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Re: Thrombelastography® Platelet MappingTM is a useful preoperative tool in surgical patients taking antiplatelet medication
- Thomas C Collyer, Doug J Gray (26 May 2009)
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Thrombelastography® Platelet MappingTM is a useful preoperative tool in surgical patients taking antiplatelet medication
- Jasmeet Kaur, Nicola Jones, Susan Mallett (19 May 2009)
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Thomas C Collyer , Doug J Gray
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We thank Jasmeet Kaur and colleagues for their interest in our recent paper and for the opportunity to respond to some of the very interesting points that they raise. Our statement “it is currently unknown as to what level of ex- vivo platelet receptor inhibition signifies normal or abnormal platelet function and how clinical endpoints, such as bleeding, correlate to ex-vivo platelet receptor inhibition” is in fact very similar to the conclusions drawn by the authors themselves in their recent paper: “As yet, there are no data that predict at what level of platelet inhibition bleeding is likely to occur or when it is safe to perform invasive procedures”.1 They go on to conclude that further clinical trials are necessary. Interestingly, they formed these conclusions two years after publication of the paper they refer to in their letter, by Chen et al.2 The work by Chen et al raises a number of interesting points. The bleeding risks associated with patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass are well known; indeed, in this study 53% of patients with prior exposure to clopidogrel and 13% of control subjects received platelet transfusions.2 In our study, however, none of the 59 patients recruited received a platelet transfusion. Chen et al showed that severe preoperative platelet dysfunction identified by Light Transmission Aggregometry (LTA) predicted 11 of 12 cases of severe coagulopathy requiring multiple transfusions. However, all 11 of these cases received platelet transfusions intraoperatively, guided by the Platelet Function Analyser 100 (PFA 100) and not LTA, according to their study protocol. The PFA 100 has not been shown to correlate well with platelet dysfunction secondary to clopidogrel therapy.1 It is possible therefore that some of these transfusions were not indicated. For both these reasons we would advise caution in extrapolating the use of LTA in predicting bleeding in CABG patients, to the acute general surgical population. In the paper by Agarwal et al the authors state, “There is no ideal method of assessing platelet function. LTA is one of the standard methods used in hemostasis laboratories. However, it is poorly standardized across laboratories, particularly in terms of the use of various types and concentrations of agonists to demonstrate drug effect, and therefore, it is difficult to compare the results from different hospitals.”1 This is an important point. Despite using a range of concentration of ADP activator for LTA in their study (2 – 5 µM), when analysing agreement between LTA and modified thrombelastography (mTEG), a concentration of 5 µM was used.1 Chen et al used a concentration of 2 µM again, extrapolating predictive values for bleeding between the two papers, in our opinion, requires caution. Agarwal et al demonstrated good agreement between LTA and mTEG in patients on clopidogrel therapy, κ 0.81, with agreement in 14 of 20 patients. In 10 patients identified as having a definitive response to clopidogrel by LTA, 7 patients were also identified by mTEG. However, conversely, 3 patients (30%) were false negatives. In patients taking both clopidogrel and aspirin, mTEG correctly identified only 5 out of 10 patients, a 50% false negative rate. Therefore if mTEG was used alone a proportion of patients would have been cleared for surgery and anaesthesia despite having definitive ADP receptor platelet inhibition. Perhaps most importantly in our paper, the finding of a wide range of both platelet ADP and TxA2 receptor inhibition in the control group remains unexplained. The issue concerning the concentration of platelet receptor agonists has been discussed. The potential for a high false positive rate is therefore of concern and, as we highlighted, requires further investigation. Finally, we are equally excited about the potential of point of care tests of platelet function. There is huge potential for tailoring the timing of surgery, informing the use of neuroaxial anaesthesia, guiding blood product transfusions and identifying at-risk non-responders to antiplatelet agents. However, as we concluded, more work is required with TEG platelet mapping before truly evidence-based guidance can be offered. References 1 Agarwal S, Coakley M, Reddy K, Riddell M, Mallett S. Quantifying the effect of antiplatelet therapy: a comparison of the Platelet Function Analyser (PFA-100) and Modified Thromboelastography (mTEG) with Light Transmission Platelet Aggregometry. Anesthesiology 2006; 105: 676-83 2 Chen L et al. Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting. J Thorac Cardiovasc Surg 2004; 128: 425-31 Conflict of Interest:None declared |
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Jasmeet Kaur, Anaesthetic SpR Royal Free Hospital London, Nicola Jones, Susan Mallett
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We read with interest the article by T.C. Collyer et al to assess platelet inhibition secondary to aspirin and clopidogrel therapy in preoperative surgical patients. The authors state in their conclusion that it is currently unknown as to what level of ex vivo platelet receptor inhibition correlates to normal or abnormal function and how indeed this correlates to bleeding. Chen et al(1) used Light Transmission Aggregometry(LTA) which is recognised as the gold standard for the measurement of platelet function and is able to detect the effects of antiplatelet therapy, to determine platelet function and used this information to predict coagulopathy and bleeding in patients undergoing cardiac surgery. They used values of 70-100% light transmittance to indicate normal platelet function, 50-69% mild dysfunction, 40-49% moderate dysfunction, whilst less than 40% indicated severe dysfunction. They found that markedly abnormal LTA ( < 40% light transmittance) accurately predicted patients requiring multiple transfusions. We demonstrated a good correlation between Thromboelastography(TEG) Platelet MappingTM and LTA at our institution(2) and have established perioperative TEGPlatelet MappingTM as a routine service for patients presenting for surgery who have failed to omit their anitplatelet medication . Based on the current evidence we chose a conservative value of < 30% platelet inhibition as being safe to proceed with surgery. Since the institution of this service we have avoided cancellation/postponement of surgery in 85% patients who might otherwise have been due to their recent ingestion of antiplatelet drugs. In addition TEGPlatelet MappingTM has enabled us to administer informed rather than empirical platelet transfusions in both elective and emergency patients. Recent ingestion of antiplatelet drugs by patients preoperatively poses a dilemma for the anaesthetist as to whether to proceed with surgery or not. One needs to consider the bleeding risk, the great inter-individual variation in response to antiplatelet agents, that there are a significant proportion of patients who exhibit resistance, in addition to the fact that no consensus exists on the timing of surgery after the withdrawal of these drugs. Therefore in response to the final question raised by the authors as to the usefulness of TEGPlatelet MappingTM to the anaesthetist, we would like to state that we believe, that by allowing rapid quantification of an individuals response to antiplatelet agents, TEGPlatelet MappingTM to be a very useful perioperative tool;which in our institution has led to improved patient care and financial savings in terms of reduced surgical cancellation. References 1: Agarwal S, Coakley M, Reddy K, Riddell A, Mallett S. Quantifying the effect of antiplatelet therapy: a comparison of the platelet function analyzer( PFA- 100) and modified thromboelastography(mTEG) with light transmission platelet aggregometry. Anaestheisology 2006; 105: 676-83 2: Chen et al. Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting. J Thorac Cardiovasc Surg 2004; 128: 425- 31 Conflict of Interest:None declared |
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