Sanja Konosic

Assessment of platelet function by whole blood impedance aggregometry in coronary artery bypass grafting patients on acetylsalicylic acid treatment may prompt a switch to dual antiplatelet therapy

Residual platelet reactivity (RPR) following coronary artery bypass grafting (CABG) might be related to thrombotic complications and major ischemic cardiac events. The aim of this study was to evaluate the changes in platelet reactivity monitored pre- and postoperatively using multiple-electrode aggregometry (MEA) and to propose an alternative therapeutic approach in a subgroup of patients with postoperative RPR. Ninety-nine patients undergoing elective CABG were enrolled in the study, of whom 41 (41.4%) were diabetic. Preoperatively, all patients received 100 mg acetylsalicylic acid (ASA), with 47 of 99 (47.4%) patients receiving an additional 75 mg clopidogrel (CLO). The blood samples were drawn the day before surgery, and on the first and 4th postoperative day. Platelet count and fibrinogen level were documented, as well as type and daily dose of antiplatelet therapy (APT) received pre- and postoperatively. Multiple-electrode aggregometry using tests based on arachidonic acid (ASPI test) and adenosine diphosphate (ADP test) was performed on the day before and 4 days after surgery. Preoperatively, we detected 31 of 99 (31.3%) patients with RPR (ASPI > 30 AUC). Platelet count correlated with both the ASPI (P = 0.03) and ADP (0.002) tests. Fibrinogen correlated with ADP test values (P < 0.001) and was found to have a higher level in the diabetic subgroup (P = 0.01). In comparison with preoperative results, we detected higher values of ASPI test postoperatively (P = 0.04), with 46 of 99 (46.5%) patients having RPR despite a higher dose of 300 mg ASA being administered. Postoperatively, diabetic patients had higher ASPI test values (P = 0.01), and a higher proportion of patients with RPR compared with the nondiabetic subgroup (58.5 vs 38%, P = 0.04). The subgroup of patients with detected ASPI >30 AUC at the 4th postoperative day consequently received as a part of our clinical routine an additional 75 mg CLO per day, in terms of platelet inhibition optimization. Multiple-electrode aggregometry can recognize patients with RPR during both the pre- and post-CABG period. Postoperatively administered ASA (300 mg) did not sufficiently inhibit platelet aggregation in 46.5% of post-CABG patients. In this group of patients a switch to dual APT should be considered.

Results of extracorporeal life support implementation in routine clinical practice: single center experience

Aim To describe our experience in the clinical application of extracorporeal life support (ECLS) and analyze whether ECLS leads to acceptable clinical outcomes in patients with cardiac failure. Methods Data from clinical database of University Hospital Center Zagreb, Croatia, on 75 patients undergoing ECLS support from 2009 to 2014 due to cardiac failure were retrospectively analyzed. Outcomes were defined as procedural and clinical outcomes. ECLS as a primary procedure and ECLS as a postcardiotomy procedure due to inability to wean from cardiopulmonary bypass were analyzed. Results ECLS was used in 75 adult patients, and in 24 (32%) of those procedural success was noted. ECLS was implemented as a primary procedure in 36 patients and as a postcardiotomy procedure in 39 patients. Nine out of 39 (23.08%) patients had postcardiotomy ECLS after heart transplantation. Bleeding complications occurred in 30 (40%) patients, both in primary (11/36 patients) and postcardiotomy group (19/39 patients). ECLS was established by peripheral approach in 46 patients and by central cannulation in 27 patients. In 2 patients, combined cannulation was performed, with an inflow cannula placed into the right atrium and an outflow cannula placed into the femoral artery. Eleven patients treated with peripheral approach had ischemic complications. Conclusion ECLS is a useful tool in the treatment of patients with refractory cardiac failure and its results are encouraging in patients who otherwise have an unfavorable prognosis.

