Introduction
Platelets are strongly affected by cardiopulmonary bypass (CPB) using a pumpoxygenator (1). Hypothermia, anticoagulant administration and hemorrhage are many of the other risk factors for thrombocytopenia (TP) after cardiac surgery (2). Even among patients undergoing off-pump coronary artery bypass surgery, evidence of platelet dysfunction or lower platelet counts after surgical intervention were also noted (3). The incidence of TP is about 35% among high-risk surgical patients and it reaches to 65% among cardiac surgery patients (4). Herein we aimed to investigate the clinical and prognostic value of early TP after cardiac surgery.
Materials and Methods
Design of the Study
The patients who underwent cardiac surgery electively in six-months period between February and August 2013, in our institute were enrolled to this cross sectional study. The blood samples were obtained from the patients at 12th, 36th and 60th hours postoperatively according to our daily practice. The patients who had platelet count under 150,000/μL were enrolled to TP group. The control group were selected randomly as the same number of patients with TP group among the patients with normal platelet count. The complete blood cell analyses were performed with the same machine for all samples. The variables were compared between the TP and control groups. Exclusion criteria were preoperative TP, any disease which may lead to TP such as malignancy, age under 18 and urgent operations. The antiplatelet therapy was discontinued five days before surgery.
The study was approved by the local Ethics Commitee (TUTF-GOKAEK 2013/21).
Surgical Technique
All patients were operated via a median sternotomy incision under general anesthesia and underwent CPB procedure. In routine, the left internal thoracic artery was preferred for revascularization of the left anterior descending artery, double clamp technique was used for proximal anastomosis and normothermic cardiac arrest was applied among the coronary artery bypass graft (CABG) surgery patients whereas mild hypothermic (32-34 oC) and moderate hypothermic (28-32 oC) cardiac arrest was applied in valve replacement and aortic procedures respectively. Mechanical prosthesis were used for valve replacement.
Postoperative Evaluation
TP was defined as a platelet count <150,000/μL and was classified as mild (i.e. 100,000/μL to 149,000 /μL), moderate (i.e. 50,000/μL to 99,999/μL) and severe (i.e. <50,000/μL) (4-8). The patients were evaluated postoperatively according to the Sequential Organ Failure Assesment (SOFA) as a prognostic scoring system (9). 4Ts scoring test was performed to evaluate heparin induced TP (HIT) (4,10). The platelet replacement was administered postoperatively to the patients with excessive drainage and TP with platelet count under 100,000/μL (2). Informed consent was obtained from all individual participants included in the study.
Statistical Analysis
Statistical analysis was performed by using a Statistical Package For Social Sciences (SPSS) version 21. Once tested for the normality of distrubition of continuous variables by one sample Kolmogorov-Smirnov test, a t-test was applied following normal distrubition and Mann-Whitney U test was done for comparing the data with no specific distribution. Categorical variables were analyzed through Pearson χ2 test, Fisher’s exact χ2 test and Kolmogorov-Smirnov two sample test. Descriptive data were defined as median (minimum-maximum) and arithmetic mean ± standard deviation. For all statistical tests p-values <0.05 were considered to be significant.
Results
Of 118 patients who were operated electively between February 2013 and August 2013 in our department, 39 developed TP (33.05%). Among the rest of the patients, 39 were randomly selected for control group. A total of 78 patients were enrolled to this study. Of 78 patients included in the study, 62.8% (n=49) were male and 37.2% (n=29) were female. The mean age was 61.82 (26-80). The mean platelet count was 115,580/μL (38,000-140,000/μL) among TP group. When the TP group was classified, 30 patients had mild (i.e. 100,000/μL to 149,000/μL), 7 patients had moderate (i.e. 50,000/μL to 99,999/μL), and 2 patients had severe (i.e. <50,000/μL) TP. None of the patients had score above low probability according to the 4Ts score.
The operations performed are reported on Table 1.
The preoperative and demographic data were not significantly different between the two groups.
