The Association Between Perioperative Point-of-Care Platelet Function Analyses and Transfusion Requirements in Cardiac Surgery: Methodological Considerations
We read with great interest the recently published study by Wang et al. The authors conducted retrospective study comparing bleeding and transfusion outcomes in patients undergoing coronary artery surgery before and after implementation of Multiplate-guided transfusion algorithm.
Study by Wang et al certainly adds to the current knowledge; however, some methodological considerations should inevitably be addressed. Multiplate results were correlated to bleeding amount/transfusion requirements. This may pose a great confounding factor here as the Multiplate results were used to guide platelets transfusion. This bias inevitably alters the correlations and provides unreliable Multiplate cutoff points. This methodological flaw may to some degree explain why authors reported different cutoff values relative to those existing in the literature. Another reason for differences in cutoff values may be the anticoagulant used for blood sample collection (i.e., hirudin vs. heparin). From the methodological viewpoint, Multiplate results should not be correlated with transfusion requirements if Multiplate was used to guide transfusion management.
When conducting research on the association between platelet function testing and bleeding complications/transfusion requirements, authors should be aware of the entire evidence available so far. It looks like the current evidence pertaining to this research question has not been reviewed systematically. Authors mentioned that most of the available studies are limited by the sample size and retrospective nature of data collection however, few prospective observational studies using Multiplate in noninterventional research setting have not been mentioned. A thorough insight into available evidence is mandatory to better understand the gaps in knowledge and to appropriately set the research question.
When considering the antiplatelet therapy (APT) discontinuation management, we need more precise (i.e., drug specific) information on discontinuation period. Five days of discontinuation period should refer to clopidogrel discontinuation solely (even though there is some evidence suggesting even shorter timeframe to discontinue clopidogrel if coupled with Multiplate ADP test). Widely used ticagrelor should be discontinued 3 days, whereas prasugrel should be discontinued 7 days prior to surgery. Current guidelines suggest Aspirin continuation throughout perioperative period, even though some studies suggest that there may be some proportion of patients with pronounced and prolonged platelet inhibitory response to Aspirin who could possibly benefit from preoperative Aspirin discontinuation.
Perioperative platelet dysfunction roots either from (1) preoperative (APT) or (2) intraoperative (cardiopulmonary bypass [CPB]) effect. Clear distinction between these two plausible causes of platelet dysfunction should be made, as it holds great practical value. In present study, preoperative Multiplate testing directed transfusion that is somewhat unreliable as the effect of the CPB on the platelets function remains unknown. For example, the patient with adequate platelet function before surgery will not be transfused even after long CPB time that certainly decreases platelet function. According to our experience, the strongest and the most reliable correlations between Multiplate results and bleeding outcomes/transfusion requirements were noted for the measurements performed after protamine administration, whereas preoperative testing is primarily used for bleeding risk stratification and guiding timing of surgery in context of APT discontinuation. The effect of ADP receptor blockers depends on (1) baseline, inherent platelet ADP receptor activity, (2) platelet inhibitory response to antiplatelet drug, as well as on (3) recovery rate of platelet function after drug discontinuation. Additionally, recovery of platelet function following drug discontinuation could be quantified by serial platelet function testing and once platelet function outgrows predefined cutoff value that delineates bleeding tendency, it would be safe to proceed with surgery regardless the number of days following drug cessation. This personalized approach may shorten waiting time and optimize bleeding and transfusion outcomes at the same time. Authors may simply calculate positive and negative predictive values for the existing cutoff values and in case of preoperative tests, detect who should not be transfused given the sufficient platelet function.
We need methodological consensus on the study design and definition of bleeding events. Authors reported the use of UDPB (universal definition of perioperative bleeding) in their study but the results are not presented in context of UDPB?!
The study by Wang et al certainly adds to the current knowledge. Preoperative platelet function testing may be very useful, however, more useful in terms of bleeding risk stratification and possible guiding the timing of surgery in context of recent APT exposure, rather than guiding procoagulant blood components transfusion. Further research in this field is warranted to provide further refinements in hemostatic management.
Received: 24 June 2020
Accepted: 13 July 2020
18 February 2021 (online)
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- 1 Wang L, Valencia O, Phillips S, Sharma V. Implementation of perioperative point-of-care platelet function analyses reduces transfusion requirements in cardiac surgery: a retrospective cohort study. Thorac Cardiovasc Surg 2020; DOI: 10.1055/s-0040-1710582.
- 2 Petricevic 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 2015; 63 (01) 2-20
- 3 Petricevic M, Knezevic J, Biocina B. et al. Association among clopidogrel cessation, platelet function, and bleeding in coronary bypass surgery: an observational trial. Thorac Cardiovasc Surg 2019; DOI: 10.1055/s-0039-1693122.