A rapid whole-blood adenosine triphosphate secretion test can be used to exclude platelet-dense granule deficiency
Minka Zivkovic 1),2); Roger E.G. Schutgens 1); Vossa van der Vegte 1),2); Janoek A. Lukasse 1),2); Mark Roest 3); Dana Huskens 3); Annick S. de Moor 1); Idske C.L. Kremer Hovinga 1); Rolf T. Urbanus 1),2).
1) Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
2) Circulatory Health Research Center, University Medical Center Utrecht, Utrecht, the Netherlands
3) Synapse Research Institute, Maastricht, the Netherlands
Abstract
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.