The First THROMKID-Plus Inter-laboratory Survey - Standardization and Quality Management of Platelet Light Transmission Aggregometry for the Diagnosis of Inherited Platelet Function Disorders in German-speaking Countries

Objectives: A variety of global and specific in vitro platelet function tests are available for the diagnosis of inherited platelet function disorders. Currently, the analyses of the blood count, stained blood smears and the light transmission aggregometry (LTA) according to Born are recommended as first-step tests (Gresele P et al. 2015, JTH; Knöfler R et al. 2014, Hamostaseologie, updated 2018), which are available in most clinical centers. Although the LTA is accepted as a “gold standard” assay for the evaluation of platelet function, its standardization in the clinical practice is still challenging. The GTH-based THROMKID-Plus Study Group has proceeded with this challenging task to create standards and a quality management of the LTA for German-speaking specialized laboratories and centers and performed an inter-laboratory survey in Germany and Austria.

Methods: Five different platelet agonists (stable at 4°C) and their concentrations were selected according to the SSC/ISTH recommendations (Cattaneo M et al. JTH (2013)) and shipped to 15 specialied laboratories/centres in Germany and Austria from the Clinical Transfusion Medicine in Tübingen. Eight inductors for each three different sets (healthy control, simulated platelet function disorders) were analyzed in the APACT or PAP4/8 aggregometer using platelet-rich plasma of a healthy donor from each lab. In addition, own platelet agonists of each lab were tested in platelet-rich plasma from the same donor within the same day.

Results: Nine labs used the APACT aggregometer and showed very consistent data regarding the maximum percentage of aggregation induced by the tested agonists. Furthermore, all nine labs identified the differential diagnosis of the simulated platelet function disorders. Similar consistent data were obtained in the other labs using the PAP4/8 aggregometer with one exception, which was due to technical problems. In contrast, there was a high variability of the lab-own inductors regarding reagent type and concentrations, resulting accordingly in variable inter-laboratory interpretation of the LTA results.

Conclusions: The shipment of stable platelet agonists is suitable for an inter-laboratory survey of platelet light transmission aggregometry according to Born. However, there are still persistent needs for standardization of agonist reagents and their concentration ranges as well as for definition of reference ranges. The LTA inter-laboratory survey for PAP and Chronolog aggregometers are currently optimized. Regular LTA inter-laboratory surveys based on agonist shipment are planned and will be extended for additional German-speaking platelet labs.