© 2014 Wiley Periodicals, Inc.
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LETTER TO THE EDITOR __________________________________________________________
Bleeding Risk Assessment Using Point-of-Care Platelet Function Testing in Patients Undergoing Coronary Artery Surgery: How to Improve Predictability Mate Petricevic, M.D., Ph.D.,*Bojan Biocina, M.D., Ph.D.,* Marko Boban, M.D., Ph.D.,yJure Samardzic, M.D.,zMartina Zrno Mihaljevic, M.D.,* and Davor Milicic, M.D., Ph.D.z *Department of Cardiac Surgery, School of Medicine, University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia; yDepartment of Cardiology, University Hospital ‘‘Thalassotherapia Opatija’’, Medical School University of Rijeka and Osijek, Opatija, Croatia; and zDepartment of Cardiovascular Diseases, School of Medicine University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia doi: 10.1111/jocs.12371 (J Card Surg 2014;29:806–807) We read with great interest the recently published paper by Yu et al.1 The authors conducted prospective study with aim to evaluate prediction of bleeding amount and transfusion requirements using platelet function testing in patients undergoing coronary artery surgery (CAS).1 Put briefly, platelet function testing failed to predict platelets transfusion and chest tube amount in patients preoperatively exposed to P2Y12 inhibitors.1 We have some comments that, we believe, should be addressed in such a type of study. The study was conducted in prospective observational fashion.1 However, we miss clear study protocol for platelet function testing. Nine patients with baseline P2Y12 reaction unit (PRU) values of less than 250 were excluded, as tests were not repeated within 24 hours of surgery.1 Since PRU results were not blinded, it remains unclear whether PRU results were part of the clinical decision making process (i.e., guiding transfusion management and timing of the surgery). If so, that could hamper sensitivity of the platelet function test as timing of surgery until platelet
Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Mate Petricevic, M.D., Ph.D., Department of Cardiac Surgery, School of Medicine, University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. Fax: þ38152367531; e-mail: [email protected]
recovery as well as tailored platelet concentrate transfusion in patients with weak platelet function may certainly affect correlations with observed primary end-points. In contrast to findings reported in the present study,1 Rosengart et al.2 showed that the risks of bleeding and transfusion in patients undergoing CAS after P2Y12 inhibitors administration can be successfully predicted using the same point-of-care platelet reactivity assay. A prospective, noninterventional, clinician-blinded study that is sufficiently powered (using sample size calculator) is the most suitable setting to investigate the association between point-of-care platelet function tests and clinical end-points such as postoperative bleeding amount and transfusion requirements. It seems reasonable to merge bleeding amount and platelet concentrate transfusion into a composite end-point, as they are expected to be inversely related.2 International Initiative for Hemostasis Management in Cardiac Surgery recently proposed a universal multistage definition of perioperative bleeding that accounts for all relevant variables influencing bleeding-related complications.3 In a type of study such as the present one by Yu et al.1 the use of this standardized grading of bleeding outcome3 may allow for the most precise and reliable correlations, thus leading to meaningful conclusions. Finally, the role of preoperative aspirin administration should not be underestimated as there is evidence that some patients have accentuated and prolonged response to aspirin that may increase the
J CARD SURG 2014;29:806–807
PETRICEVIC, ET AL. LETTER TO THE EDITOR
risk of perioperative bleeding.4 In addition, there is evidence that dual antiplatelet therapy with aspirin and clopidogrel provides incremental platelet inhibition compared with each agent administered alone.5 Considering the fact that the majority of patients were exposed to aspirin in the present study,1 it would be interesting to see if concomitant use of aspirin-sensitive assay would increase predictability of bleeding outcomes. We congratulate the authors on their elegant and timely research. REFERENCES 1. Yu PJ, Cassiere HA, Dellis SL, et al: P2Y12 platelet function assay for assessment of bleeding risk in coronary artery bypass grafting. J Card Surg. 2014. doi: 10.1111/jocs.12312
AUTHOR’S RESPONSE TO THE LETTER TO THE EDITOR We greatly appreciate the comments of Petricevic and colleagues regarding our article on the use of P2Y12 point-of-care platelet function testing to assess bleeding risk in patients who are undergoing isolated coronary artery bypass grafting (CABG).1 While the study by Rosengart et al.2 showed that preoperative platelet function testing can identify those at increased risk for post-operative bleeding and transfusion, our study using the same point-of-care platelet function assay demonstrated no association between the results of the assay and operative bleeding risk. Although both studies looked at patients undergoing isolated CABG, 40% of patients in the study by Rosengart et al. underwent off-pump surgery as compared to 8.4% in our study. As cardiopulmonary bypass is known to cause platelet dysfunction and the time on cardiopulmonary bypass is correlated to the need for platelet transfusions, the two studies are looking at two very different cohorts of patients, and the results of these two studies may therefore not be comparable. Studies looking specifically at either on-pump or off-pump CABGs are therefore needed to further delineate the impact of cardiopulmonary bypass on the utility of preoperative platelet function testing. In addition, while studies blinding PRU results may be difficult to conduct in light of the blood conservation
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2. Rosengart TK, Romeiser JL, White LJ, 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– 1266 1266 e1251; discussion 1266. 3. Dyke C, Aronson S, Dietrich W, et al: Universal definition of perioperative bleeding in adult cardiac surgery. J Thorac Cardiovasc Surg. 2013. doi: 10.1016/j.jtcvs.2013.10.070 4. Ferraris VA, Ferraris SP, Joseph O, et al: Aspirin and postoperative bleeding after coronary artery bypass grafting. Ann Surg 2002;235:820–827. 5. Awidi A, Saleh A, Dweik M, et al: Measurement of platelet reactivity of patients with cardiovascular disease ontreatment with acetyl salicylic acid: A prospective study. Heart Vessels 2011;26:516–522.
