DISORDERS OF COAGULATION STATUS AND HAEMOSTASIS AS PROGNOSTIC PARAMETERS OF IMMEDIATE AND EARLY RESULTS AFTER SURGICAL MYOCARDIAL REVASCULARISATION

Surgical myocardial revascularization is one of the most commonly performed surgical procedures in the world. Over time, with the development of technology and modern diagnostic procedures, as well as the advancement of surgical techniques, the mortality rate for elective uncomplicated cases has fallen to below 2%. Nevertheless, despite the exceptional development of the surgical techiniques, the rate of postoperative complications, that can compromise the patients, is over 10%. The aim of this study was to define a group of patients with an increased risk of postoperative complications depending on the disorders of coagulation status and haemostasis. Twenty eight patients who underwent surgical revascularization of the myocardium were included in this prospective, non-randomized study. The study was conducted at the Clinic for Cardiac Surgery, Clinical Center Nis, from January to April 2017. Preoperatively as well as 3 hours, 24 hours, 48 hours, 3 days, and 5 days postoperatively, the following parameters were determined: blood count, inflammation parameters (C reactive protein, presepsin); coagulation status (prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (APTT), fibrinogen, anti-thrombin III, D dimer). The only preoperative independent prognostic parameter for increased postoperative drainage was INR. Activated clothing time (ACT) was an independent postoperative prognostic parameter of increased postoperative drainage, probably due to delayed or prolonged heparin activity. Inflammation parameters showed no association with the onset of postoperative complications. In relation to patients without bleeding, in patients with bleeding, significantly higher values of urea and the difference in APTT values, preoperatively and at the end of the monitoring period, were detected. Multivariate logistic regression analysis, confirmed the difference in APTT values preoperatively and at the end of the monitoring period, as the only factor, significantly associated with the risk of bleeding. Multivariate linear regression analysis, confirmed the value of the urea, as the only factor significantly associated with the change in total allogeneic transfusion value. Increase in urea levels is associated with an increase in the total amount of allogeneic transfusion. Correlation analysis showed that the increased number of days in the intensive care was significantly associated with female gender, number of grafts, prolonged ECC, clamping time, hematocrit (HCT), PT, INR preoperatively and at the end of the follow-up period. Surgical myocardial revascularization is a safe method with a minimal morbidity rate. Using of modern methods for the preoperative monitoring of haemostasis may significantly reduce the risk of postoperative bleeding and the need for transfusion of red blood cells and other blood derivatives. Acta Medica Medianae 2019;58(1):64-81.


