Patients admitted for bleeding symptoms may have a longer platelet function analyzer (PFA) closure time without signs of von Willebrand disease or reduced platelet aggregation. For a study, researchers sought to find out if the patients had a shear-dependent platelet function impairment. Patients with a high bleeding score and a history of PFA prolongation were included in the study. Von Willebrand factor (VWF) and platelet function tests were done, as well as exome sequencing. A microfluidic investigation of shear-dependent collagen-induced whole-blood thrombosis development was carried out. Microfluidic experiments revealed considerably decreased platelet adhesion and thrombus formation characteristics in 14 PFA-only patients when compared to healthy volunteers. Lower integrin activation, phosphatidylserine exposure, and P-selectin expression were all associated with it.
VWF was identified as the key explanatory variable of PFA prolongation by principal components analysis, whereas conventional platelet aggregation explained the lower thrombus characteristics under shear. Conventional platelet aggregation was in the lowest normal range in 5 patients with significant microfluidic anomalies. There were no causative variations found in Mendelian genes known to cause bleeding or platelet abnormalities. In the patients, multiparameter assessment of whole-blood thrombus formation under shear reveals single or combined effects of low–normal VWF and low–normal platelet aggregation, indicating a shear-dependent platelet function impairment not revealed by static conventional hemostatic assays.