guidelines that recommend its use in preoperative patients,3 we agree with Petricevic et al. that further sufficiently powered studies that utilize a standard grading system for postoperative bleeding are warranted to determine the role of point-of-care platelet function testing in CABG patients receiving preoperative P2Y12 inhibitors. Pey-Jen Yu, M.D. Hugh A. Cassiere, M.D. Department of Cardiovascular and Thoracic Surgery North Shore University Hospital Manhasset, New York e-mail: [email protected] REFERENCES 1. Yu PJ, Cassiere HA, Dellis SL, et al: P2Y12 platelet function assay for assessment of bleeding risk in coronary artery bypass grafting. J Card Surg. 2014. doi: 10.1111/jocs.12312 2. Rosengart TK, Romeiser JL, White LJ, 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– 1266 1266 e1251; discussion 1266. 3. Ferraris VA, Brown JR, Despotis GJ, et al: 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011;91:944– 982.
Copyright of Journal of Cardiac Surgery is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
806
LETTER TO THE EDITOR __________________________________________________________
Bleeding Risk Assessment Using Point-of-Care Platelet Function Testing in Patients Undergoing Coronary Artery Surgery: How to Improve Predictability Mate Petricevic, M.D., Ph.D.,*Bojan Biocina, M.D., Ph.D.,* Marko Boban, M.D., Ph.D.,yJure Samardzic, M.D.,zMartina Zrno Mihaljevic, M.D.,* and Davor Milicic, M.D., Ph.D.z *Department of Cardiac Surgery, School of Medicine, University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia; yDepartment of Cardiology, University Hospital ‘‘Thalassotherapia Opatija’’, Medical School University of Rijeka and Osijek, Opatija, Croatia; and zDepartment of Cardiovascular Diseases, School of Medicine University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia doi: 10.1111/jocs.12371 (J Card Surg 2014;29:806–807) We read with great interest the recently published paper by Yu et al.1 The authors conducted prospective study with aim to evaluate prediction of bleeding amount and transfusion requirements using platelet function testing in patients undergoing coronary artery surgery (CAS).1 Put briefly, platelet function testing failed to predict platelets transfusion and chest tube amount in patients preoperatively exposed to P2Y12 inhibitors.1 We have some comments that, we believe, should be addressed in such a type of study. The study was conducted in prospective observational fashion.1 However, we miss clear study protocol for platelet function testing. Nine patients with baseline P2Y12 reaction unit (PRU) values of less than 250 were excluded, as tests were not repeated within 24 hours of surgery.1 Since PRU results were not blinded, it remains unclear whether PRU results were part of the clinical decision making process (i.e., guiding transfusion management and timing of the surgery). If so, that could hamper sensitivity of the platelet function test as timing of surgery until platelet
Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Mate Petricevic, M.D., Ph.D., Department of Cardiac Surgery, School of Medicine, University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. Fax: þ38152367531; e-mail: [email protected]
recovery as well as tailored platelet concentrate transfusion in patients with weak platelet function may certainly affect correlations with observed primary end-points. In contrast to findings reported in the present study,1 Rosengart et al.2 showed that the risks of bleeding and transfusion in patients undergoing CAS after P2Y12 inhibitors administration can be successfully predicted using the same point-of-care platelet reactivity assay. A prospective, noninterventional, clinician-blinded study that is sufficiently powered (using sample size calculator) is the most suitable setting to investigate the association between point-of-care platelet function tests and clinical end-points such as postoperative bleeding amount and transfusion requirements. It seems reasonable to merge bleeding amount and platelet concentrate transfusion into a composite end-point, as they are expected to be inversely related.2 International Initiative for Hemostasis Management in Cardiac Surgery recently proposed a universal multistage definition of perioperative bleeding that accounts for all relevant variables influencing bleeding-related complications.3 In a type of study such as the present one by Yu et al.1 the use of this standardized grading of bleeding outcome3 may allow for the most precise and reliable correlations, thus leading to meaningful conclusions. Finally, the role of preoperative aspirin administration should not be underestimated as there is evidence that some patients have accentuated and prolonged response to aspirin that may increase the