Introduction
Cardiovascular (CV) diseases are leading cause of death in most developed countries and in many undeveloped countries.Epidemiological data indicate that CV diseases cause almost half of total mortality, while malignant tumors and lung diseases are represented by 22% and 10%, respectively.Every year, over 17 million people die from cardiovascular dise-ases in the world, which is a third of the population dying (1,2).
Cardiovascular diseases include: ischemic heart disease (stable angina pectoris, acute coronary syndrome, sudden cardiac death, cardiac insufficiency), acute stroke (ischemic stroke and haemorrhagic stroke), and peripheral arterial occlusive disease.
According to World Health Organization (WHO) estimation, the dying structure from cardiovascular diseases is as follows: ischemic heart disease is on average 41%, stroke with 32% and other heart disease with 27% (3).In our country the situation is significantly different: slightly more than half of those who died of CV disease had a diagnosis of one of the heart diseases, while the participation of the stroke was 29% (4).
Coronary artery disease (coronary or ischemic heart disease) is the most common cause of death, leading to death, disability and economic losses more than any other illness, despite a significant reduction in mortality over the past three decades.The frequency of may be been seen from the results of large studies, according to which, the risk of the onset of coronary artery disease during life, for a man at the age of 40, is almost 40% (3).
The role of the surgeon in the process of CV disease treatment, finds its significant place from the moment when it came to the knowledge that obstructive atherosclerotic lesions on the coronary arteries are directly responsible for the onset of coronary disease.Aortocoronary bypass is a procedure that is carried out at the heart in order to overcome narrowing of blood vessels that nourish the heart.The results of the conducted research show that in the United States alone, 1 500 000 patients suffer from coronary heart disease annually, while surgical myocardial revascularization is performed in almost every fourth patient.A similar trend was observed in the countries of Western Europe (1,000 revascularization per million inhabitants), while in our country this number is significantly lower (600 revascularization per million inhabitants) (5).
Although surgical revascularization of the myocardium is now the most commonly performed surgical procedure in general, with mortality of about 1% in elective cases, there is still a high risk of emergency surgery in patients with acute coronary syndrome (6).Previous studies suggest that surgical revascularization of the myocardium has been a method of choice for the treatment of most patients with coronary heart disease for more than 50 years.The results of surgical treatment are superior in comparison with empirical medication therapy, in almost all investigated subgroups of patients.After performing this surgical procedure, a longer survival, longer period without new myocardial infarction, and significant improvement in the quality of life is achieved, while the incidence of the new chest pain onset is lower and the working capacity of the majority of operatives is excellent.It is therefore important to note that there are many benefits of early surgical revascularization, including limiting of infarction expansion, avoiding left ventricular dysfunction and cardiac insufficiency.The underlying risk lies in the ischemic-reperfusion myocardial damage, which can lead to the appearance of a hemorrhagic infarction, with all of its complications (5,7,8).

Material and methods
The aim of this study was to examine the correlation between mortality, bleeding and the need for transfusion, the length of hospitalization and the presence of postoperative complications (respiratory, renal and hepatic) in relation to parameters of coagulation and fibrinolysis activation, platelet function disorders and inflammatory parameters, in patients who underwent surgical myocardial revascularization.
According to the statistical tests and calculations in the G-Power software package, this study included 28 patients who underwent surgical myocardial revascularization at the Clinic for Cardiovascular with Transplantation Surgery KC Niš, in the period from January to April 2017, which is reduced the probability of α error to a level of significance r < 0.05 with a defined power of study of 80%.
The correlation of the above parameters with comparison to the duration of the extracorporeal circulation and the duration of the aortic cross clamp is determined.

Statistical analysis
Quantitative statistical analysis was carried out on a computer.Excel program from the Microsoft Office 2010 software package was used for typing, ranking, grouping, table and graphical data presentation.The calculations were made using the SPSS program in version 18.0.
The following statistical parameters were displayed: arithmetic mean (AS), standard deviation (SD) and structure index (%).
Comparison of mean values of numerical features between groups of patients with and without bleeding was performed by Student's T test or Man-Whitney U test, in cases where the distribution of values did not meet the requirements of normal schedule.Comparison of mean values of numerical features in the same patients between two measurements was done by the Paired-samples t test.
A comparison of the frequency of attributes between groups was performed by Mantel-Hensel's Quadratic Test (Mantel-Haenszel Chi square test) or Fisher exact test of the exact probability of a zero hypothesis (Fisher exact test) when one of the expected frequency of the mark was less than five.Changes in the value of the mark during the followup period were examined by Repeated measures ANOVA.
The study of the relationship between the amount of allogeneic transfusion, the number of days of total hospitalization, the number of days of hospitalization in intensive care, total drainage and all other investigated features was carried out by Spearman's rank correlation.
Determination of significant bleeding predictors was performed by multivariate logistic regression analysis.The odds ratio (OR) and the 95% confidence interval (CI) were calculated.By using the Wald method step-by-step (Backward: Wald) from a mul-tivariate model, all factors, the statistical significance of which, was not confirmed were excluded.
Multivariate linear regression analysis was used to determine factors significantly related to the values of allogeneic transfusion, the number of days of hospitalization overall, the number of days in intensive care and total drainage.The values of regression coefficients (B) and the limits of their 95% confidence interval were calculated.Using stepwise methods in final models, only those factors that are significantly related to dependent variables are retained.As a threshold of statistical significance in the conclusion, the estimation error was less than 5% (p < 0.05).The statistical analysis results were showed as tables and graphically.

