Outcome of Plasma Fibrinogen Level and Postoperative Bleeding Following OPCAB Surgical Patients

Introduction

Coronary artery disease (CAD) is one of the most scrutinized diseases in medical science and coronary revascularization is the most studied intervention. Coronary artery disease (CAD) results from narrowing of the coronary arteries. The narrowing is caused by thickening and loss of elasticity of arterial walls. When this nar- rowing is sufficiently severe, it limits blood flow to the myocardi- um. At primary stage, the disease limits only coronary flow reserve (increase inflow that normally accompanies increased myocardial oxygen demands) but when sufficiently advanced, CAD reduces blood flow through the affected artery even at rest. In its most se- vere form, atherosclerotic CAD occludes the coronary artery [1]. Initially, for revascularization of the coronary arteries in CAD, coronary artery bypass surgeries were performed using cardiopul- monary bypass with cardioplegic arrest [2]. To reduce postoper- ative complications caused by systemic inflammation, off-pump coronary artery bypass (OPCAB) was introduced into clinical practice in the early 1990s [3]. During off-pump surgery, the coro- nary artery grafts are placed on coronary arteries of a beating heart using intra-coronary shunts, thereby avoiding aortic cross clamp- ing and CPB. Benefits of OPCAB are early extubation, reduced perioperative blood transfusion, hospital stay and mortality [4]. In spite of having several advantages, OPCAB is still accompanied with a risk of complications such as bleeding, infections, stroke, and myocardial infarction with heart failure, renal insufficiency and pulmonary dysfunction [5]. Bleeding is a common and severe complication after cardiac surgery. It may be caused by surgical factors or disturbed hemostasis or combination of both. Disturbed postoperative hemostasis may be related to impaired coagulation, increased fibrinolysis or platelet dysfunction [6]. Fibrinogen is a key protein in hemostasis synthesized by the liver. It is also known as clotting factor I (one) and it circulates in plasma at a concen- tration of 2.0-4.5 gm/L. In healthy human adults, about 2-5 gm of fibrinogen is synthesized daily and the same amount is catab- olized. The plasma half-life of fibrinogen in normal humans has been estimated to be 3-5 days. Fibrinogen is converted in plasma by thrombin into fibrin, which under the influence of factor XIII is formed into a meshwork at the site of tissue damage to minimize blood loss and stimulate tissue repair. Fibrinogen is the final clot- ting factor activated in the coagulation cascade during hemostasis [7]. Fibrinogen binds to the specific platelet receptor, which is im- portant for incorporating platelet aggregation [8]. Thus, in primary hemostasis it supports formation of platelet plug and in secondary hemostasis the formation of insoluble fibrin clot. Fibrinogen and fibrin also interact with other adhesive glycoproteins, hemostatic factors and blood cells forming a complex system that constitutes the process of hemostasis. Therapeutic fibrinogen substitution is based on products derived from human plasma, such as fresh-fro- zen plasma (about 2-3 mg/ml), cryoprecipitate (about 200-250 mg/unit) or fibrinogen concentrate (dose: 70mg/kg body weight). However, there were significant inverse correlation between post- operative bleeding and preoperative fibrinogen levels [9].

Objective

To find out Outcome of Plasma Fibrinogen Level and Postopera- tive Bleeding Following OPCAB Surgical Patients.

Material and Method

This comparative cross-sectional study was carried out at the De- partment of Cardiac Surgery in BSMMU hospital from March, 2017 to August, 2019. The study population was 60, with 2 (two) groups having 30 patients in each. Patients from both the groups underwent OPCAB. Statistical analysis of different characteristics between the patients of both groups was done to draw a conclu- sion.

Data Collection

All patients admitted in Cardiac Surgery Department, BSMMU with coronary artery disease scheduled for OPCAB were consid- ered as study population (without exclusion criteria). Patient who fulfilled the inclusion criteria and willing to enroll in the study was included in the study after receiving the proper consent. The spec- imen was platelet-free plasma or platelet poor plasma. Amount of specimen needed from each subject is 1 ml of plasma. To obtain this, after all aseptic precaution, venous blood sample was col- lected from each study subject in a disposable plastic syringe and immediately transferred to a sterile 2.7 ml blue-top (3.2% sodium citrate) tube. Then, the tube was gently moved upside down for several times to mix the whole blood with 3.2% sodium citrate. Blood was not drawn from a heparinized line. To avoid contam- ination of the sample with tissue thromboplastin or heparin, ve- nipuncture was done very carefully to avoid any trauma. In case blood was drawn from an indwelling catheter, it was flushed with 5 ml of saline and the first 5 ml of blood collected was discarded. If drawn with a butterfly setup, a discard was made first to remove air from tubing. Tubes were labeled with patients name, ID num- ber & collection date and sent to BSMMU Hematology laboratory immediately for centrifugation & further procedure. Standard an- esthetic techniques of induction and maintenance were followed for all procedures.

