Background: Platelet transfusions are effective for the prevention and treatment of bleeding in patients with disorders of platelet number and/or function. In recent years plateletpheresis concentrates have outnumbered pooled platelet concentrates, albeit with significant differences between nations. Thus, the platelet quality of individual donors has become increasingly important. The aim of this study was to gain an estimate for the prevalence of unpaired platelet function among platelet donors. Study design and methods: We determined the interdonor variability in platelet plug formation with a PFA-100 analyzer, the prevalence of impaired thromboxane formation, and effects of the density, in alpha2 integrin polymorphism and density, Results: (i) Collagen-epinephrine induced closure time (CEPI-CT) showed a great inter-subject variability in platelet donors and was higher than in healthy controls (P = 0.008). One-fifth of donors had abnormal CEPI-CT values and 11% exceeded > 300 s (max measurable value). (ii) Decreased serum thromboxane B-2 levels were found in 9%. of all donors, compatible with surreptitious intake of cyclooxygenase inhibitors or with an aspirin-like, defect. CEPI-CT correlated inversely with TxB(2)-levels in donors and controls. (iii) The density of the alpha,integrin correlated negatively with CEPI-CT and CADP-CT values in controls, but was not responsible for the observed impaired platelet function in donors. (iv) Finally, the ABO blood group system modulates closure times. Conclusion: In sum, a large number of platelet donors present with prolonged closure time,. Decreased thromboxane formation and frequent platelet donation partly account for this observation.