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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:919-924.)
© 1997 American Heart Association, Inc.

Articles

Relative Involvement of GPIb/IX-vWF Axis and GPIIb/IIIa in Thrombus Growth at High Shear Rates in the Guinea Pig

Patrick André; Patricia Hainaud; Claire Bal dit Sollier; Leonard I. Garfinkel; Jacques P. Caen; ; Ludovic O. Drouet

From the INSERM U353 (P.A., L.O.D.); the Institut des Vaisseaux et du Sang (P.A., P.H., C.B. dit S., J.P.C., L.O.D.), Paris, France; and the Biotechnology General Ltd, Rehovot, Israel (L.I.G.).

Correspondence to Patrick André, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, 8 rue Guy Patin, 75475 Paris Cedex 10, France.

Abstract The relative involvement of the glycoprotein (GP) Ib/IX–von Willebrand factor (vWF) axis and GPIIb/IIIa in thrombus growth at high shear rates was assessed and compared by testing the pharmacological effects of VCL, a recombinant GPIb-binding fragment of vWF (residues 504-728), aurintricarboxylic acid (ATA), which binds to the 509-695 disulfide loop of vWF, and lamifiban, a specific synthetic GPIIb/IIIa antagonist. In vivo, their effects were evaluated in guinea pig mesenteric arteries, in a model of a laser-induced cyclic thrombotic process, and ex vivo, at a shear rate of 1800 s^-1, in a capillary perfusion chamber model, in which collagen-adherent platelets are exposed to nonanticoagulated guinea pig blood. In vivo, VCL, ATA, and lamifiban administered 2 minutes after intimal injuries stopped thrombus growth, prevented the cyclic thrombotic process, and induced gradual thrombus dissolution. Ex vivo, at 1800 s^-1, collagen exposure to untreated blood for 2 minutes, 4 minutes, or two consecutive periods of 2 minutes each resulted in similar platelet adhesion, 56%, 59%, and 61%, respectively, with an average thrombus volume of 6, 19, and 17.5 µm³/µm², respectively, without any fibrin formation. This indicated that the two consecutive perfusions did not affect the dynamic process of thrombus growth. When collagen-adherent platelets deposited after the first 2-minute perfusion were perfused for 2 minutes with VCL-, ATA-, or lamifiban-treated blood, thrombus growth was prevented and platelet adhesion remained unchanged, but fibrin formation increased on and around the predeposited platelets. These results suggest that both the GPIb/IX-vWF axis and GPIIb/IIIa are involved in in vivo platelet-to-platelet interactions at high shear rates in the guinea pig.

Key Words: thrombus • von Willebrand factor • GPIb/IX • GPIIb/IIIa

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