Data Analysis

Statistical analysis was conducted using Statistical Package for Social Science (SPSS) version 23.0 for windows software. Com- parisons between groups were made with Student’s t-test, Chi- Square test and Fisher’s exact test. The results were presented in tables. Observations were recorded as statistically significant if a p-value is ≤0.05.

Results

This study total sixty (60) patients who underwent off-pump coro- nary artery bypass graft surgery were evaluated in this study. Post- operative care at ICU was given to the patients of both groups as per standard hospital protocol. The findings of the study obtained from data analysis presented in the following pages.

Comparison of demographic and anthropometric variables:

Among the study population mean age in group A was 55.43±8.53 years and in group B was 59.63±6.86 years. The difference in age between two groups was statistically significant (p<0.05). There was no statistical significance of gender between the two study groups (p>0.05). The mean BMI in group A was 24.13±2.49 kg/ m² and that in group B was 24.62±3.71 kg/m². The findings were statistically not significant (p>0.05) [Table-1].

Table 1: Comparison of demographic and anthropometric variables: (N=60)

Table in the parentheses indicate percentage. Data were analyzed using, aStudent’s t-test and was presented as mean ± SD. bChi- square test (χ2) was used to measure the level of significance. *p>0.05 was considered not to be significant. n= number of sub- jects, s= significant, ns= not significant, BMI = Body Mass Index.

Comparison of postoperative variables regarding blood loss:

Table 2 shows the comparison of postoperative variables between group A and B patients. Amount blood loss in 1st 12 hours imme- diate after surgery in group A and B were 185.67±35.20 ml and 219.67±57.32 ml respectively, which was statistically significant (p<0.05). Amount blood loss in 1st 24 hours after surgery in group A and B were 306.00±73.37 ml and 370.33±69.65 ml respective- ly, which was also statistically significant (p<0.05). Total drain collection after surgery in group A was 792.33±160.32 and in group B was 905.33±137.03 ml, which was statistically significant (p<0.05).

Table 2: Comparison of postoperative variables regarding blood loss: (N=60)

Data were analyzed using, Student’s t-test and was presented as mean ± SD. *p>0.05 was considered not to be significant. n= num- ber of subjects, s= significant.

Comparison of postoperative outcome variables:

Table 3 shows that among the study population, difference between the postoperative ventilation time of the two groups was not sta- tistically significant (p>0.05). Post-operative blood transfusion in group A and B were 2±0.53 units and 2.5±0.68 units respectively, which was statistically significant (p<0.05). Duration of ICU stay following surgery was longer in group B patients (64.37±11.98 hours) compared to group A patients (58.5±9.06 hours), which was statistically significant (p<0.05). Difference between the duration of hospital stay of the two groups was also statistically significant (p<0.05).

Table 3: Comparison of postoperative outcome variables: (N=60)

Data were analyzed using, Student’s t-test and was presented as mean ± SD. *p>0.05 was considered not to be significant. n= num- ber of subjects, s= significant, ns= not significant, ICU=Intensive Care Unit.

