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Multicenter Study
. 2023 Sep;21(9):2596-2610.
doi: 10.1016/j.jtha.2023.05.027. Epub 2023 Jun 16.

Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology

Marie-Christine Alessi  1 , Carmen Coxon  2 , Manal Ibrahim-Kosta  3 , Monica Bacci  4 , Sophie Voisin  5 , José Rivera  6 , Andreas Greinacher  7 , Johannes Raster  7 , Fabio Pulcinelli  8 , Katrien M J Devreese  9 , Francois Mullier  10 , Aine N McCormick  11 , Juan Pablo Frontroth  12 , Claire Pouplard  13 , Ulrich J Sachs  14 , Isabelle Diaz  15 , Nuria Bermejo  16 , Marina Camera  17 , Pierre Fontana  18 , Anne Bauters  19 , Alain Stepanian  20 , Maria R Cozzi  21 , Anastasia N Sveshnikova  22 , Dorothée Faille  23 , Wendy Hollon  24 , Meera Chitlur  25 , Alessandra Casonato  26 , Dominique Lasne  27 , Cécile Lavenu-Bombled  28 , Mathieu Fiore  29 , Bello Hamidou  3 , Marie-Francoise Hurtaud-Roux  30 , Paul Saultier  3 , Louisa Goumidi  3 , Paolo Gresele  31 , Marie Lordkipanidzé  32
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Free article
Multicenter Study

Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology

Marie-Christine Alessi et al. J Thromb Haemost. 2023 Sep.
Free article

Abstract

Background: Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization.

Objectives: The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility. The secondary objective was to evaluate interindividual variability of results to appreciate the distribution of normal values and consequently better interpret pathologic results.

Methods: An international multicenter study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator that we supplied.

Results: We report variability in the potency (P) of activators in comparison with the comparator. Thrombin receptor activating peptide 6 (P, 1.32-2.68), arachidonic acid (P, 0.87-1.43), and epinephrine (P, 0.97-1.34) showed the greatest variability. ADP (P, 1.04-1.20) and ristocetin (P, 0.98-1.07) were the most consistent. The data highlighted clear interindividual variability, notably for ADP and epinephrine. Four profiles of responses were observed with ADP from high-responders, intermediate-responders, and low-responders. A fifth profile corresponding to nonresponders (5% of the individuals) was observed with epinephrine.

Conclusion: Based on these data, the establishment and adoption of simple standardization principles should mitigate variability due to activator sources. The observation of huge interindividual variability for certain concentrations of activators should lead to a cautious interpretation before reporting a result as abnormal. Confidence can be taken from the fact that difference between sources is not exacerbated in patients treated with antiplatelet agents.

Keywords: activators; aggregation; multicenter; platelets; standardization.

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Conflict of interest statement

Declaration of competing interests M.L. has received speaker fees from Bayer, participated in industry-funded trials from Idorsia, served on advisory boards for Servier and JAMP/Orimed Pharma, and received in-kind support for investigator-initiated grants from Fujimori Kogyo. M.C.A. has received fees from Novo Nordisk, participated in industry-funded trials from Agrobio, participated in PIA-funded project in collaboration with Stago and Agrobio, and served on advisory boards for Novo Nordisk. U.J.S. has received research grants from Octapharma; consulting fees from Bayer, SOBI, CSL Behring, and Pfizer; and travel support from Bayer, SOBI, CSL Behring, Biotest, Takeda, and Leo Pharma. D.F. has received honorarium and travel support from Viatris. S.V. has received travel support from Stago. F.M. has received speaker fees from Fresenius, Technoclone, and Werfen. P.F. has received travel support from SOBI and Novo Nordisk. A.G. reports personal fees from Aspen, Bayer Vital, Chromatec, Instrumentation Laboratory, Portola, Sanofi-Aventis, Roche, and GTH e.V.; grants from Ergomed, Boehringer Ingelheim, Rovi, Sagent, Biokit, Fa. Blau Farmaceutics, Prosensa/Biomarin, DRK-BSD Baden-Würtemberg/Hessen, Deutsche Forschungsgemeinschaft, Robert-Koch-Institut, Dilaflor, and GIZ Else-Körner-Stiftung; grants and personal fees from Macopharma; grants and other fee from DRK-BSD NSTOB; and nonfinancial support from Veralox, Vakzine Projekt Management GmbH, AstraZeneca, and Janssen Vaccines & Prevention B.V. outside the submitted work. In addition, A.G. has a patent—screening methods for transfusion-related acute lung injury (TRALI)—with royalties paid to EP2321644, 18.05.2011. M.C. has received research grant from Agios Pharmaceuticals, Genentech Inc, and Novartis Inc; consulting fees from Novo Nordisk; and honoraria for board participation with Novo Nordisk, Takeda Inc, Genentech Inc, BPL Inc, CSL Behring Inc, and Genzyme Corp Agios Pharmaceuticals. C.P. has received research grant from Stago. I.D. has received travel support from Sobi, Takeda, and Novonordisk and speaker fees from Novonordisk. A.B. has received fees from Aguettant, Alexion, and Viatris. J.R. has received support from Instituto de Salud Carlos (PI20/00926 [ISCIII&Feder], PMP21/00052 [ISCIII&NG EU], and CB15/00055) and Sociedad Española de Trombosis y Hemostasia (Ayuda a Grupo Español de Alteraciones Plaquetarias Congénitas). P.G. has received speaker’s fees from Sanofi and Roche, and honoraria for board participation with Viatris. M.R.C., M.C., C.L.-B., M.I.K., L.G., B.H., A.S., C.C., A.N.S., M.B., M.F., K.D., W.H., M.F.H., A.N.M., J.P.F., P.S., F.P., A.C., N.B., J.R., and D.L. have no conflict of interest to declare.

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