Clinical Relevance and Practical Value of Platelet Function Assessment Using Multiple Electrode Aggregometry during Extracorporeal Circulation

We read with great interest the recently published study by Mutlak et al.[1] The authors conducted prospective observational study with aim to assess capability of the multiple electrode aggregometry (MEA) to reflect the extent of cardiopulmonary bypass (CPB)–associated platelet dysfunction.[1] Put briefly, platelet function, as assessed by MEA actual deferral percentage (ADP) test, reflected the time-dependent extent of CPB-induced platelet dysfunction.[1] Apart from the fact that study reports the phenomenon that has already been described, some methodological considerations should inevitably be addressed.

Such studies should be focused toward the gaps in our knowledge pertaining to this specific issue.

First of all, the relationship between platelet dysfunction and bleeding outcomes/transfusion requirements should be always validated regardless of cohort size as the effect of sample size on correlation coefficients may easily be calculated. Our working group has recently evaluated predictability of bleeding complications using MEA in pre- and postoperative phase.[2] Even though we reported positive results with bleeding cutoff values being defined using receiver operating curve (ROC) analysis, the fact is that controversial data exist in literature,[2] [3] which in turn necessitates further research to elucidate this field.

Because the platelet dysfunction roots from preoperative antiplatelet drugs or CPB effect, clear distinction between these two plausible causes of platelet dysfunction should be made, as holds great practical value. In our opinion, the influence of preexisting antiplatelet therapy on platelet function should be weighed against the influence of CPB on platelet function. Also, it should be elucidated whether the underlying platelet dysfunction caused by preoperatively administered antiplatelet drugs influences dynamics of platelet function changes during CPB?

In their study,[1] authors considered patients as eligible if not exposed to antiplatelet drugs preoperatively and if their ex vivo arachidonic acid and ADP-induced platelet aggregation were within reference values after the induction of anesthesia.[1] We understand that authors wanted to exclude the possible underlying effects of preoperatively administered antiplatelet drugs to elucidate more precisely the role of CPB itself on platelet function. However, in the real life, a growing number of patients are scheduled for complex procedures with antiplatelet drugs being administered in close proximity to surgery. We need answers on how to manage these patients at particular risk for excessive bleeding. Authors should consider possibility to conduct a new “historically controlled” study in which the findings obtained on patients exposed preoperatively to antiplatelet drugs would be compared with findings obtained in the present study.[1]

Despite emerging evidence on (a) widespread variability in platelet inhibitory response to antiplatelet therapy and (b) the effects of CPB and hypothermia on platelet function, the fact is that use of numerous platelet function testing devices in heterogeneously designed studies hampers pooling of the evidence, which in turn results in the lack of consensus on platelet reactivity level that would be associated with bleeding events in different time points pertaining to the cardiac surgery procedures.

The study by Mutlak et al[1] certainly adds to the current knowledge; however, further research on this field is warranted to provide further refinements in hemostatic management of cardiac surgery patients. There are several knowledge gaps areas that should be addressed in upcoming studies. Next generation of hemostatic algorithms should encompass pre-, intra-, and postoperative time points.

Preoperative part should pertain to risk stratification and measures to prevent bleeding complications. Current guidelines on preoperative antiplatelet administration/discontinuation management rely on “one-size-fits-all” strategy despite emerging evidence on huge individual variability in platelet inhibitory response to antiplatelet drugs. The impact of preoperative antiplatelet drugs on bleeding complications as well as individual variability in platelet inhibitory response should not be underestimated.[2] [4] [5] Using drug-specific platelet function tests preoperatively, the exact cutoff values that increase odds for bleeding complications should be defined and antiplatelet drug administration/discontinuation management should be adjusted accordingly.

Considering intraoperative part of hemostatic management, valuable algorithm has been provided by Weber et al.[6] Authors have shown that hemostatic therapy based on point-of-care testing may reduce patient exposure to allogeneic blood products and provide significant benefits with respect to clinical outcomes.[6] From our standpoint, intraoperative part should remain very similar to that one published by Weber et al,[6] albeit some refinements are required, particularly in defining triggers for transfusion administration.

Cutoff values that delineate bleeding tendency and that are defined throughout prospective studies should be used in transfusion management rather than “normal range” values. Predefined “normal range” values are usually derived from healthy volunteers. If defined throughout prospective studies using ROC analysis, cutoff values may direct transfusion practice most reliably.

Finally, we congratulate authors on timely and elegant study. Moreover, we call for prospective multicentric study that would address all aforementioned methodological considerations and would be conducted in collaboration of centers with expertise in this particular field.

• References

• 1 Mutlak H, Reyher C, Meybohm P , et al. Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation. Thorac Cardiovasc Surg 2015; 63 (1) 21-27
• 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 (1) 2-20
• 3 Schimmer C, Hamouda K, Sommer SP, Özkur M, Hain J, Leyh R. The predictive value of multiple electrode platelet aggregometry (multiplate) in adult cardiac surgery. Thorac Cardiovasc Surg 2013; 61 (8) 733-743
• 4 Drews S, Bolliger D, Kaiser C , et al. Prasugrel increases the need for platelet transfusions and surgical reexploration rates compared with clopidogrel in coronary artery bypass surgery. Thorac Cardiovasc Surg 2015; 63 (1) 28-35
• 5 Al-Lawati AA, Muthuswamy V. Continuing aspirin causes higher drainage even under full protection with antifibrinolytics. Thorac Cardiovasc Surg 2013; 61 (8) 726-730
• 6 Weber CF, Görlinger K, Meininger D , et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology 2012; 117 (3) 531-547