The duration of CPB time was 112.58±43.39 minutes and 92.46±26.48 minutes (p=0.052) whereas the aortic cross-clamping time was 66.08±31.29 minutes and 50.59±19.37 minutes in TP and control groups respectively (p=0.034) (Figure 1). There was no significant difference between the two groups when we compared the hypothermia level, the volume of cardioplegic solution and the amount of heparine and protamine doses administered. The mediastinal drainage was increased in TP group (p=0.002) (Table 2). The unit of replaced fresh frozen plasma was significantly higher in TP group (p=0.001) (Figure 2).
SOFA scores were not significantly different between the groups at 12th hour whereas the 24th and the 48th hour scores were higher in TP group (p=0.137; p=0.001; p=0.001 respectively) (Figure 3).
The infection rates were increased in TP group (p=0.005) non-referred to the origin. The pulmonary (paO2/FiO2<200) and renal (creatinin >1.8 mg/dL or urine output <1000 mL/day) dysfunction rates were higher in TP group (p=0.006, p=0.038 respectively).
Reexploration for hemorrhage was 2.6% in control group and 10.3% in TP group (p=0.358). The length of stay for hospital and intensive care unit were increased in TP group (respectively p=0.006; p=0.030) (Figure 4). All in hospital mortality rate was 2.6% in control group whereas it was 12.8% in TP group (p=0.200).
Discussion
TP after CPB was reported to be associated with increased postoperative mortality, infection, stroke rates and prolonged intensive care unit and hospital length of stay (8). Herein we investigated that the infection rates were increased in TP group, non-referred to the origin (p=0.005). Beside of an important role in hemostasis, platelets also play a relevant function in inflammation acting as proinflammatory cells (11). TP occurs in over 50% of patients with septic shock (12). Platelet mitochondrial membrane depolarization reflects disease severity in patients with sepsis and correlates with clinical outcome (13). Serial platelet monitoring may help identify patients at higher risk of postoperative complications such as infections.
In our findings pulmonary dysfunction was more often in TP group (p=0,006). TP is associated with an increased risk of acute respiratory distress syndrome (ARDS) and platelet count in combination with ARDS had a high predictive value for patient mortality (14). The pulmonary vasculature likely offers ideal shear and turbulence to promote individual platelet shedding from megakaryocytes and proplatelets (15). Accordingly the high TP incidence may be considered as related with respiratory failure in our study. The renal dysfunction rate was also higher in TP group (p=0.038) in our study. Platelet activation and leukocyte inflammatory responses are important mediators of vascular microthrombosis and ischemic injury (16). The hemostatic balance during and after surgery may shift toward a hypercoagulable state and contribute to acute organ failure. The multiorgan failure concomitant with TP may be associated with the underappreciated microthrombosis after cardiac surgery (16). The limited use of perioperative antiplatelet therapy because of a culture of fear of bleeding, may be considered to be responsible for the issue (16).
TP is reported to reflect a physiologic imbalance and is accepted as an independent risk factor for poor outcome in patients who were supported with extracorporeal membrane oxygenation after cardiac surgery (17). Zhong et al. (18) developed a promising software model to realize and improve prognosis in ICU after open heart surgery. Patients who underwent coronary artery bypass surgery, aortic valve replacement, or other heart-related surgeries between 2001 and 2012 were analyzed and platelet count appeared to be an important predictor for outcomes (18). Early predicting comorbidities for critically ill patients after cardiac surgery is vital for patients’ prognosis and doctors’ decision making (18).
In our findings the mediastinal drainage (p=0.002) and the unit of replaced fresh frozen plasma (p=0.001) was higher in TP group. For its content of coagulant factors, fresh frozen plasma is often preferred to provide hemostasis in our daily practice. However the blood product transfusion is an independent risk factor of high mortality (2). The reexploration on time to prevent massive blood transfusion is important. The surgical hemostasis is vital as well as the hemostatic procedures administered in ICU so are (2).
Among our peroperative findings, the aortic cross-clamping time was longer in TP group (p=0.034) which also involves patients who were operated for more complicated surgeries such as aortic surgery. In recent data, combined cardiac surgeries were associated with higher requirement of platelet transfusion postoperatively (19). Further studies investigating strategies to reduce postoperative TP including reducing CPB time are recommended (8). Additionally cross-clamping time is significantly related with TP in our study.