Results
The study included 28 patients, 22 men (79%) and 6 women (21%), the average age of 64 years.The basic characteristics of the respondents are shown in Table 1.Allogeneic transfusion was administered in 3 patients on the first postoperative day, and the average blood amount was 933.3 ml (Table 2).On the second day it was applied in two patients, 350 ml each, the third day in one patient, 700 ml, the fourth day in 4 patients, 350 ml each.
On the fifth postoperative day allogeneic transfusion was not applied to any patient.On the sixth and seventh day, allogeneic transfusion was administered in 2 patients, in 350 ml each.In total, allogeneic transfusion was received by 12 patients, and the approximate amount of blood was 583 ml.
The drainage was measured for the first two days in all 28 patients, and the average value was 414.3 ml during the first day and 416.9 ml during the second day.On the third day, the drainage was measured in 18 patients, on average 190.8 ml, and on the fourth day in 3 patients on average 203.3 ml.After the fourth day, the drainage was not measured in any patient.
The diuresis was measured for the first three days in all 28 patients, and the average value was 2779 ml, 3004 ml and 2795 ml, by day.On the fourth day, the diuresis was measured in 17 patients, on average 2852 ml, on the fifth day in 9 patients on average 3105 ml, the six in 2 patients at 2850 ml, and on the seventh day in one patient, 1800 ml.
Platelets were administered only on the first day, in 4 patients with an average of 6.25 units, plasma, cryoprecipitate, volume and crystalloids were not applied.
The analysis of variance for repeated measurements showed that changes in the values of most of the features during monitoring were statistically significant (Table 3).
In almost all features, difference between preoperative values, values 2 hours after surgery and at the end of the follow-up period, was significant.In the period between 2 hours after the operation and at the end of the follow up period, the values of WBC, RBC, HGB and ACT decreased significantly, while the HCT  Comparison of values in patients with and without bleeding, within the examined groups is shown in Table 4.
Diabetes was significantly more commonly reported in patients without bleeding (Table 4).In patients without bleeding.,significantly higher BMI, triglycerides, cholesterol, ACT before surgery, PLT count preoperatively and INTEM ALPHA ANGLE were seen preoperativly, compare to patients with bleeding.In patients with bleeding, significantly higher values of the urea and difference in APTT preoperatively and at the end of the follow-up period, were detected compared to patients without bleeding.The values of all other features did not differ significantly in patients with and without bleeding.Multivariate logistic regression analysis, confirmed that the only factor significantly associated with the risk of bleeding, is a difference in APTT values preoperatively and at the end of the follow-up period (Table 5).An increase in this difference is associated with an increased risk of bleeding.
Variance analysis for repeated measurements showed that significant differences between the group of patients with and without bleeding existed at the PLT and ACT values over the entire period of follow-up ( Changes in ASPI values occurred in a significantly different way throughout the entire monitoring period in patients with and without bleeding. There were no significant effects of the group (bleeding) and the interaction between time and group in the overall monitoring period regarding the value of other parameters.
Multivariate linear regression analysis showed that the only factor significantly associated with the change in the total allogeneic transfusion value was the value of urea (Table 7).Increase in urea levels is associated with an increase in total allogeneic blood transfusion values (Graph 2).Multivariate linear regression analysis confirmed: the type of surgery (number of grafts), diuresis, ACT after AP, and an increase in HCT from preoperative period to period 2h after surgery, as factors significantly associated with changes in the number of days in intensive care (Table 8).
An increase in the number of grafts and diuresis is associated with an increase in the number of days in intensive care, while the rise in ACT after AP and HCT difference preoperatively and 2h after surgery, are associated with a decrease in the number of days in intensive care (Graph 3).
Multivariate linear regression analysis, confirmed the amount of cardioplegia, the difference in RBC values in the period of 2 hours after the operation to the end of the monitoring period, and the difference in values of PT and EXTEM CT in the period before surgery to the end monitoring period as factors sig-nificantly associated with changes in the number of days of total hospitalization (Table 9).
An increase in the amount of cardioplegia has been associated with a reduction in the number of days of total hospitalization, while an increase in RBC values in the period from 2 hours after operation to the end of the follow-up period, as well as an increase in the values of PT and EXTEM CT from the period before surgery to the end of the monitoring period, has been associated to increased number of days of total hospitalization.
Multivariate linear regression analysis, confirmed the preoperative value of INR as the only factor significantly associated with changes in total drainage value (Table 10).The increase in preoperative INR value is associated with an increase in the total drainage value (Graph 4).