Discussion

The study was conducted at BSMMU hospital, Shahbagh, Dha- ka, Bangladesh included a total number of 60 patients undergo ing OPCAB as per the inclusion and exclusion criteria. The pa- tients were divided into two groups (Group A and Group B; 30 patients in each). Alagha and associates found a clear threshold for the plasma fibrinogen level postoperative bleeding following OPCAB of 3.1gm/L. OPCAB was performed and postoperative ICU care was given to the patients of both groups as per stan- dard protocol. The demographic variables of the participating pa- tients were recorded and analyzed. The mean age for group A was 55.43±8.53 years and group B was 59.63±6.86 years respective- ly, the difference was statistically significant (p=0.012). The age range of the patients of this study was from 42 years to 72 years. This study observed that the incidence of low plasma fibrinogen and postoperative bleeding were more common in old age. A sim- ilar study showed plasma fibrinogen level and relation to age was statistically significant (p=0.015) which was carried out by Ucar and colleagues [10]. In group A, approximately two third of the population were male 23 (76.66%) and one third 07 (23.33%) were female. In group B, Male were 18 (60%) and 12 (40%) respec- tively. Male patients were predominant in both the groups. The distribution of gender between the groups were not statistically significant (p=0.16). Ucar and associates also found insignificant (p=0.87) relationship between fibrinogen and gender (male gen- der=400.7±123.0 versus female gender=395.6±148.1) [10]. A study done by Blome and colleagues in 2005 included ninety-eight (n=98) patients undergoing CABG showed that sex distribution had no significant influence (p=0.389) on postoperative bleeding [11]. When average BMI was compared between the two groups, it was 24.13±2.49 kg/m2 in Group A and 24.62±3.71 kg/m2 in Group B. The difference was statistically insignificant (p=0.548). This finding correlates to this study of Kim and colleagues, where they found BMI distribution among the groups was not significant (p=0.096) [12]. Presence of diabetes mellitus as a risk factor be- tween two groups were also analyzed statistically but was found to be of no significance (p=0.121). Alagha and associates found distribution of diabetic patients between the two groups were not statistically significant as a risk factor (p=0.07) [10]. Distribution of hypertensive patients between group A and group B was ana- lyzed. Group A had 20 (66.7%) hypertensive patients and group B had 19 (63.3%). This distribution was not statistically significant (p=0.787). The finding of Kim and colleagues correlates with cur- rent study, in which p=0.058 for hypertension [12]. In this study, Group A had 03(10%) patients of COPD whereas group B was comprised of 04(13.33%) COPD patients. In that study, the mean platelet count of two groups were 264±90 ×103/cumm of blood and 240±85 ×103/cumm of blood respectively which was statis- tically significant (p<0.001) [11]. In current study it was found that, the mean PT of the two groups were 12.29±0.68 seconds and 12.34±0.65 seconds with mean APTT of group A 33.83±3.02 sec- onds and group B 33.17±2.70 seconds. No significant association was found between PT (p=0.758) and post-operative bleeding. The association of APTT was also statistically insignificant (p=0.371). These findings also correlate with the findings of Blome and Col- leagues [13]. The difference in ACT after heparinization and ACT after heparin neutralization between the two groups was statis- tically not significant (p>0.05). Mean ACT after Heparinization was 357.9±31.26 seconds in group A and 389.1±26.86 seconds in group B (p=0.142). The average ACT after Heparin neutralization in both groups were 123.27±9.17 seconds and 129.47±8.24 sec- onds (p=0.332). Similar findings were observed in the study done by Rosin and Holt [13]. Operative time to perform OPCAB on patients of group A and B were also compared statistically. The mean time taken to complete OPCAB in group A was 4.38±0.57 hours and that of group B was 4.53±0.66 hours, which was statis- tically not significant (p=0.347). Comparison of number of distal grafts performed on patients of group A and B was also not sig- nificant (p=0.324). These findings correspond to the study con- ducted by Jeppsson and associates [12]. In present study, mean blood loss in 1st 12 hours in group A was 185.67±35.20 ml and 219.67±57.32 ml in group B and the difference was statistically significant (p=0.008). And the difference between mean Blood loss in 1st 24 hours in the two groups was (306±73.37 ml in group A and 370.33±69.65 ml in group B, range 180-550 ml) statisti- cally significant (p=0.001). These findings are also found in the retrospective study done by Alagha and associates. The difference of postoperative bleeding in 1st 24 hours following OPCAB was statistically significant (p=0.01) [11]. In the study done by Ucar [11], and associates, chest drainage was a mean of 972 ml (range, 240-2445 ml) and there were negative linear relation between the fibrinogen levels and the postoperative bleeding. This relation was statistically significant (r = –0.897, p<0.001) which correlates with current study [11]. The mean post-operative blood transfusion in group A and B were 2±0.53 units and 2.5±0.68 units respective- ly, which was statistically significant (p<0.05). These findings correspond to the study conducted by Tettey and associates [14]. The distribution of mean postoperative ventilation time in the two groups was not significant (p=0.181). This is comparable to the study conducted by Birla and associates [15]. The mean ICU stay of the patients of group A and group B (58.5±9.06 hours and 64.37±11.98 hours respectively) was observed and longer duration of ICU stay of the group B patients were statistically significant (p=0.037). This finding is similar to the finding (p=0.023) of Kim and colleagues. A logistic regression analysis was done to assess the predictive value of plasma fibrinogen level, age, platelet count for postoperative bleeding following OPCAB. Among the other variables plasma fibrinogen level was the most valuable predictor of postoperative bleeding following OPCAB (OR 2.960, 95% CI, 1.009-8.678, p=0.048). This is similar to the information provided by Alagha and associates [10]. There were no postoperative throm- boembolic events, cardiac ischemic incidents, re-exploration and mortality in present study.

Conclusion

In conclusion the efficacy were no postoperative thromboembol- ic events, cardiac ischemic incidents, re-exploration and mortali- ty. Fibrinogen concentration level was associated with increased postoperative bleeding in patients undergoing off-pump coronary artery bypass grafting surgical patients. Plasma fibrinogen level appears to be a useful predictor of postoperative bleeding in pa- tients undergoing OPCAB. Its preoperative level may indicate us to take necessary steps to prevent postoperative bleeding as well as reduce the rate of ICU stay. This study demonstrated fibrinogen levels are associated with increased postoperative bleeding follow- ing OPCAB fibrinogen determination may be a useful screening tool to identify individuals at added risk for excessive bleeding after OPCAB [16].

References