Expert opinion on the use of platelet secretion assay for the diagnosis of inherited platelet function disorders: communication from the ISTH SSC Subcommittee on platelet physiology

Diego Mezzano, Paul Harrison, III Andrew L. Frelinger, Andrew D. Mumford, Patrizia Noris, Marie Lordkipanidzé, Paolo Gresele

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalJournal of Thrombosis and Haemostasis
Early online date8 Jun 2022
DOIs
Publication statusE-pub ahead of print - 8 Jun 2022

Keywords

  • Expert consensus
  • Inherited platelet disorders
  • Platelet function
  • Platelet granules
  • Platelet release reaction
  • Platelet Secretion

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