Discussion
Cardiosurgical interventions carry a certain risk with them.This risk depends on age, gender, heart function, condition of the whole organism, urgency of the intervention, etc. Statistical analysis of a large number of cardio-surgical patients has determined the factors that influence the operational risk.
According to the National Blood Collection & Utilization Survey (NBCUS), blood transfusions and blood derivatives, with the exception of platelet transfusions, declined between 2008.and 2011. in the United States (9).In this period, a reduction rate of 8.2% of red blood cell transfusions (RBC) was recorded, as well as a reduction in plasma transfusion by 13.4%.In the United States, contrary to the general trend, there has been an increase in blood transfusions and blood derivatives during cardiovascular surgery during 2010, when a total of 34% of patients undergoing transfusion received red blood cells or other blood derivatives (10).Moreover, cardiac surgery was a branch of surgery that consumed the largest amounts of blood, just before orthopedic surgery (11,12).Transfusion is often necessary during cardiovascular surgery to cure coagulopathy, blood loss, and hemodilution due to priming (13).Very often, patients who undergo cardiac surgery have numerous comorbidities such as anemia or myocardial infarction, which increase the risk of complications, and therefore the need for blood transfusion is higher (10,11,14).
This study included a total of 28 patients who underwent surgical revascularization of the myocardium at the Clinic for Cardiovascular with Transplantation Surgery, Clinical Centre of Niš, 22 men (79%) and 6 women (21%), with average age of 64.The most common risk factor for these patients was diabetes mellitus, which was present in 46.4% of patients.In our study, there was 21.4% smokers fewer than in other published studies (13)(14).This study also showed that BMI was a significant indicator of the incidence of coronary disease, so the average BMI for examiners in our study was 29.94.
The most commonly performed procedure for these patients was double and triple aorto-coronary bypass, with 46.4% of patients having a double aorto-coronary bypass, and 42.9% of patients with triple aorto-coronary bypass.The average number of grafts that patients received was 2.57.
The average ECC time was 102 minutes and the time for the aortic cross clamp was 45 minutes, on average, 1158 ml of cardioplegia was given.
Allogeneic transfusion was administered in 3 patients on the first postoperative day, and the average blood amount was 933.3 ml.On the second day it was applied in two patients, 350 ml each, the third day in one patient, 700 ml, the fourth day in 4 patients, 350 ml each.
On the fifth postoperative day allogeneic transfusion was not applied to all patients.On the sixth and seventh day, allogeneic transfusion was administered in 2 patients, in 350 ml each.In total, allogeneic transfusion was received by 12 patients, and the approximate amount of blood delivered to them was 583 ml.
The diuresis was measured for the first three days in all 28 patients, and the average value was 2779 ml, 3004 ml and 2795 ml, by day.On the fourth day the diuresis was measured in 17 patients, on average 2852 ml, on the fifth day in 9 patients on average 3105 ml, the six in 2 patients at 2850 ml, and on the seventh day in one patient 1800 ml.
Platelets were administered only on the first day, in 4 patients with an average of 6.25 units, plasma, cryoprecipitate, volume, and crystalloids were not applied.
Several studies published the results and effects of blood transfusion in anemic and non-anemic, haemodynamically stable patients.(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).A retrospective study carried out in Cleveland Clinic showed that patients undergoing cardio-pulmonary bypass and who did not have anemia during the ECC procedure (hematocrit > 25%), but who received an intraoperative blood, had a need for longer use of mechanical ventilation and they had reduced longterm survival compared to a non-anemic group of patients or with patients who had anemia but did not receive blood (27).Blood transfusions in patients un-dergoing surgical myocardial revascularization, who were preoperatively classified in a group with a low or moderate risk according to EuroSCORE (< 8) and who had a postoperative hemoglobin greater than 10 g / dL and a minimum postoperative blood loss and without postoperative complications in the first 24 hours of surgery, caused an increased risk of postoperative events and infections in relation to those patients who did not receive blood replacement (17,(21)(22)(23)28).
Shaw et al. compared the effects of blood transfusion in a group of patients who were stratified by the value of hematocrit.Preoperative hematocrit values were compared in patients undergoing cardiac surgery depending on whether they received blood transfusion or not (29).This study showed a statistically significantly higher rate of mortality after 30 days, for that group of patients who received blood transfusion compared to a group of patients who did not receive blood.These results are in agreement with previously published studies that confirm that there is a higher mortality rate in patients receiving blood transfusion (28,(30)(31)(32)(33).
A retrospective study published by Schwann et al. investigated the correlation between blood transfusion and mortality in 6,947 patients who underwent surgical myocardial revascularization (34).The overall rate of the red blood cells transfusions was 33.9%.Postoperative complications were present in 35.2% of patients, and this was statistically significantly higher in comparison to a group of patients who did not receive blood transfusion.The most common complications of this type were present in older women with comorbidities.Early mortality (30 days after surgery) and five-year survival were higher among the group of patients receiving blood transfusion, compared to those who did not receive red blood cells.The authors concluded that red blood cell transfusion increased the risk of cardiac and noncardiac mortality in patients who underwent surgical myocardial revascularization (34)(35)(36).
The initial decline after the operation, with a subsequent increase at the end of the monitoring period, was recorded for values of RBC, HGB, PLT, AT III, EXTEM MCF, EXTEM A10, EXTEM ALPHA ANGLE, INTEM MCF, INTEM A10, INTEM ALPHA ANGLE, FIBTEM MCF, FIBTEM A10 , FIBTEM ALPHA ANGLE and ACT.
