The present data suggest that the CAT variables ETP and peak thrombin correlate well with the clinically observed bleeding tendency postoperatively in cardiac surgical patients. Patients of group 2 had a significantly lower ETP and peak thrombin, both pre (PRP and PPP) and post CPB (only PRP), than patients in group 1. Concerning the other laboratory parameters, platelet number was the only individual variable measured pre-CPB predicting blood loss postoperatively. Post CPB, besides low fibrinogen a low platelet number was also predictive for blood loss.
Recently Coakley and co-workers demonstrated that TG both pre- and postoperatively could potentially be used to identify patients at an increased risk of bleeding post-CPB . However, they only measured TG in PPP, excluding the influence of platelets, which play a very important role in maintaining normal haemostatic function. It is more representative of the in vivo situation to include the procoagulant functions of platelets .
Conventional clot-based methods, have the disadvantage of measuring only the moment of clot formation and ensuing changes in the properties of the clot. Clot formation is only one of the many functions of thrombin and not necessarily the most important one. Thrombin also activates platelets, and furthermore, besides procoagulant effects it has also anticoagulant effects following its binding to thrombomodulin. Ex vivo TG tests, like CAT, measure the haemostatic function of the blood, determined by simultaneous prothrombin activation and thrombin inactivation : it measures the remaining capacity of blood to generate a thrombin burst indicating an increased risk of thrombosis or bleeding . In contrast, in vivo TG, revealed by products like prothrombin fragment F1+2, thrombin antithrombin complex, and d-dimers, provides indications of TG that has already occurred  at the moment of blood collection.
Since the lag time represents the same aspect as in standard coagulation assays, this is comparable with aPTT and PT. Our results showed that both aPTT and PT as well as lag time were not different between the groups. These tests terminate with endpoints that occur with less than 5% of the reaction complete . Apparently, the present data strengthen the notion that it is not the initiation phase of clotting but the propagation phase that determines haemostasis and blood loss after cardiac surgery.
Time to peak, also a time dependent variable, also did not show any significance in predicting blood loss. Peak thrombin and ETP, reflecting the amount of thrombin generated, give a more accurate evaluation of coagulability.
In group 2, patients had a lower mean platelet number both before heparinisation and after protamine administration. Platelets are important in the blood coagulation process and play an important role in TG by providing a procoagulant membrane surface, and hence supporting the formation of more thrombin . We observed in this study that reduced platelet count was also predictive of blood loss although the latter outcome occurs within the normal ranges of platelet count. It is worth noting however that platelet count cannot detect abnormality in the coagulation system. CAT, in contrast, is a global functional test that reflects the coagulation profile of the patient in the absence and presence of platelets. Bleeding tendency is related to the hemostatic conditions in pro- and anticoagulant factors, platelets, vessel wall and the fibrinolytic system. TG in PRP reflects the major part of this physiological clotting system, including the interaction between platelets and the clotting system.
Concerning coagulation factors we only measured fibrinogen. This factor demonstrated to be higher both pre- and postoperatively in group 1, but the difference was only statistically significant postoperatively. In the study of Coakley  coagulation factor levels were determined postoperatively in groups that either bled more than 1L or less than 1L. Fibrinogen level was the same in both groups, in contrast with our results. Karlsson et al.  investigated the relationship between preoperative fibrinogen plasma concentration and postoperative bleeding after CABG surgery. Their main finding was that higher preoperative fibrinogen was correlated with less blood loss postoperatively. Despite of the important contribution of fibrinogen in the coagulation process, our study results indicate that fibrinogen level is less strongly associated with blood loss than TG parameters. This is remarkable because, although fibrinogen is depleted before 5% of all thrombin is formed , thrombin bound to fibrin has a positive feedback activation on the coagulation system and is protected from inactivation to the action of antithrombin and heparin .
Remarkable is the significantly higher dose of intraoperative heparin in group 1. Most probably a higher dose of heparin is administered in this group as a result of a relatively high platelet count in this group : the concentration of heparin required to inhibit or delay coagulation is directly related to the number of platelets , probably due to the capacity of platelet released platelet factor 4 neutralizing heparin [19, 20].
Patients who bled more, were administered proportionally less crystalloids and more colloids. Colloids are known to affect clot formation by reducing fibrinogen concentration and disturbing fibrin polymerization  demonstrated by thromboelastography assay. Schols et al. found that colloids reduce the formation of fibrin clots but affect TG only at clinically irrelevant high concentrations . The volume of colloids administered was not significantly different between the groups.
Group 2 is characterized by a higher supplementation of transfusion products. In addition, these patients had a higher intraoperative blood loss, as shown by a higher amount of PRC volume processed by cell salvage. Despotis et al. also demonstrated that greater volumes of intraoperative salvaged red cells were associated with excessive blood loss and use of blood products , explained by the fact that greater volumes of salvaged red cells primarily reflects excessive blood loss intraoperatively but proceeding postoperatively. Another explanation may be that extensive intraoperative cell salvage caused a significant loss of platelets and plasma resulting in postoperative bleeding.
The strength of this study is that CAT, performed preoperatively, is able to predict blood loss after cardiac surgery. Preoperative measurements (T1) exclude the haemostatic effects caused by exposure of the blood to different non-physiological conditions. The predictive value of CAT performed postoperatively (T2) for blood loss will be influenced by a lot of interventions like heparinisation, fluid administration (crystalloid and/or colloid), administration of tranexamic acid and protamine, time on bypass, and transfusion product requirements intraoperatively. All these factors interfere at different levels in the haemostatic balance of the patients what makes the prediction of blood loss by CAT parameters weaker at T2 (AUCs are lower at T2).
The main limitation of the study is the low number of participants (n=30). P-values in the multivariate linear regression models were higher or even no longer statistically significant, possibly due to small sample size. The results should be considered as preliminary. Changes in haemostatic factors would have been more reliable in a larger number of patients. Another limitation of the study is that it could not account for variations in routine practice in the ICU that may have influenced blood loss, such as amount and timing of platelet and plasma transfusions. Especially in the bleeding group the amount of blood loss should be influenced by platelet and plasma transfusion. Therefore, additional larger clinical, and preferable intervention, studies are required to establish profound clinical relevance.