Cardiovascular dysfunction is better related to outcome with the SOFA score than with the MODS (20). Using the cardiovascular components, outcome prediction was better for the SOFA score at all time intervals in our study. SOFA is applicable to cardiac surgery patients without any modification requirement (9). Accordingly we performed SOFA scoring system for postoperative risk assesment in our study. SOFA scores were not significant between the groups at 12th hour whereas the scores were significantly higher in TP group at 24th and 48th hours (respectively p=0.137; p=0.001; p=0.001). Herein, platelet count, which is also a parameter of SOFA score, was also accomplished alone to predict poor outcome following cardiac surgery.
Although TP was not confirmed to be related significantly with mortality in our study, a higher number of patients who died in hospital were involved in TP group. A total of 30% decline in platelet count is related to mortality in many studies even if it is not under 150,000/μL (21-24).
Concomitant surgical procedures, red blood cell transfusion of >3 units were reported to be associated with prolonged hospital length of stay (25). TP is associated with prolonged lenght of stay both in hospital and intensive care unit following cardiac surgery (respectively p=0.030; p=0.006).
Hemorrhage and prolonged cross clamping time are the significant risk factors associated with TP in our study. Appropriate hemostatic approach begins preoperatively and lasts during intraoperative and postoperative processes (26,27). Principally it should be noted here that an optimal intraoperative surgical hemostasis even during exploration is substantial. To our opinion, an adequate side branch and leakage control, minimizing the tissue damage during the whole operation and spending enough time for bleeding control are considered to be the basic principles.
Optimal temperature, acidity level and appropriate heparin monitoring are some other hemostatic approaches which are called as coagulation-friendly enviroment, although these were not significant variables in our study as were managed in optimal levels in our surgical routine (26).
Minimally invasive extracorporeal circulation, autologous priming, ultrafiltration, cell salvage are some of the technical modifications and supportive methods for blood management (26).
As it is aferomentioned, longer CPB time decrease postoperative platelet count and function (27). Particularly, longer cross clamping time is associated with TP in our study. It was demonstrated that higher cross clamping leads to higher cardioplegia which may result in hemodilution and also platelet dysfunction (26). There are many options to avoid excessive cross-clamping time. On-pump beating heart and off-pump procedures may be beneficial to avoid unfavorable effects of cross-clamping on blood contents (26). Performing proximal anastomosis under side clamping, as double aortic clamping, may be considered as another procedural technique for reducing cross-clamping time (28).
Study Limitations
It was demonstrated that there are safe time limits of aortic cross clamping and CPB time in adult cardiac surgery (28). Consequently a complete or an incomplete revascularization for non-main branches in coronary bypass grafting, is a recent debate. Clinical features would rather influence the choice of a complete or an incomplete revascularization strategy in selected patient categories (29). Although it seems assertive, an incomplete revascularization that skips the non-main branches may be an option particularly when it has to be performed concomitantly with other complicated cardiac procedures and in selected patients to avoid excessive cross clampig time.
Conclusion
In conclusion, early TP may be associated with multiple organ dysfunction and infection; and may be regarded as a remarkable finding of poor prognosis and prolonged length of stay after cardiac surgery. We consider that daily platelet count evaluation in early period following cardiac surgery is an easy and applicable method for assessment of prognosis. Therefore an appropriate hemostatic approach and cross clamping time may be considered as preventive strategies to reduce TP and avoid its causations and consequences, following cardiac surgery.
Acknowledgement
The authors would like to thank F. Nesrin TURAN for her assistance in statistical analysis.
Ethics
Ethics Committee Approval: The study was approved by the local Ethics Commitee (TUTF-GOKAEK 2013/21).
Informed Consent: Informed consent was obtained from all individual participants included in the study.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: G.S.A., O.G., S.H., V.Y., S.C., T.E., Concept: G.S.A., T.E., Design: G.S.A., T.E., Data Collection and Processing: G.S.A., O.G., S.H., V.Y., S.C., T.E., Analysis or Interpretation: G.S.A., T.E., Literature Search: G.S.A., O.G., T.E., Writing: G.S.A., O.G., S.H., V.Y., S.C., T.E.
Conflict of Interest: The authors declared that there was no conflict of interest during the preparation and publication of this article.
Financial Disclosure: This research received no specific grant from any funding agency or the public, commercial, or not-for-profit sectors.
