Platelets and Complement Activation in Coronary Artery Bypass Graft Surgery (CABG)
Condition: Cardiopulmonary Bypass; Inflammatory Response; Platelet Dysfunction
Study type: Observational [Patient Registry]

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        elective cardiac surgery patients scheduled for CPB procedure meeting the inclusion
        criteria at the University Hospital Innsbruck
      
Keywords: bleeding; transfusion; cardiopulmonary bypass; cardiac surgery; complement system