Impact of aspirin resistance on antiplatelet therapy management after coronary artery surgery

Dual antiplatelet therapy (APT) provides incremental platelet inhibition compared with either agent alone and more effective suppression of adverse ischaemic events [2]. This finding is confirmed by Awidi and coworkers who found that the combination of aspirin and clopidogrel had greater inhibitory effects on platelet aggregation than either agent alone in patients with coronary artery disease [3]. In our opinion, the addition of clopidogrel in the group of patients with AR inevitably affected both the observed clinical outcomes and the decrease in AR proportion. Following CAS, extensive evidence supports the use of aspirin, in doses of 100–325 mg/day, to be administered postoperatively and continued indefinitely [4]. A daily 100 mg dose of aspirin administered postoperatively in a study by Wang et al. [1], allows the possibility of different APT management strategies. For example, a stepwise increase in the aspirin dose with a subsequent platelet function assessment could probably bring a further decrease in the AR proportion and therefore, eliminate the need for dual APT. However, it still remains unclear, whether an aspirin dose increase would be superior to dual APT, in the context of a clinical outcome. Of note, a meta-analysis by Snoep et al. showed an overall prevalence of 21% of laboratory-defined clopidogrel low response [5]. We believe that these two different APT approaches should be evaluated in a large cohort randomized trial with an outcome evaluation of both ischaemic and bleeding events. The authors hypothesized that the Chinese population is more sensitive to aspirin therapy and presented no AR at a 6-month follow-up. It would be interesting if the authors analyzed the bleeding event occurrence at the 6-month follow-up in the group of patients on dual APT. APT management in cases of AR should be individually tailored, with aspirin dosage stepwise increased (up to 325 mg/day), and clopidogrel administration in cases of AR to high aspirin doses. Temporary AR requires temporary APT adjustment. The duration and intensity of the APT adjustment should be tailored according to drug specific platelet function tests in order to minimize both ischaemic and bleeding events. In conclusion, it is difficult to investigate by what amount the laboratory AR corresponds to the clinical AR. Prospective studies, with a large study sample necessitated by the infrequency of adverse ischaemic events, must determine the optimal threshold for AR, taking into consideration both the laboratory and clinical outcome findings.

Definition of aspirin resistance using whole blood impedance aggregometry in patients undergoing coronary artery surgery: methodological challenges and outcome improvement opportunities

Methods Prospective observational trial at University Hospital Center Zagreb enrolled 131 patients scheduled for CABG, and divided them into 4 groups with respect to preoperative antiplatelet therapy (APT). Group 1 received 100 mg ASA per day, Group 2 100 mg ASA + 75 mg clopidogrel per day, Group 3 75 mg clopidogrel per day, and Group 4 did not receive any APT. MEA with ASPI test (sensitive to ASA) and ADP test (sensitive to clopidogrel) was performed prior to surgery. In Group 1, patients were characterized as ASA resistant if their ASPI test value exceeded the 75th percentile distribution. Results Study enrolled 131 patients. Significant differences both in the ASPI (p<0.001) and the ADP test (p=0.038) were observed between patients in different APT groups. In Group (1) ASPI test value of 30 AUC presented 75th percentile of distribution, thus indicating ASA resistance. Group 2 patients had slightly lower ADP test values, but no significant difference occurred (mean 60.05 vs. 63.32 AUC, p=0.469). In Group 1 and 2, significant correlations between the ADP test and both, platelet count (r=0.347, p<0.001) and fibrinogen level (r=0.364, p<0.001) were observed.

Preoperative aspirin use and outcomes in cardiac surgery patients: a role of platelet function assessment.

To the Editor: W e read with great interest the recently published study by Cao et al.1 Patients were divided into 2 groups: those taking (n = 1923) or not taking (n = 945) aspirin within 5 days preceding surgery.1 The authors compared 2 groups according to outcomes such as 30-day all-cause mortality, postoperative renal failure/dialysis required, and a composite outcome—major adverse cardiocerebral events (MACE); the latter included permanent or transient stroke, coma, perioperative myocardial infarction, heart block, and cardiac arrest.1 Other outcomes were readmission and intensive care unit stay. The authors showed that preoperative aspirin therapy (vs nonaspirin) significantly reduced the risk of 30-day mortality (P = 0.031), postoperative renal failure (P < 0.001), dialysis required (P < 0.001), intensive care unit stay (P < 0.001), and a composite MACE outcome (P = 0.011).1 In our opinion, the lack of objective quantification of the antiplatelet effect of aspirin in the group of patients taking aspirin within 5 days preceding surgery constitutes a major drawback of the study. Expected inhibition of platelet function is not always achieved after aspirin administration. Literature reports already described a wide variability in platelet response to aspirin therapy, with prevalence of aspirin resistance, as defined by platelet function tests, ranging from 1% to 45%.2 Residual platelet reactivity, the so-called, aspirin resistance, after aspirin administration might be related to thrombotic complications and major ischemic events, both preand postoperatively despite aspirin administration.3 As Cao et al1 described, most patients underwent coronary arteries revascularization (n = 1916; 66.8%), either in the form of isolated coronary artery bypass grafting (CABG) (n = 1474; 51.4%) or valve plus CABG (n = 442; 15.4%).1 Aortocoronary vein graft disease comprises 3 distinct but interrelated pathological processes: thrombosis, intimal hyperplasia, and atherosclerosis. Early thrombosis is a major cause of vein graft attrition during the first month after surgical procedure4 and inevitably influences the composite MACE outcome in the study by

How to prevent bleeding events in on- and off-pump coronary artery bypass patients exposed to clopidogrel preoperatively

The effect of clopidogrel on bleeding mainly depends on two factors: (1) observed platelet inhibition, which is depending on inherent platelet activity prior to clopidogrel administration and platelet inhibitory response to clopidogrel and (2) newborn platelets ability to restore normal aggregation after clopidogrel discontinuation.The role of aspirin and clopidogrel on bleeding should separately be assessed by drug specific platelet function tests, facilitating individual therapeutic approach for each antiplatelet agent preoperatively. Such an approach could distinguish patients with high residual platelet activity, thus proclivity to ischemic events, or enhanced platelet inhibition, thus proclivity to excessive bleeding. It would be interesting if authors compared preoperative ischemic events incidence between patients groups with respect to preoperative clopidogrel treatment. Timing of discontinuation as well as intensity of preoperatively administered aspirin and clopidogrel should be tailored according to drug specific platelet function tests in order to minimize both ischemic and bleeding events. In group of patients with pronounced platelet inhibition after aspirin and/or clopidogrel administration, early antiplatelet drug discontinuation should be considered. For elective patients, delaying of surgery in cases of pronounced platelet inhibition after antiplatelet drugs administration should be considered if clinically condition allows. For urgent and/or emergent cases with observed preoperative deep platelet inhibition, the desmopressin administration should be considered [5] as well as intraoperative thromboelastography guided hemostatic therapy which significantly reduces incidence of overall transfusion and mediastinal re-exploration due to excessive bleeding [6]. However, such an approach requires further studies in order to provide platelet function test cut-off values that delineate bleeding as well as ischemic events. According to obtained cut-off values, antiplatelet therapy management should be evaluated in context of clinical outcome.

Haemostatic management in high-risk cardiac surgery : a role of recombinant factor VIIa (NovoSeven RT)

We read with great interest the recently published retrospective study by Chapman et al .[ 1]. The authors matched 236 patients with recombinant factor VIIa (rFVIIa) administration with a control group of 213 patients without rFVIIa treatment. The majority of procedures involved coronary artery bypass graft surgery: 51.7% in the rFVIIa group and 53.5% in the control group. We are interested whether those patients were preoperatively exposed to anti-thrombotic therapy with acetylsalicylic acid and/or clopidogrel. If so, was the proportion of patients with either mono or dual preoperative anti-thrombotic therapy different among the groups? Did the authors perform a platelet function test prior to the procedure in order to determine the platelet function? The acquired platelet function disorder plays a major role in perioperative bleeding in cardiac surgery. Therefore, the use of point-of-care suitable platelet function analysers seems to be reasonable in this field. The rFVIIa group had a significantly higher rate of re-operation for bleeding, a two fold increase in the use of blood products and, more frequently, had pulmonary complications. In addition, Hacquard et al .[ 2] have reported 20% of patients with rFVIIa administration who continued to bleed severely despite rFVIIa therapy. The rFVIIa group received rFVIIa after bleeding had not responded to traditional therapy, and some of the patients received one or two additional doses. It remains unclear whether the traditional blood component administration was targeted after intraoperative thromboelastography haemostatic property assessment. Spiess et al. have reported thromboelastography-guided haemostatic management to significantly reduce the incidence of the overall transfusion and mediastinal re-exploration due to excessive bleeding [3]. Targeted therapy enables more efficient haemostatic treatment, based on functional deficiency, thus leading to lower dosages of blood component therapy. Furthermore, thromboelastography-guided haemostatic therapy with the reduced and targeted procoagulant blood component administration can reduce respiratory complications. Optimization of haemostatic properties, guided by thromboelastography, can lead to diminished use of rFVIIa and, if rFVIIa is deemed necessary, its efficiency could be better after functional haemostatic property optimization. We believe that intraoperative haemostatic property optimization guided by viscoelastic tests of whole-blood coagulation and platelet function should precede rFVIIa administration. Such an approach can improve the rFVIIa efficiency and therefore diminish the 11% prevalence of patients requiring re-exploration despite rFVIIa administration. In our experience, algorithms for perioperative coagulation management based on the point-of-care testing permit a fast diagnostic and goaldirected therapy of coagulation and functional platelet disorders with only sporadic need for rFVIIa administration. We congratulate the authors on their elegant and timely research.

