Development and validation of an in vitro model to study thrombin generation on the surface of catheters in platelet-poor and platelet-rich plasma.

Coagulation activation on medical devices remains a significant problem as it can lead to dramatic thromboembolic complications. Understanding its poorly described mechanisms and finding optimal pharmacological prevention means is crucial to improve patient safety. We developed an in vitro model to study thrombin generation (TG) initiated by the contact of plasma with the surface of catheters. Interventional cardiology catheters were cut into segments and inserted in the bottom of multi-well plates; TG was then measured with the calibrated automated thrombogram (CAT). Model performance (analytical, intra- and inter-individual variability) was investigated and compared with activation of thrombin generation by tissue factor (TF) or contact pathway activator (ellagic acid), in the presence (PRP) and absence (PPP) of platelets. Model response to unfractionated heparin (UFH) was also assessed. TG was greater when measured in presence of catheter segments, compared to conditions without activators. The analytical variability of the model was good (CV ≤ 5 %), both with PPP and PRP. Intra-individual variability was between 15 and 30 % with PPP and between 10 and 15 % with PRP. Inter-individual variability was between 15 and 30 % with both kinds of plasma samples. The analytical performance of the catheter-initiated TG model was equivalent to that observed when TG was initiated with TF or ellagic acid. Catheter-initiated TG was measurable until 0.1 IU/mL UFH with PPP and until 1.0 IU/mL UFH with PRP, highlighting the crucial requirement of platelets. Our model is suitable for studying TG initiated with catheters. Inhibition of TG by UFH is overestimated in the absence of platelets.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael hardy reports financial support was provided by Fund for Scientific Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest MH, BR, OX, SL, TL: none. JD is the CEO and founder of QUALIblood s.a., a contract research organization manufacturing the DP-Filter, is a coinventor of the DP-Filter (patent application number: PCT/ET2019/052903) and reports personal fees from Daiichi-Sankyo, Mithra Pharmaceuticals, Diagnostica Stago, Roche and Roche Diagnostics, outside the submitted work. FM reports institutional fees from Stago, Werfen, Nodia, Roche Sysmex and Bayer. He also reports speaker fees from Boehringer-Ingelheim, Bayer Healthcare, Bristol-Myers Squibb-Pfizer, Diagnostica Stago, Sysmex and Aspen, all outside the submitted work.