The initial increase after surgery, with subsequent decline at the end of the monitoring period, was recorded for the values of WBC, CRP, fibrinogen, INTEM CT, troponins and CK MB.
The increasing trend during the entire monitoring period was recorded for values of P SEP, D dimer, ADP HS, ASPI, TRAP and FIBTEM CT.
In relation to preoperative values, the number of WBC significantly increased 2 hours after surgery, while the values of RBC, HGB, HCT, and PLT significantly dropped in the same period.
Diabetes was significantly more common in patients without bleeding.In patients without bleeding, significantly more BMI, triglyceride, cholesterol, preoperative ACT, PLT and INTEM ALPHA ANGLE were preoperatively detected, compare to patients with bleeding.
In patients with bleeding, significantly higher values of the urea and APTT difference preoperatively and at the end of the follow-up period were detected compared to patients without bleeding.The values of all other parameters did not differ significantly in patients with and without bleeding.
The multivariate logistic regression analysis, confirmed that the only factor significantly associated with the risk of bleeding, is a difference in APTT values preoperatively and at the end of the follow-up period.An increase in this difference is associated with an increased risk of bleeding.
The variance analysis for repeated measurements showed that significant differences between the group of patients with and without bleeding existed at the PLT and ACT values.
The changes in ASPI values occurred in a significantly different way throughout the entire monitoring period in patients with and without bleeding.
There were no significant effects of the group (bleeding) and the interaction between time and group in the overall monitoring period, in the value of other features.
The correlation analysis showed that the increased values of total allogeneic transfusion were significantly associated with elevated urea values and increased differences in APTT and CK MB values preoperatively and at the end of the follow-up period.
The multivariate linear regression analysis confirmed the value of urea as the only factor significantly associated with the change in the total allogeneic transfusion value.The increase in urea levels is associated with an increase in the total amount of allogeneic transfusion.
The correlation analysis showed that the increased number of days in intensive care was significantly associated with female gender, higher number of grafts, prolonged ECC time, aortic cross clamp time, diuresis, AT III preoperative, EXTEM CT preoperatively, increased differences in HCT, PT, INR preoperatively and at the end of the monitoring period.
An increased number of total hospitalization days was significantly associated with lowered values of given cardioplegia and PLT preoperative values with declines in WBC and HGB values in the period before surgery to 2 hours after surgery, as well as with the decline in troponine levels in the period before surgery to the end of the follow-up period.
The multivariate linear regression analysis confirmed the amount of cardioplegia, the difference in RBC values in the period of 2 hours after the operation to the end of the monitoring period, and the difference in values of PT and EXTEM CT in the period before surgery to the end of monitoring period as factors significantly associated with changes in the number of days of total hospitalization.
An increase in the amount of cardioplegia has been associated with a reduction in the number of days of the hospitalization, while an increase in RBC values in the period of 2 hours after operation to the end of the follow-up period, as well as an increase in the values of PT and EXTEM CT in the period before surgery to the end of the monitoring period, has been associated with increased number of hospitalization days overall.
The correlation analysis showed that an increase in the total drainage value was significantly associated with an increase in triglyceride and preoperative HCT values, while the increase in total drainage value was significantly associated with a fall in preoperative INR.The multivariate linear regression analysis confirmed the preoperative value of INR as the only factor significantly associated with changes in total drainage value.The increase in preoperative INR value is associated with an increase in the total drainage value.A major dilemma in bleeding patients is whether coagulopathy or mechanical bleeding is the cause of the increase drainage and whether it is necessary to continue with the administration of hemostasic therapy and blood products or perform revision in the operating room.In less than ten minutes, ROTEM test guide doctors in which direction they should work.
The number of transfused allogeneic blood products is declining year after year, which points to the importance of modern monitoring in the indication of blood transfusions by the doctors.Transfusion of fresh plasma is also reduced.Transfusion of concentrated platelets remained at the same level, but percentage of cryoprecipitate transfusions increased year after year (37).
Despite improvements made with existing new techniques, most surgeons tend to accept a significant amount of blood loss as a feature of cardiac surgery (38).It is important to ensure adequate drainage and removal of blood from pericardium and pleura (it has high fibrinolytic activity and tissue factor of coagulation).Removing this blood and clot probably not only reduces the chance of excessive blood loss by preventing systemic coagulopathy, but it is likely to have beneficial effects on several other factors associated with surgery such as, for example, inflammation, atrial fibrillation, pericardial effusion (tamponade), and development of the adhesions (39).After careful evaluation, hemodilution appears to be the most pronounced factor associated with the development of coagulopathy after cardiac surgery, and probably plays an important role in the occurrence of blood loss after heart surgery (40).Fibrinogen is one of the most important factors in coagulation and it is possible that the clotting process falls below the critical level during hemodilution and therefore care should be taken and, if necessary administration of fibrinogen concentrate initiated (41).
