Diabetes Type 2: Circulating Phosphatidylserine-Expressing Platelets Regulate Whole Blood Agonist-Evoked Platelet Activity In Vitro

Background Platelet agonists responses in vitro (i.e., reactivity) include the creation of phosphatidylserine (PS)-exposing platelets together with the activation of the fibrinogen receptors (αIIbβ3) and lysosomal exocytosis. It is feasible to judge the activation pathways by analyzing platelet surface annexin V, the activated fibrinogen receptor (PAC-1), and the release of lysosomal-associated membrane protein (LAMP-1), correspondingly. We postulate that, in type 2 diabetes (T2DM), surface PS of circulating platelets, unprovoked in vitro, links with whole blood (WB) agonist-induced responses. Patients and Methods After informed consent, T2DM subjects (n = 35) were enrolled. A Percoll gradient (1.09–1.04 kg/L) separated their normal-sized platelets according to density into subpopulations (n = 8). A flow cytometer analyzed surface annexin V (mean fluorescence intensity [MFI]) of the subfractions, unprovoked ex vivo. The datasets were subsequently correlated with platelet WB agonist-induced responses (i.e., annexin V, PAC-1, and LAMP-1 [all MFI]) to α-thrombin (10 μM), cross-linked collagen-related peptide (CRP-XL, 0.15 μg/mL), and adenosine diphosphate (ADP, 5 μM) in vitro. Results Surface annexin V (MFI) of most platelet subfractions and the magnitudes of WB agonist-induced annexin V (MFI) of normal-sized platelets in vitro associated closely. Such PS-expressing platelets also linked inversely with WB agonist-evoked surface PAC-1 (MFI) (all used agonists) and LAMP-1 (MFI) (CRP-XL, ADP only). It is concluded that surface PS, unprovoked in vitro, of most density-separated platelets connected with platelet reactivity, i.e., their WB agonist-evoked reactions in the test tube.