Abstract
Assessment of platelet secretion is crucial for diagnosing suspected inherited platelet function disorders (IPFD). A previous survey of the SSC on Platelet Physiology of the ISTH and a comprehensive review highlighted that most of the platelet secretion assays (PSA) lack standardization and validation. The aim of this study was to provide expert consensus guidance on the use of PSAs for IPFD diagnosis.
We surveyed 26 experts from 10 different countries using the RAND/UCLA methodology, to attain a consensus on sensitivity, specificity, feasibility, time to readout and cost of most PSAs. Answers were then graded in 3 categories: appropriate, uncertain, and inappropriate. Equivocal or misinterpretable statements required a second and third round survey involving 14 of the original 26 experts. We report here the consolidated results of the entire procedure.
There was uniform agreement on several general statements, including that PSAs should be performed in hemostasis laboratories as first line diagnostic tests even in patients with normal platelet aggregation, and should include a δ-granule secretion marker. Among the specific assays examined, lumiaggregometry, other luciferin/luciferase-based assays, HPLC-methods, radiolabelled-serotonin based assays and whole-mount transmission electron microscopy were rated as appropriate for the measurement of δ-granule release, and platelet P-selectin expression by flow cytometry and released proteins by ELISA for α-granule release. For most of the other PSAs, the expert opinions were widely dispersed.
Lack of expert consensus on many PSAs indicates clearly an unmet need for rigorous standardization, multicentre comparison of results and validation of PSAs for clinical laboratory practice.
We surveyed 26 experts from 10 different countries using the RAND/UCLA methodology, to attain a consensus on sensitivity, specificity, feasibility, time to readout and cost of most PSAs. Answers were then graded in 3 categories: appropriate, uncertain, and inappropriate. Equivocal or misinterpretable statements required a second and third round survey involving 14 of the original 26 experts. We report here the consolidated results of the entire procedure.
There was uniform agreement on several general statements, including that PSAs should be performed in hemostasis laboratories as first line diagnostic tests even in patients with normal platelet aggregation, and should include a δ-granule secretion marker. Among the specific assays examined, lumiaggregometry, other luciferin/luciferase-based assays, HPLC-methods, radiolabelled-serotonin based assays and whole-mount transmission electron microscopy were rated as appropriate for the measurement of δ-granule release, and platelet P-selectin expression by flow cytometry and released proteins by ELISA for α-granule release. For most of the other PSAs, the expert opinions were widely dispersed.
Lack of expert consensus on many PSAs indicates clearly an unmet need for rigorous standardization, multicentre comparison of results and validation of PSAs for clinical laboratory practice.
| Original language | English |
|---|---|
| Pages (from-to) | 2127-2135 |
| Journal | Journal of Thrombosis and Haemostasis |
| Volume | 20 |
| Issue number | 9 |
| Early online date | 8 Jun 2022 |
| DOIs | |
| Publication status | E-pub ahead of print - 8 Jun 2022 |
Keywords
- Expert consensus
- Inherited platelet disorders
- Platelet Secretion
- Platelet function
- Platelet granules
- Platelet release reaction