Fibrinogen is an acute phase protein the level of which gradually increases during and after surgery in response to a surgical trauma and the use of ECC.The increased concentration of D-dimer and prothrombin fragment 1 + 2 together with increased thrombin production indicate that the hypercoagulable state develops up to 5 days after cardiac surgery.The combination of these two factors (hypercoagulable state and the use of fibrinogen concentrates) can increase the risk of thromboembolic complications in the postoperative period.Therefore, adequate anticoagulant and (or) antiaggregation therapy to prevent the occurrence of thromboembolic complications in the postoperative course is necessary, especially in patients who do not receive vitamin K antagonists, even in patients without prior bleeding.A delicate balance between bleeding and hypercoagulable states must be maintained.The use of POC evaluation can provide a quicker and more complete insight into this delicate balance, creating more individualized treatment oriented to each patient in particular.A large variation in the patient's sensitivity to the use of clopidogrel often results in very different individual results before surgery, which requires further use and determination of the POC before, during and after cardiac surgery.An individual approach oriented to each patient can contribute to the reduction of perioperative and postoperative blood loss and minimizes the need for transfusion to a minimum (42).
Transfusion of red blood cells is common in cardiac surgery.The percentage of patients receiving blood transfusion during the perioperative period varies in literature: from 95%, up to 10 years ago, to 49% of CABG patients over the past few years.Blood transfusion can improve systemic transport and distribution of oxygen, relieve regulation of vasomotor response, improve delivery of oxygen to the myocardium.On the other hand, there are data in the literature that indicate that transfusion damage is probably more serious than it has been valued so far and that blood transfusions are used more often than necessary (43).Even transfusion of one blood unit is associated with a significant risk of serious postoperative morbidity, the immediate goal should be to avoid transfusion whenever possible and not to apply it just to treat low hemoglobin levels, which is a common practice in over 50% of all patients receiving transfusion.Traditional concern over transfusion of blood and blood derivatives is reduced to the possibility of transmitting viral and bacterial infections or the occurrence of haemolytic reactions, which is rarely occurring.However, immunosuppression, lung damage, or dysfunction of the organs can occur with each recipient.Recently, Cleveland Clinic investigators have found that the administration of erythrocytes that have been stored for a longer period (> 14 days) is independently associated with an increased risk of complications and increases the estimated risk of death (30).This happens because the erythrocytes over time develop lesions and release cytokines, cell membranes fragment and release hemoglobin and free oxygen radicals.Obviously, there is a challenge to determine the circumstances in which transfusion is used.Unfortunately, the existing evidence is scarce, and the existing guidelines and recommendations are based on a low level of evidence.Assuring doctors to change their practice is not an easy task and an appropriate clinical assessment is used as a justification for transfusion.
Numerous strategies exist to minimize the need for a transfusion of blood and blood products in the perioperative period.Some of the existing guidelines recommend: discontinuation of preoperative application of antithrombotic drugs, applying a restrictive attitude about the level of hemoglobin requiring red blood cell transfusion, the application of intraoperative blood savage techniques, and offpump CABG as one of the of surgical techniques that can reduce bleeding in the postoperative course.The study we conducted showed that using the POC and Rotem methods in the preoperative and postoperative period, can reduce postoperative bleeding to an acceptable level that in most patients does not require the use of blood and blood derivative transfusion.Antiagregation therapy was stopped before surgery and was re-administered after taking drains out.Reinfusion of the remaining blood at the end of the CPB and the use of the Cell Saver system were applied to all patients involved in our study.But perhaps most importantly, doctors should be encouraged to use a restrictive hemoglobin compensation model, which is also recommended in special guidelines: patients should be given blood transfusions when hemoglobin is less than 7 g / dL, where transfusion is not indicated for improving oxygen transport and when the hemoglobin concentration was higher than 10 g / dL.About 20% of all CABG operations are in off-pump technique.The use of CPB during CABG is associated with more harmful effects, including hemodilution, activation of coagulation factors, and a decrease in the number and function of platelets, leading to coagulopathy that can lead to extensive bleeding and the need for massive blood transfusions.Because of this, off-pump procedures would be expected to lead to a reduction in the incidence of postoperative complications, and are also recommended to reduce the need for transfusion.However, in our study, did not notice the significant differences between individual patient groups in whom increased bleeding could be expected in the intra and postoperative period.The number of platelets and their function was tracked at 8 different time points.Our study did not show that there was statistically significant correlation between individual groups of patients compared to basic biochemical and inflammatory parameters with the number and function of platelets.There has been a decrease in platelet counts intraoperatively, and a gradual increase in their number in the immediate postoperative period.Increased perioperative bleeding was associated only with a reduced number and platelet function as well as elevated ACT rates.
The only parameter in our study that was associated with increased postoperative drainage was increased preoperative value of INR.In our study, only 4 patients (14.28%) received platelets while 12 patients received a blood supply (42%), an average of 583 ml.We didn't have any reintervention because of bleeding.Our study could not show independent prognostic factors of greater postoperative drainage compared to the classic operational parameters that are being monitored (aortic cross-clamp and ECC time...), nor in relation to the parameters of inflammation.

