protein S on human vascular smooth muscle cells. , 1995, The Biochemical journal.

[18]  G. Gasic,et al.  Coagulation factors X, Xa, and protein S as potent mitogens of cultured aortic smooth muscle cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  José A Fernández,et al.  Activation of protein C and hemodynamic recovery after coronary artery bypass surgery. , 2007, The Journal of thoracic and cardiovascular surgery.

[20]  C. Paweletz,et al.  Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells , 2003, Nature Immunology.

[21]  J. Griffin.  Blood coagulation. The thrombin paradox. , 1995, Nature.