PB0891 - Impact of enhanced platelet turnover on platelet reactivity in healthy humans

Background: Platelet turnover describes the process of platelet generation and clearance. We recently showed that a double platelet apheresis can enhance platelet turnover, accompanied by a transient increase of young, reticulated platelets.

Aims: We investigate the effect of an increased young platelet population on platelet function in healthy humans.

Methods: Blood from platelet apheresis donors (n=15) was drawn on day 0 before apheresis, immediately after apheresis and on day 3 and 10. Intensity of platelet turnover was stratified by the extent of platelet count recovery until day 3. Platelet reactivity was determined after stimulation with TRAP-6 (thrombin-receptor-activating-peptide) and CRP (collagen-related-peptide) assessing CD62P-expression (alpha granule release) and PAC-1 binding (integrin αIIbβ3 activation). Mean fluorescence intensity (MFI) was measured by flow cytometry.

Results: Five out of 15 individuals showed a rapid turnover with a platelet count recovery above 20% from the nadir immediately after apheresis to day 3. Whereas the other platelet donors showed a slower platelet count recovery until day 3, followed by a stronger increase after three days (slow turnover). Platelet reactivity was increased in rapid turnover donors: Compared to day 0 the PAC-1-binding was increased on day 3 upon stimulation with TRAP-6 (MFI 4,172 vs 5,951, p=0.016) and CRP (MFI 5,420 vs 7,769, p=0.0125). Similar results were obtained for CD62P-expression after stimulation with CRP (MFI 28,444 vs 58,135, p=0.0274). Platelet reactivity returned to baseline values at day 10. No change was detected in donors with slow turnover.

Conclusion(s): The kinetic of platelet count recovery and reactivity after apheresis differed among donors. Subjects with rapid turnover show an increase of platelet reactivity whereas no dynamic in platelet function was observed in subjects with slow turnover. These findings implicate that platelet turnover influences platelet function in healthy individuals. This may have an impact on diseases associated with increased platelet turnover.