The impact of enhanced platelet turnover on platelet reactivity in healthy humans

Introduction Platelet turnover describes the process of platelet generation and clearance. We recently showed that a routine double platelet apheresis can enhance platelet turnover. The increase of platelet count after apheresis is associated with a transient increase of young, reticulated platelets in the circulation. Therefore, we aimed to investigate, how the increase of young platelets influences platelet function.

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

Results Platelet count recovery from day 0 after apheresis to day 3 was compared between platelet donors. Five out of 15 individuals showed a platelet count recovery above 20% of platelet count after platelet depletion (rapid turnover). Whereas the other platelet donors showed a slower platelet count recovery until day 3, followed by a stronger platelet count increase after three days (slow turnover). Response to agonists was significantly increased in rapid turnover donors: In comparision to day 0 (baseline) the PAC-1-binding was significantly increased on day 3 after stimulation with TRAP-6 (MFI 4,172 vs 5,951, p=0.016) and CRP (MFI 5,420 vs 7,769, p= 0.0125). Comparable results have been 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 of platelet reactivity could be detected in donors with slow turnover.

Conclusion The increase of platelet turnover after apheresis is donor dependent. Subjects with a rapid turnover show a transient increase of platelet reactivity whereas no dynamic in platelet function is present 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.

 

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Conflict of Interest

No conflict of interest to disclose.

Publication History

Article published online:
20 February 2023