δ-granule deficiency in patients with sepsis or COVID-19. Characteristics of healthy control participants (ctrl), patients with infection (inf), sepsis, or COVID-19 are displayed on hospital/ICU admission day (t1) and days 4 to 7 (t2). (A-E) Schematic visualization of mepacrine assay depicted in panel A. Mepacrine uptake (C) and release (D) upon TRAP-6 stimulation (5 μM) were quantified in whole blood using flow cytometry. (E) Relative (rel.) mepacrine release was determined by calculating the relation of mepacrine uptake/release. (F-G) Adenosine triphosphate (ATP) release upon TRAP-6 stimulation (10 μM) was determined in platelet-rich plasma by lumiaggregometry (minimal platelet count > 150/nL). (H-I) Number of δ-granules was determined in platelet-rich plasma using WM-TEM. (H) Representative images are shown, red arrows indicate δ-granules. Scale bars indicate 1 μm. (I) Dots show median δ-granule number per platelet calculated in a 2 investigator–blinded approach. Representative figures are displayed in panels B, F, and H. All graphs show median ± 95% CI. Differences were analyzed using the Kruskal-Wallis test. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001.
