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Thiazole orange : a complement to established methods for diagnosing inherited dense granule defects

Martin, Myriam LU orcid ; Strandberg, Karin LU ; Zetterberg, Eva LU and Norström, Eva LU (2025) In Platelets 36(1).
Abstract

What is the context?: Platelets contain three major types of granules (alpha granules, dense granules and lysosomal granules) that carry distinct cargo. Dense granules store small molecules such as calcium, serotonin and adenosine 5′-diphosphate (ADP) that are essential for platelet activation and aggregation. Impaired production or release of dense granules can affect blood clotting and cause increased bleeding, known as platelet granule disorders. These deficiencies are heterogeneous, rare and likely underdiagnosed due to the lack of easily accessible methods. What is new?: In this study, we explore the potential of thiazole orange as novel diagnostic marker for dense granule defects. Thiazole orange is a fluorescent dye commonly used... (More)

What is the context?: Platelets contain three major types of granules (alpha granules, dense granules and lysosomal granules) that carry distinct cargo. Dense granules store small molecules such as calcium, serotonin and adenosine 5′-diphosphate (ADP) that are essential for platelet activation and aggregation. Impaired production or release of dense granules can affect blood clotting and cause increased bleeding, known as platelet granule disorders. These deficiencies are heterogeneous, rare and likely underdiagnosed due to the lack of easily accessible methods. What is new?: In this study, we explore the potential of thiazole orange as novel diagnostic marker for dense granule defects. Thiazole orange is a fluorescent dye commonly used to mark immature red blood cells. At low concentration it also marks immature platelets due to its RNA-binding properties. However, at high concentrations, thiazole orange produces a stronger signal in platelets by binding to ADP in dense granules. Compared to mepacrine, a well-established dense granule marker, thiazole orange demonstrated superior detection of dense granules. Reduction of the signal upon platelet activation confirmed suitability even as marker for release defects. What is the impact?: Thiazole orange confirmed dense granule deficiency/release defects in patient samples and indicated that even more cases might be detected than with routinely used methods. The proposed thiazole orange method can easily be implemented in specialist coagulation laboratories and may provide enhanced sensitivity for the diagnosis of dense granule defects.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dense granules, flow cytometric activation assay, inherited platelet disorder, light transmission aggregometry, platelet granule defects, thiazole orange
in
Platelets
volume
36
issue
1
article number
2592683
publisher
Taylor & Francis
external identifiers
  • pmid:41324304
  • scopus:105023452867
ISSN
0953-7104
DOI
10.1080/09537104.2025.2592683
language
English
LU publication?
yes
id
5dc11dd7-562e-4586-85b2-05b09218c57c
date added to LUP
2026-02-03 17:00:33
date last changed
2026-02-03 17:01:00
@article{5dc11dd7-562e-4586-85b2-05b09218c57c,
  abstract     = {{<p>What is the context?: Platelets contain three major types of granules (alpha granules, dense granules and lysosomal granules) that carry distinct cargo. Dense granules store small molecules such as calcium, serotonin and adenosine 5′-diphosphate (ADP) that are essential for platelet activation and aggregation. Impaired production or release of dense granules can affect blood clotting and cause increased bleeding, known as platelet granule disorders. These deficiencies are heterogeneous, rare and likely underdiagnosed due to the lack of easily accessible methods. What is new?: In this study, we explore the potential of thiazole orange as novel diagnostic marker for dense granule defects. Thiazole orange is a fluorescent dye commonly used to mark immature red blood cells. At low concentration it also marks immature platelets due to its RNA-binding properties. However, at high concentrations, thiazole orange produces a stronger signal in platelets by binding to ADP in dense granules. Compared to mepacrine, a well-established dense granule marker, thiazole orange demonstrated superior detection of dense granules. Reduction of the signal upon platelet activation confirmed suitability even as marker for release defects. What is the impact?: Thiazole orange confirmed dense granule deficiency/release defects in patient samples and indicated that even more cases might be detected than with routinely used methods. The proposed thiazole orange method can easily be implemented in specialist coagulation laboratories and may provide enhanced sensitivity for the diagnosis of dense granule defects.</p>}},
  author       = {{Martin, Myriam and Strandberg, Karin and Zetterberg, Eva and Norström, Eva}},
  issn         = {{0953-7104}},
  keywords     = {{Dense granules; flow cytometric activation assay; inherited platelet disorder; light transmission aggregometry; platelet granule defects; thiazole orange}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Taylor & Francis}},
  series       = {{Platelets}},
  title        = {{Thiazole orange : a complement to established methods for diagnosing inherited dense granule defects}},
  url          = {{http://dx.doi.org/10.1080/09537104.2025.2592683}},
  doi          = {{10.1080/09537104.2025.2592683}},
  volume       = {{36}},
  year         = {{2025}},
}