The role of platelet membrane glycoproteins Ib and IIb-IIIa in platelet adherence to human artery subendothelium.
Platelet adherence to human artery subendothelium in blood from eight normal subjects, four patients with Glanzmann's thrombasthenia (deficiency of platelet membrane glycoproteins IIb and IIIa: GPIIb-IIIa), two patients with Bernard-Soulier syndrome (deficiency of platelet membrane glycoprotein Ib: GPIb) and one patient with von Willebrand's disease (VWD subtype III. deficient in factor VIII-von Willebrand factor: FVIII-VWF) was compared at various wall shear rates (300, 500, 1000, 1800 and 2500 s-1). Platelet adherence in blood from the patients with Glanzmann's thrombasthenia was within the normal range at shear rates below 1000 s-1. There was some decrease in adhesion at higher shear rates and platelets were less spread out on the subendothelium than normally at all shear rates. Platelet aggregate formation was almost totally absent. Platelet adherence in blood from patients with the Bernard-Soulier syndrome was strongly impaired at all shear rates. Platelet adherence in blood from the patient with VWD subtype III was normal at shear rates of 300 and 500 s-1, but impaired at shear rates above 1000 s-1. Aggregate formation was also decreased at these shear rates. Platelet adhesion was strongly inhibited by a monoclonal antibody against glycoprotein Ib, which had previously been shown to inhibit ristocetin-induced aggregation, at shear rates of 500 and 1800 s-1 but not at 300 s-1. Platelet adhesion at 1800 s-1 was also inhibited, though to a lesser extent, by two antibodies against GPIIb-IIIa. These antibodies also inhibited platelet aggregate formation. The data indicates that GPIb is involved in adhesion at the same shear rates as von Willebrand factor. Absence or inhibition of GPIIb-IIIa primarily causes a defect of aggregate formation but GPIIb-IIIa may also play a role in adhesion, particularly at high shear rates. The defect of adhesion in the Bernard-Soulier syndrome may be dependent on factors other than a deficiency of GPIb alone.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001158:Arteries / Q000503:physiopathology*; D001606:Bernard-Soulier Syndrome / Q000097:blood; D004727:Endothelium / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000172:deficiency* / Q000276:immunology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000276:immunology; D008875:Middle Aged; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D013915:Thrombasthenia / Q000097:blood; D014842:von Willebrand Diseases / Q000097:blood
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins