Point-of-Care Platelet Function Testing in Cardiac Surgery: A Bundle of Measures Create Adequate Hemostatic Algorithm.

We read with great interest the recently published study by Agarwal et al.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar The authors of that study conducted a prospective, randomized control trial to investigate whether or not the use of preoperative platelet function testing as a part of transfusion algorithm may reduce transfusion requirements in patients undergoing cardiac surgery.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar Two point-of-care analyzers were evaluated: Multiplate (MEA, Roche Diagnostics, Munich, Germany) and TEG Platelet Mapping (PM, Haemonetics, Braintree, MA).1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar Put briefly, the use of point-of-care devices resulted in reduced frequency and amount of red cells concentrate (RCC), as well as fresh frozen plasma (FFP), at the cost of higher platelet concentrate (PC) transfusion requirements.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar This study1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar certainly added to the current knowledge. However, some methodologic considerations should be addressed. Patient selection was one of the study’s shortcomings.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar This type of study should have narrow focus on one particular subgroup of cardiac surgery patients. The study cohort consisted of elective and urgent coronary artery bypass patients and patients undergoing combined valve plus coronary artery bypass procedures.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar Furthermore, patients undergoing both on- and off-pump coronary artery surgery were included.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar Heterogeneity of the study cohort made it difficult to exclude the effects of cardiopulmonary bypass use as well as the complexity of cardiac surgery procedures on observed primary and secondary outcomes. This heterogeneity of study cohort may have generated confounding factors. Surgery complexity as well as cross-clamp time may have been important confounding factors, particularly in patients not exposed to ADP-receptor blockers preoperatively. In order to eliminate confounding factors, patients should be stratified according to procedure types being performed. Results of this study1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar, as well as literature evidence, support the hypothesis that point-of-care-based hemostatic algorithms may be more useful in patients considered to be at higher risk of bleeding (ie, recent ADP-receptor blockers use). The authors’ effort in designing a transfusion algorithm is laudable. However, further refinements are needed in order to make it more effective and reliable. Despite the transfusion algorithm, the proportion of transfused patients remained high in both the interventional and control arms.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar When analyzing subgroups, a higher percentage of control group patients received red blood concentrate (RCC) and fresh frozen plasma (FFP); while patients with point-of-care platelet function analyzers integrated into the transfusion algorithm more frequently received platelet concentrate (PC), with a higher median number of units transfused.1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar At the same time, the control group had only a 100 mL-higher postoperative chest tube drainage amount. It is, therefore, obvious that there is a lot of room for improvements and that further refinements in the study as well as algorithm designs are necessary to obtain more reliable results. Considering the transfusion algorithm as well as the percentage of transfused patients, we assume that some changes in transfusion triggers should be done to prevent excessive transfusions. In addition, the point-of-care transfusion algorithm shown in this manuscript1Agarwal S, Johnson RI, Shaw M: Preoperative point-of-care platelet function testing in cardiac surgery. J Cardiothorac Vasc Anesth 2014 June 25 [Epub ahead of print]Google Scholar contained competing parameters. What would the authors do if they would have TEG maximum amplitude (TEG-MA) of more than 40 mm coupled with TEG-PM ADP inhibition of more than 70% or MEA less than 30 AUC? Which parameter should be given the priority in deciding to transfuse PC? Preoperative platelet function testing may be useful in terms of preoperative bleeding risk stratification that would direct preoperative antiplatelet drug management as well as timing of surgery. For example, a patient on thienopyridine therapy with high residual on-treatment ADP platelet reactivity may proceed to surgery without drug cessation. Vice versa, pronounced platelet inhibition may advise, cessation of the drug earlier than recommended, with active preoperative measures to restore platelet function and delay of surgery until platelet recovery if the clinical condition allows. Finally, our working group would underline some important considerations for hemostatic management in cardiac surgery patients. (1) Hemostatic algorithms covering the pre-, intra- and postoperative period should be developed and merged into 1 comprehensive algorithm. That algorithm should consist not only of transfusion guidance but also should guide other non-transfusion measures to prevent excessive bleeding and transfusion requirements such as bleeding risk stratification, preoperative antiplatelet drug administration/discontinuation management, and individualized timing of surgery based on the level of platelet function and associated bleeding risk. Furthermore, hemostatic algorithms should be adjusted to the patient subgroups defined in regard to the type of surgery performed. For example, PC transfusions should be avoided in routine cardiac surgery procedures involving coronary revascularization and fibrinogen concentrate targeting optimization of fibrinogen function may substitute for platelet concentrate in this subgroup of patients.2Ranucci M. Fibrinogen supplementation in cardiac surgery: Where are we now and where are we going?.J Cardiothorac Vasc Anesth. 