Aggregation and ATP secretion in a participant diagnosed with a dense granule defect. (A) Aggregation in a participant diagnosed with a defect in dense granule secretion on the basis of a significantly reduced level of secretion to high concentrations of PAR-1–specific peptide and other platelet agonists, including PAR-4–specific peptide and CRP relative to a panel of controls. “c” indicates control (healthy volunteer). The pattern of aggregation is representative of other participants diagnosed with a secretion disorder. (B) ATP secretion was measured alongside aggregation in a Born lumi-aggregometer in PRP using Chrono-Lume reagent for the detection of ATP. The degree of ATP secretion (after normalization to platelet count, supplemental Figure 2) to PAR-1–specific peptide (100μM) in healthy volunteers and participants diagnosed with defective dense granule secretion is shown. Participants identified with mutations in the P2Y₁₂ (present study), TxA₂ receptors,¹⁰  and HPS-8¹⁹  are identified by square brackets.