TY - JOUR
T1 - A rapid whole-blood adenosine triphosphate secretion test can be used to exclude platelet-dense granule deficiency
AU - Zivkovic, Minka
AU - Schutgens, Roger
AU - the SYMPHONY consortium
AU - TiN study group
AU - van der Vegte, Vossa
AU - Lukasse, Janoek A.
AU - Roest, Mark
AU - Huskens, Dana
AU - de Moor, Annick S.
AU - Kremer Hovinga, Idske C.L.
AU - Urbanus, Rolf T.
AU - van den Akker, Emile
AU - Al Arashi, Wala
AU - Arisz, Ryanne
AU - Baas, Lieke
AU - Bierings, Ruben
AU - van den Biggelaar, Maartje
AU - Boender, Johan
AU - van der Bom, Anske
AU - Bos, Mettine
AU - Brands, Martijn
AU - Bredenoord, Annelien
AU - Bukkems, Laura
AU - Burdorf, Lex
AU - Del Castillo Alferez, Jessica
AU - Cloesmeijer, Michael
AU - Cnossen, Marjon
AU - Driessens, Mariëtte
AU - Eikenboom, Jeroen
AU - Fijnvandraat, Karin
AU - Fischer, Kathelijn
AU - Goedhart, Tine
AU - Hazelzet, Jan
AU - van Hoorn, Shannon
AU - Huisman, Elise
AU - Jansen, Nathalie
AU - Kruip, Marieke
AU - Laan, Sebastiaan
AU - van Leeuwen, Nikki
AU - Lingsma, Hester
AU - de Maat, Moniek
AU - Meijer, Karina
AU - van Moort, Iris
AU - Mussert, Caroline
AU - Polinder, Suzanne
AU - Reitsma, Simone
AU - Romano, Lorenzo
AU - Schols, Saskia
AU - Uyl, Carin
AU - Zhang, Huan
AU - Zivkovic, Minka
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/5
Y1 - 2025/5
N2 - Background: Delta storage pool disease (δ-SPD) is a rare platelet function disorder (PFD) characterized by a deficiency of dense granules or defective granule secretion, leading to bleeding diathesis. Diagnostics of δ-SPD are difficult and lack standardization, leading to underestimation of its prevalence. Current diagnostic methods are based on granule content assays or lumi-aggregometry, which have limited availability. Therefore, there is an unmet need for a rapid, accessible test for δ-SPD. Objectives: To evaluate the diagnostic value of a rapid whole-blood adenosine triphosphate (ATP) secretion test for δ-SPD. Methods: ATP secretion after PAR-1 activating peptide (PAR-1 AP; TRAP-6) stimulation was assessed in whole blood using luminescence in 50 healthy controls, 22 patients with a suspected PFD other than storage pool disease (non-SPD) and 25 patients with δ-SPD and corrected for platelet count. Diagnostic value of the test was determined with C-statistics, sensitivity, specificity, likelihood ratios (LLRs), and predictive values (PVs). Results: PAR-1 AP mediated ATP secretion in the rapid test was lower in δ-SPD than in healthy controls and non-SPD patients (P < .0001). The rapid test was able to discriminate between δ-SPD and non-SPD patients (C-statistic 0.88; 95% CI, 0.78-0.98). At a cutoff value of the highest value of the δ-SPD group, the sensitivity was 100% and the specificity was 64%. This cutoff value corresponded with a positive LLR of 2.75, an optimal negative LLR of 0.00, positive PV of 76%, and negative PV of 100%. Conclusion: A whole-blood ATP secretion test can be used to exclude ẟ-SPD in patients presenting with a primary hemostasis defect.
AB - Background: Delta storage pool disease (δ-SPD) is a rare platelet function disorder (PFD) characterized by a deficiency of dense granules or defective granule secretion, leading to bleeding diathesis. Diagnostics of δ-SPD are difficult and lack standardization, leading to underestimation of its prevalence. Current diagnostic methods are based on granule content assays or lumi-aggregometry, which have limited availability. Therefore, there is an unmet need for a rapid, accessible test for δ-SPD. Objectives: To evaluate the diagnostic value of a rapid whole-blood adenosine triphosphate (ATP) secretion test for δ-SPD. Methods: ATP secretion after PAR-1 activating peptide (PAR-1 AP; TRAP-6) stimulation was assessed in whole blood using luminescence in 50 healthy controls, 22 patients with a suspected PFD other than storage pool disease (non-SPD) and 25 patients with δ-SPD and corrected for platelet count. Diagnostic value of the test was determined with C-statistics, sensitivity, specificity, likelihood ratios (LLRs), and predictive values (PVs). Results: PAR-1 AP mediated ATP secretion in the rapid test was lower in δ-SPD than in healthy controls and non-SPD patients (P < .0001). The rapid test was able to discriminate between δ-SPD and non-SPD patients (C-statistic 0.88; 95% CI, 0.78-0.98). At a cutoff value of the highest value of the δ-SPD group, the sensitivity was 100% and the specificity was 64%. This cutoff value corresponded with a positive LLR of 2.75, an optimal negative LLR of 0.00, positive PV of 76%, and negative PV of 100%. Conclusion: A whole-blood ATP secretion test can be used to exclude ẟ-SPD in patients presenting with a primary hemostasis defect.
UR - https://www.scopus.com/pages/publications/85219022624
U2 - 10.1016/j.jtha.2025.01.013
DO - 10.1016/j.jtha.2025.01.013
M3 - Article
C2 - 39938683
AN - SCOPUS:85219022624
SN - 1538-7933
VL - 23
SP - 1667
EP - 1675
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 5
ER -