Multi-center evaluation of light transmission platelet aggregation reagents: Communication from the ISTH SSC Subcommittee on Platelet Physiology

Light transmission aggregation (LTA) is used widely by the clinical and research communities. While it is a gold standard, there is a lack of inter-laboratory harmonization. The primary objective was to assess whether sources of activators (mainly Adenosine diphosphate (ADP), Collagen, Arachidonic acid, Epinephrine, Thrombin Receptor Activating Peptide (TRAP)6) 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 pathological results. International multi-center study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator which we supplied. We report a variability in the potency (P) of activators in comparison to the comparator. TRAP6 (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 response were observed with ADP from high responders, intermediate responders and low responders. A fifth profile corresponding to non-responders (5% of the individuals) was observed with epinephrine. On the basis of 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.