Conclusion
Based on the conducted research and the obtained results, it can be concluded: -Surgical myocardial revascularization is a safe technique with a minimum morbidity rate.
-By using of modern methods for preoperative hemostasis monitoring (Multiplate, Rotem), the risk of postoperative bleeding can be significantly reduced, as well as the need for transfusion of red blood cells and other blood derivatives.
-The only preoperative independent prognostic parameter for increased postoperative drainage was INR.
-ACT was an independent postoperative prognostic parameter of increased postoperative drainage, probably due to delayed or prolonged heparin activity -Inflammation parameters did not show association with the occurrence of postoperative complications.
-Diabetes was significantly more common in patients without bleeding.The same conclusion was for patients with higher BMI.
-In patients with bleeding significantly higher values of urea and the difference in APTT preoperatively and at the end of the follow-up period were detected compared to patients without bleeding.
-Multivariate logistic regression analysis confirmed the difference in APTT values preoperatively and at the end of the monitoring period, as the only factor significantly associated with the risk of bleeding.
-Correlation analysis showed that the increased values of total allogeneic transfusion were significantly associated with the elevated values of urea and increased differences in APTT and CK MB values preoperatively and at the end of the follow-up period.
-Multivariate linear regression analysis confirmed the urea value as the only factor significantly associated with the change in the total transfusion value.The increase in urea levels is associated with the increase in the total amount of allogeneic transfusion.
-The correlation analysis showed that the increased number of days in the intensive care was significantly associated with female gender, high number of grafts and prolonged ECC and aortic cross -clamp time, HCT, PT, and INR values preoperatively and at the end of the follow-up period. .