2013; 27: 1-4Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar (2) Intraoperative transfusion management should be based on transfusion triggers defined through prospective studies evaluating the association between point-of-care hemostatic test values and bleeding outcomes/transfusion requirements at the same time. Prospective, non-interventional, clinician-blinded study is the most suitable setting to investigate the relationship among platelet function and postoperative bleeding amount and transfusion requirements, respectively.3Petricevic M. Biocina B. Milicic D. et al.Bleeding risk assessment using whole blood impedance aggregometry and rotational thromboelastometry in patients following cardiac surgery.J Thromb Thrombolysis. 2013; 36: 514-526Crossref PubMed Scopus (43) Google Scholar, 4Petricevic M. Biocina B. Milicic D. et al.Bleeding risk assessment using multiple electrode aggregometry in patients following coronary artery bypass surgery.J Thromb Thrombolysis. 2013; 35: 31-40Crossref PubMed Scopus (45) Google Scholar, 5Petricevic M. Kopjar T. Biocina B. et al.The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: A systematic review.Thorac Cardiovasc Surg. 2014; 63: 2-20Crossref PubMed Scopus (25) Google Scholar Guiding perioperative hemostatic management based only on preoperative testing is of limited value. Transfusion triggers for each time point of surgery should be derived from prospective studies designed to evaluate correlations between point-of-care hemostatic testing performed at the same time and bleeding outcomes/transfusion requirements.5Petricevic M. Kopjar T. Biocina B. et al.The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: A systematic review.Thorac Cardiovasc Surg. 2014; 63: 2-20Crossref PubMed Scopus (25) Google Scholar Of note, there is growing, recently published evidence investigating predictability of bleeding outcomes by point-of-care hemostatic testing performed at different times.3Petricevic M. Biocina B. Milicic D. et al.Bleeding risk assessment using whole blood impedance aggregometry and rotational thromboelastometry in patients following cardiac surgery.J Thromb Thrombolysis. 2013; 36: 514-526Crossref PubMed Scopus (43) Google Scholar, 4Petricevic M. Biocina B. Milicic D. et al.Bleeding risk assessment using multiple electrode aggregometry in patients following coronary artery bypass surgery.J Thromb Thrombolysis. 2013; 35: 31-40Crossref PubMed Scopus (45) Google Scholar, 5Petricevic M. Kopjar T. Biocina B. et al.The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: A systematic review.Thorac Cardiovasc Surg. 2014; 63: 2-20Crossref PubMed Scopus (25) Google Scholar However, pooling of the evidence remains hampered due to non-standardized classification of bleeding and transfusion outcomes. Use of only preoperative point-of-care hemostatic testing for perioperative transfusion management algorithm certainly overlook the impact of cardiopulmonary bypass as well as of surgery itself on platelet function. (3) Selection of the appropriate point-of-care hemostatic device is very important. We suggest that platelet function tests (either shear-stress dependent or impedance aggregometers) should be coupled with either thromboelastometry or thromboelastography. In this way, it is possible to create the most comprehensive picture of overall hemostasis. While platelet function testing should have the major role in the preoperative setting in terms of bleeding risk stratification, modifying antiplatelet drug administration/discontinuation management, and timing of surgery according to platelet recovery, thromboelastometry/thromboelastography should have a major role in defining transfusion triggers during the surgery and in the early postoperative phase. Due to a significant number of patients exposed to dual-antiplatelet therapy preoperatively, the role of aspirin should not be underestimated as it is well known that aspirin and ADP-receptor blockers provide more pronounced platelet inhibition if administered concomitantly than either agent alone. In addition, our working group recently showed that an ASPI test may be useful in predicting early postoperative bleeding.3Petricevic M. Biocina B. Milicic D. et al.Bleeding risk assessment using whole blood impedance aggregometry and rotational thromboelastometry in patients following cardiac surgery.J Thromb Thrombolysis. 2013; 36: 514-526Crossref PubMed Scopus (43) Google Scholar, 4Petricevic M. Biocina B. Milicic D. et al.Bleeding risk assessment using multiple electrode aggregometry in patients following coronary artery bypass surgery.J Thromb Thrombolysis. 2013; 35: 31-40Crossref PubMed Scopus (45) Google Scholar The bleeding amount and transfusion requirements are expected to be inversely related. Therefore, it seems reasonable to create a composite outcome consisting of both the bleeding amount and transfusion requirements as proposed by Rosengart et al6Rosengart T.K. Romeiser J.L. White L.J. et al.Platelet activity measured by a rapid turnaround assay identifies coronary artery bypass grafting patients at increased risk for bleeding and transfusion complications after clopidogrel administration.J Thorac Cardiovasc Surg. 2013; 146: 1259-1266Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar or, more recently, by Dyke et al.7Dyke C. Aronson S. Dietrich W. et al.Universal definition of perioperative bleeding in adult cardiac surgery.J Thorac Cardiovasc Surg. 2014; 147: 1458-1463Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar Standardization of outcomes is very important for further pooling of the evidence, and Dyke et al7Dyke C. Aronson S. Dietrich W. et al.Universal definition of perioperative bleeding in adult cardiac surgery.J Thorac Cardiovasc Surg. 2014; 147: 1458-1463Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar provided the most comprehensive and reliable grading of bleeding outcomes that should be used consistently and validated through further research. We congratulate the authors on their elegant and timely research. This manuscript certainly adds to the current knowledge. However, further efforts to define comprehensive hemostatic algorithms are needed. Standardization in conducting research and defining outcomes is necessary to facilitate pooling of the evidence. Studies should be sufficiently powered to estimate the impact of hemostatic algorithms on clinical outcomes such as mortality and other important albeit rare complications. Thus, multicentric studies certainly are warranted and could be conducted by the collaboration of centers using this technology.