title: Thrombin-inducible platelet adhesion and regulation of the platelet seven-transmembrane thrombin receptor-1 (PAR-1): effects of unfractionated heparin and lepirudin.
abstract: Heparin may induce platelet activation and even heparin-induced thrombocytopenia. Lepirudin has been approved for HIT treatment. We speculated that lepirudin inhibits platelet function under high shear and the platelet thrombin receptor PAR-1 better than heparin. Thrombin-inducible platelet adherence under high shear conditions and the expression of PAR-1 were studied after samples from healthy donors were exposed in vitro to increasing concentrations of unfractionated heparin or lepirudin. Compared to baseline and to lepirudin, heparin induced platelet P-selectin expression (p = 0.04). Platelet adherence increased slightly in the presence of lepirudin, but not heparin (p = 0.04). Thrombin-inducible platelet aggregate formation and consecutive adherence under high shear conditions was inhibited by both anticoagulants (p = 0.004). Further, heparin and lepirudin inhibited thrombin-inducible cleavage and internalization of PAR-1 at a dosage of 1.0 U/ml and 1.6 microg/ml, respectively (p = 0.004). Thus, heparin and lepirudin inhibit thrombin-inducible platelet activation in vitro to a similar extent.
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology, 1090 Vienna, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Reiter
authors.forename: Beate
authors.initials: B
authors.lastname: Eichelberger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D019007:P-Selectin; D044463:Receptor, PAR-1; D011994:Recombinant Proteins; D006493:Heparin; D013917:Thrombin; C083544:lepirudin