HPA-1 polymorphism of αIIbβ3 modulates platelet adhesion onto immobilized fibrinogen in an in-vitro flow system

Platelets in anticoagulated whole blood [49 healthy previously genotyped blood donors) were labelled with fluorescence dye and perfused through a rectangular flow chamber (shear rates of 50 s-1, 500 s-1 and 1500 s-1). A fluorescence laser-scan microscope was used for visualisation and quantification of platelet adhesion at 15 sec, 1 and 5 minutes after start of perfusion.During perfusion, the platelet adhesion linearly increased with regard to exposition time and shear rate. Perfusion of blood preincubated with Abciximab over fibrinogen-coated cover-slips showed reduced platelet adherence (absolute fluorescence: 168 ± 35 U vs. 53000 ± 19000 at control experiments, p < 0.05), as well as by perfusion over BSA-coated glass coverslips. Platelet with HPA-1a/1a genotype exhibited initial better adhesion but they also exhibited higher detachment under arterial flow conditions compared to the HPA-1b/1b platelets. Analysis of stable adhesion rate indicate that the platelets carrying the HPA-1b/1b genotype have a higher reactivity threshold for initial interaction with fibrinogen but under the higher shear rate (in regard to time of perfusion) also realize more stable bonds with fibrinogen than platelets with the HPA-1a/1a genotype.Our data support the contention that genetically determined variants of platelet integrins αIIbβ3 could play a role in arterial thrombogenesis and thus confirm the hypothesis derived from epidemiological studies.A platelet-dependent process is the underlying mechanism of arterial thrombosis, and the critical role of platelets in this process is now widely accepted [1,2]. Participation of platelets in arterial thrombosis is centered on the platelet's adhesive properties and the ability to respond to stimuli with rapid activation and, in turn, aggregation [2] – the same features that support the arrest of bleeding from wounds. The normal function of platelets is, however, to arrest bleeding from wounds, which requires adhesion to altered vascular sur