Table 1 .
The basic characteristics of the respondents

Table 2 .
Application of allogeneic transfusion, blood derivatives, voluven and crystalloids, drainage and diuresis per follow-up days

Table 3 .
Values of the blood count, inflammation parameters, coagulation status, platlets, rotational thrombelastometry, internal and external coagulation pathway

Parameter Preoperatively 2 hours after Surgery 24 hours after surgery 48 hours after surgery 72 hours after surgery 5 days after surgery 7 days after surgery Effect time WBC
NOTE: values are displayed as arithmetic mean ± SD

Table 4 .
Comparison of values in patients with and without bleeding

Table 5 .
Association of the investigated parametres and risk for bleeding, results of multivariate logistic regression analysis

Table 6 .
Evaluation of the effects of the group (bleeding) and interaction between time and group on the values of individual parameters during the entire monitoring period, results of variance analysis for repeated measurements (RM ANOVA) Graph 1. PLT, ACT, and ASPI values in patients with and without bleeding

Table 7 .
Connection betweenl total allogeneic transfusion and values of other investigated features, results of multivariate linear regression analysis The relationship between the value of total allogeneic transfusion amount and urea values

Table 8 .
The relationship between the number of days in intensive care and the value of all other investigated features, the results of the multivariate linear regression analysis UreaGraph 3. The relationship between the number of days in intensive care and the number of grafts, ACT after AP, HCT difference preoperatively and 2h after surgery and diuresis

Table 9 .
The relationship between the number of days of total hospitalization and the value of all other investigated features, the results of multivariate linear regression analysis

Table 10 .
The relationship between the total drainage value and the value of all other investigated features, the results of the multivariate linear regression analysis The relationship between total drainage and preoperative value of INR