Impaired surface receptor expression on immature platelets in bleeding patients with abnormal light transmission aggregometry.

Background: A platelet function defect (PFD) is diagnosed in patients with mild to moderate bleeding disorders (MBD) and abnormalities in light transmission aggregometry (LTA). The influence of platelet aging on platelet function in PFD remains unclear.

Methods: Twenty-two patients with LTA alterations from the Vienna Bleeding Biobank were compared to 19 age- and sex-matched healthy controls. Blood samples were immediately analyzed using PFA-100 with epinephrine cartridges. Platelets subtypes were characterized via surface receptor profiling of CD9, CD31, CD36, CD40L, CD42b, CD62P, CD63, CD107 and toll like receptors (TLRs) 2, 4 and 9 and immature (RNA-rich) platelets were quantified.

Results: Platelet counts, immature platelet fraction, and mean platelet volume, as well as other hemostatic parameters, did not differ between patients and controls, while patients demonstrated prolonged closure times (CT) on PFA-100. Principal component analysis highlighted distinct glycoprotein expression patterns between immature and mature platelets in both their resting state and after activation, in patients and healthy controls. In patients, immature platelets expressed lower levels of CD62P, CD36, CD31, TLR2, and TLR4, but increased TLR9 expression, while mature platelets showed no differences. These distinct surface receptor patterns of immature platelets were partly associated with reduced TRAP-6-induced platelet aggregation.

Conclusion: This study demonstrates significant alterations in surface receptor expression on immature platelets in patients with suspected PFD, underscoring immature platelets as crucial link to platelet biology and clinical symptoms in this patient population.