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Both the High Affinity Thrombin Receptor (GPIb-IX-V) and GPIIb/IIIa Are Implicated in Expression of Thrombin-induced Platelet Procoagulant Activity

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2001: 86/4 (Oct) pp.939-1135
Pages: 1065-1069

Both the High Affinity Thrombin Receptor (GPIb-IX-V) and GPIIb/IIIa Are Implicated in Expression of Thrombin-induced Platelet Procoagulant Activity

Ira B. Dicker (1), Donna L. Pedicord(1), Dietmar A. Seiffert(1), G.A. Jamieson(2), Nicholas J. Greco(2)
(1)DuPont Pharmaceuticals Company, Wilmington, DE and (2)American Red Cross, Rockville, MD, USA

Summary

Platelets activated by α-thrombin express surface procoagulant activity (PCA) that accelerates the conversion of prothrombin to α-thrombin. Following activation with 10 nM α-thrombin, the PCA of normal platelets was approximately five-fold higher than that of Bernard-Soulier platelets (lacking GPIb). Normal platelet PCA was inhibited ~50 % by activation in the presence of the anti-GPIb MoAbs LJIb10 or TM60. Moreover, normal platelet PCA was completely abrogated in the presence of a combination of both LJIb10 and c7E3, a MoAb directed against αIibβ3 (GPIIb/IIIa). In contrast, PCA expressed by Bernard Soulier or Glanzmann platelets was not inhibited by either LJIb10 or c7E3 MoAb. The platelet activating peptide SFLLRN at 10 µM, a concentration which fully activates platelet aggregation and Ca2+ mobilization, generated PCA activity one fifth of that generated by α-thrombin at 10 nM but anti-PAR1 antibodies did not affect thrombininduced PCA expression. These results demonstrate that GPIb mediates, at least in part, the thrombin-induced activation of platelets that leads to PCA, and that αIibβ3 is also involved in PCA generation, but these results do not support a major role for PAR1 in this activation.