Platelet function testing and resistance in vascular surgery: a reply

We thank Xu et al. [1] for their appraisal of our PLUGS study [2] and welcome the opportunity to clarify the relevant aspects of our work. First, we acknowledge that the prevalence of clopidogrel resistance will vary considerably according to the assays and thresholds used. As highlighted by the authors, there is no gold standard that is accepted universally for defining clinically meaningful platelet inhibition in the peri-operative setting. Our intention was not to establish a definitive prevalence of pharmacodynamic resistance, but rather to characterise platelet function prospectively in a contemporary vascular surgical cohort using a commonly available near-patient assay. Second, we agree that the subgroup analysis evaluating platelet function before and after clopidogrel cessation was exploratory and limited by small sample size. We concur that the absence of substantial change in TEG 6s parameters in those patients may reflect low baseline platelet inhibition rather than failure of recovery per se. Our conclusions were, therefore, intentionally cautious and hypothesis-generating. We did not intend to suggest that guideline-recommended discontinuation intervals are ineffective universally, but rather that recovery trajectories may be heterogeneous and not fully captured by fixed time-based approaches alone. We also agree that the observed association between thrombotic complications, elevated von Willebrand factor concentrations and reduced platelet inhibition should be interpreted cautiously. Our study was neither designed nor powered to establish causal mechanistic relationships. As discussed in the manuscript, these findings are preliminary and serve primarily to support further investigation into the interaction between platelet reactivity, endothelial activation and thrombotic risk in patients undergoing vascular surgery. We agree that incorporation of complementary assays, pharmacogenomic testing and larger multicentre datasets would strengthen future work in this area. Lastly, we concur fully that platelet function data alone are insufficient to guide peri-neuraxial decision-making, although this approach has been described in case series [3, 4]. Definitive prospective studies evaluating rare but catastrophic complications, such as neuraxial haematoma, are unlikely to be feasible in practice given the very low event rate. Consequently, many aspects of peri-operative antiplatelet management for neuraxial anaesthesia will inevitably continue to rely on imperfect evidence, expert consensus and biological plausibility rather than adequately powered randomised trials alone [5]. Within this context, the aim of PLUGS was to provide initial, pragmatic, prospective data highlighting the marked interindividual variability in platelet function within a high-risk surgical cohort, while also helping to inform future research and clinical decision-making regarding the role of platelet function testing in patients undergoing vascular surgery.