TY - JOUR
T1 - Multicenter evaluation of light transmission platelet aggregation reagents
T2 - communication from the ISTH SSC Subcommittee on Platelet Physiology
AU - Alessi, Marie Christine
AU - Coxon, Carmen
AU - Ibrahim-Kosta, Manal
AU - Bacci, Monica
AU - Voisin, Sophie
AU - Rivera, José
AU - Greinacher, Andreas
AU - Raster, Johannes
AU - Pulcinelli, Fabio
AU - Devreese, Katrien M.J.
AU - Mullier, Francois
AU - McCormick, Aine N.
AU - Frontroth, Juan Pablo
AU - Pouplard, Claire
AU - Sachs, Ulrich J.
AU - Diaz, Isabelle
AU - Bermejo, Nuria
AU - Camera, Marina
AU - Fontana, Pierre
AU - Bauters, Anne
AU - Stepanian, Alain
AU - Cozzi, Maria R.
AU - Sveshnikova, Anastasia N.
AU - Faille, Dorothée
AU - Hollon, Wendy
AU - Chitlur, Meera
AU - Casonato, Alessandra
AU - Lasne, Dominique
AU - Lavenu-Bombled, Cécile
AU - Fiore, Mathieu
AU - Hamidou, Bello
AU - Hurtaud-Roux, Marie Francoise
AU - Saultier, Paul
AU - Goumidi, Louisa
AU - Gresele, Paolo
AU - Lordkipanidzé, Marie
N1 - Funding Information:
This work was supported by a grant of the International Society for Thrombosis and Haemostasis, and in-kind by Diagnostica Stago (comparator reagents) and the National Institute for Biological Standards and Control (comparator reagents). The authors thank S. Ambard, Y. Katz, and E. Alvarez (C2VN, Inrae, Inserm, Aix Marseille Université, Marseille, France) for their help in sending the reagents to the different investigators and N. Saut, B. Bonardo, V. Sbarra, and E. Tomei (Laboratory of hematology, Centre de reference des pathologies plaquettaires, Marseille, France) for their help in preparing the aliquots of comparator.
Publisher Copyright:
© 2023 International Society on Thrombosis and Haemostasis
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - activators
KW - aggregation
KW - multicenter
KW - platelets
KW - standardization
UR - http://www.scopus.com/inward/record.url?scp=85164676171&partnerID=8YFLogxK
U2 - 10.1016/j.jtha.2023.05.027
DO - 10.1016/j.jtha.2023.05.027
M3 - Article
C2 - 37331519
AN - SCOPUS:85164676171
SN - 1538-7933
VL - 21
SP - 2596
EP - 2610
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 9
ER -