Effects of corticosteroids after total reapair of congenital heart desease with extracorporeal circulation

Background Nowadays, the use of cardiopulmonary bypass (CPB) followed by systemic hypothermia is common in cardiac surgery procedures. CPB causes a systemic inflammatory response syndrome (SIRS) that is markedly expressed in congenital caridiosurgical surgery programe resulting with deleterious consequences. Those effects are mediated through cytokines and others mediators of acute inflammatory response in circulation, which may lead to low cardiac output syndrome, multiorgan failure and lethal outcome after surgical total correction of congenital heart disease. The best method for SIRS prevention remains unclear, although some authors suggest perioperative use of corticosteroids. The study sough to evaluate the impact of perioperative corticosteroids on SIRS extent as well as clinical outcomes following total correction of congenital heart disease.

Benefits and risks of using clopidogrel before coronary artery bypass surgery: A role of platelet function assessment

Reply to the Editor: We thank Drs Nosotti, Simone, and Cioffi for their kind remarks and excellent commentary regarding our recent publication. Endobronchial ultrasoundguided transbronchial needle aspiration (EBUS-TBNA) is truly an emerging technology that allows safe and accurate assessment of the mediastinum in patients with non–small cell lung cancer. We also anticipate the results of the ASTER trial with hopes that it will further validate our findings. We also understand the valid point made regarding the utility of rapid onsite evaluation during EBUS-TBNA. To this end, recent studies have sought to investigate the utility of rapid on-site evaluation. However, in a practical sense, it may not always be possible to have access to the service of an experienced cytopathologist at all times during the performance of EBUS-TBNA. Practice patterns ultimately are developed with the resources that are available within a given institution. Altogether, EBUS-TBNA provides a safe and reliable method of assessing the mediastinum in patients with non– small cell lung cancer. Whether the results are available instantaneously or in a couple of days, what matters the most is achieving an accurate result.

How To Manage Aspirin Resistance Early After Coronary Artery Bypass Grafting

1. Slinger P: Con: The new bronchial blockers are not preferable to ouble-lumen tubes for lung isolation. J Cardiothorac Vasc Anesth 2:925-929, 2008 2. Brodsky JB: Lung separation and the difficult airway. Br J Anesth 103:i66-i75, 2009 (suppl 1) 3. Fitzmaurice BG, Brodsky JB: Airway rupture from double-lumen ubes. J Cardiothorac Vasc Anesth 13:322-329, 1999 4. Campos JH: Which device should be considered the best for lung solation: Double-lumen endotracheal tube versus bronchial blockers. urr Opin Anaesthesiol 20:27-31, 2007 5. Abu Alhaija ES, Al Bhairan HM, Al Khateeb SN: Mandibular hird molar space in different antero-posterior skeletal patterns. Eur Orthod 33:570-576, 2011 6. Truong A, Truong DT: Retromolar fibreoptic orotracheal intubaion in a patient with severe trismus undergoing nasal surgery. Can J naesth 58:460-463, 2011