A rapid whole-blood adenosine triphosphate secretion test can be used to exclude platelet-dense granule deficiency

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.

Keywords: blood platelet disorder; diagnostic tests; luminescent assay; platelet function tests; platelet storage pool deficiency.