Platelets and Complement Activation in Coronary Artery Bypass Graft Surgery (CABG)

Platelets and Complement Activation in Coronary Artery Bypass Graft Surgery (CABG)

Patients undergoing coronary artery bypass graft surgery (CABG) frequently exhibit postoperative bleeding complications which are still a major cause for morbidity and mortality. One major contributing factor is the loss of platelets and impaired platelet function. During cardiopulmonary bypass (CPB) blood comes in close contact with foreign surfaces which induces a series of reactions; especially the complement system as part of the innate immunity is highly activated. Due to the strong crosslink between complement system, platelet function and the plasmatic coagulation it is likely that complement activation during CPB has an impact on the overall process of clot formation. Besides the activation of the complement system there is growing evidence that the occurrence of mitochondrial DNA (mtDNA) during CPB might be related to further platelet activation . Activated platelets may enhance micro-thrombosis leading to organ failure and thereby contributing to postoperative morbidity.

One major complication during and after CABG surgery is bleeding requiring transfusion and even reoperation in about 2%- 8% of patients.

As bleeding complications increase patient morbidity and mortality, this study is designed to investigate the possible mechanisms of platelet loss during CABG.

The hypothesis is that increased complement activation during CPB leads to platelet activation and loss of platelets. Further the degree of complement activation and levels of mtDNA might correlate with postoperative bleeding, transfusion requirements and clinical outcome.

2.1. Primary Study Objective The aim of the study is to examine the correlation between complement activation (c5b-9) and platelet decline during elective coronary artery bypass graft (CABG) on cardiopulmonary bypass (CPB).

2.2. Further Study Objectives A secondary aim of the study is to investigate the specific pathway of complement activation, the mtDNA levels and the interaction with platelet function.

Therefore correlations between levels of complement factors [c5b-9, C1q (C1r/C1s), C3a, C5a, MBL, Factor B, Factor D], mtDNA level [human NADH dehydrogenase 1 gene] and platelet function [MPV/PTC ratio and FACS for platelet activation factor 4 (PFA)] will be examined.

Further it will be explored whether the level of complement activation and levels of mtDNA and the plasmatic coagulation system correlate with transfusion requirements, postoperative morbidity (need for revision surgery, cardiovascular events including thromboembolic events, sepsis, single or multiple organ failure according to SOFA Score), and in hospital mortality.

There will be also a correlation conducted between levels of complement [see above] and concentration of coagulation factors [F I - F XIII, FXa, FXIIa, Kallikrein, Bradykinin, endogenous thrombin potential (ETP)], transfusion requirements, mtDNA and platelet function to postoperative morbidity (need for revision surgery, cardiovascular events including thromboembolic events, sepsis, single or multiple organ failure according to SOFA Score) and in hospital mortality.

Inclusion Criteria:

I.1. Male and female subjects > 18 years and < 86 years I.2. elective coronary artery bypass graft surgery with or without valve surgery (max. 2 valves) and elective valve surgery (max. 2 valves) on cardiopulmonary bypass (CPB) I.3. ASA I - IV I.4. written informed consent

Exclusion Criteria:

E.1. emergency CABG with or without cardiac valve surgery and emergency valve surgery and emergency aortic dissection E.2. preexisting complement deficiency syndromes E.3. preexisting thrombocytopathy or thrombocytopenia (platelet count below 100 G/L) E.4. Known history of congenital coagulopathy E.5. Patients that are known to be pregnant E.6 Known participation in another interventional clinical trial