Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombon-induced platelet procoagulant activity

Platelets activated by alpha -thrombin express surface procoagulant activit y (PCA) that accelerates the conversion of prothrombin to alpha -thrombin. Following activation with 10 nM alpha -thrombin, the PCA of normal platelet s was approximately five-fold higher than that of Bernard-Soulier platelets (lacking GPIb). Normal platelet PCA was inhibited similar to 50 % by activ ation in the presence of the anti-GPIb MoAbs LJIb10 or TM60. Moreover, norm al platelet PCA was completely abrogated in the presence of a combination o f both LJIb10 and c7E3, a MoAb directed against alpha (IIb)beta (3) (GPIIb/ IIIa). In contrast, PCA expressed by Bernard Soulier or Glanzmann platelets was not inhibited by either LJIb10 or c7E3 MoAb. The platelet activating p eptide SFLLRN at 10 muM, a concentration which fully activates platelet agg regation and Ca2+ mobilization, generated PCA activity one fifth of that ge nerated by alpha -thrombin at 10 nM but anti-PAR1 antibodies did not affect thrombin-induced PCA expression, These results demonstrate that GPIb media tes, at least in part, the thrombin-induced activation of platelets that le ads to PCA, and that alpha (IIb)beta (3) is also involved in PCA generation , but these results do not support a major role for PAR1 in this activation .