J CARD SURG 2014;29:806–807
PETRICEVIC, ET AL. LETTER TO THE EDITOR
risk of perioperative bleeding.4 In addition, there is evidence that dual antiplatelet therapy with aspirin and clopidogrel provides incremental platelet inhibition compared with each agent administered alone.5 Considering the fact that the majority of patients were exposed to aspirin in the present study,1 it would be interesting to see if concomitant use of aspirin-sensitive assay would increase predictability of bleeding outcomes. We congratulate the authors on their elegant and timely research. REFERENCES 1. Yu PJ, Cassiere HA, Dellis SL, et al: P2Y12 platelet function assay for assessment of bleeding risk in coronary artery bypass grafting. J Card Surg. 2014. doi: 10.1111/jocs.12312
AUTHOR’S RESPONSE TO THE LETTER TO THE EDITOR We greatly appreciate the comments of Petricevic and colleagues regarding our article on the use of P2Y12 point-of-care platelet function testing to assess bleeding risk in patients who are undergoing isolated coronary artery bypass grafting (CABG).1 While the study by Rosengart et al.2 showed that preoperative platelet function testing can identify those at increased risk for post-operative bleeding and transfusion, our study using the same point-of-care platelet function assay demonstrated no association between the results of the assay and operative bleeding risk. Although both studies looked at patients undergoing isolated CABG, 40% of patients in the study by Rosengart et al. underwent off-pump surgery as compared to 8.4% in our study. As cardiopulmonary bypass is known to cause platelet dysfunction and the time on cardiopulmonary bypass is correlated to the need for platelet transfusions, the two studies are looking at two very different cohorts of patients, and the results of these two studies may therefore not be comparable. Studies looking specifically at either on-pump or off-pump CABGs are therefore needed to further delineate the impact of cardiopulmonary bypass on the utility of preoperative platelet function testing. In addition, while studies blinding PRU results may be difficult to conduct in light of the blood conservation
807
2. Rosengart TK, Romeiser JL, White LJ, 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– 1266 1266 e1251; discussion 1266. 3. Dyke C, Aronson S, Dietrich W, et al: Universal definition of perioperative bleeding in adult cardiac surgery. J Thorac Cardiovasc Surg. 2013. doi: 10.1016/j.jtcvs.2013.10.070 4. Ferraris VA, Ferraris SP, Joseph O, et al: Aspirin and postoperative bleeding after coronary artery bypass grafting. Ann Surg 2002;235:820–827. 5. Awidi A, Saleh A, Dweik M, et al: Measurement of platelet reactivity of patients with cardiovascular disease ontreatment with acetyl salicylic acid: A prospective study. Heart Vessels 2011;26:516–522.
guidelines that recommend its use in preoperative patients,3 we agree with Petricevic et al. that further sufficiently powered studies that utilize a standard grading system for postoperative bleeding are warranted to determine the role of point-of-care platelet function testing in CABG patients receiving preoperative P2Y12 inhibitors. Pey-Jen Yu, M.D. Hugh A. Cassiere, M.D. Department of Cardiovascular and Thoracic Surgery North Shore University Hospital Manhasset, New York e-mail: [email protected] REFERENCES 1. Yu PJ, Cassiere HA, Dellis SL, et al: P2Y12 platelet function assay for assessment of bleeding risk in coronary artery bypass grafting. J Card Surg. 2014. doi: 10.1111/jocs.12312 2. Rosengart TK, Romeiser JL, White LJ, 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– 1266 1266 e1251; discussion 1266. 3. Ferraris VA, Brown JR, Despotis GJ, et al: 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011;91:944– 982.
Copyright of Journal of Cardiac Surgery is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
